{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T04:46:12Z","timestamp":1782362772749,"version":"3.54.5"},"reference-count":111,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background\/Objectives: Non-small cell lung cancer (NSCLC) remains associated with high mortality, frequent late-stage diagnosis, biological heterogeneity, and recurrence after treatment. Although molecular and immunohistochemical biomarkers have transformed treatment selection, there remains a need for accessible, repeatable, and clinically practical circulating biomarkers that may support prognosis and post-treatment monitoring. This review discusses prolactin (PRL) as a candidate supplementary biomarker in NSCLC, with particular emphasis on its biological rationale, potential prognostic relevance, and possible role in personalized risk stratification after systemic therapy. Methods: This narrative review summarizes current evidence on established biomarkers in NSCLC, the physiology and regulation of PRL, PRL\/PRLR signaling in cancer biology, mechanisms of PRL dysregulation in lung cancer, and available clinical observations concerning PRL alterations in NSCLC. Particular attention is given to the distinction between prognostic and predictive biomarkers, longitudinal monitoring, pituitary involvement, immune checkpoint inhibitor-related endocrine effects, and biological, pharmacological, and analytical confounders affecting PRL interpretation. Results: Current evidence suggests that PRL may be biologically relevant in NSCLC through its involvement in pathways related to cell proliferation, survival, angiogenesis, invasion, epithelial\u2013mesenchymal transition, immune modulation, and possible therapy resistance. Clinical observations indicate that altered PRL levels may occur in advanced disease, pituitary involvement, systemic inflammation, stress, or during anticancer and supportive treatment. However, PRL lacks cancer specificity and is influenced by multiple confounders, including circadian rhythm, stress, endocrine disorders, macroprolactin, cachexia, medications, and assay variability. Available clinical data remain limited and are largely derived from small studies or case-based evidence. Conclusions: PRL should not currently be considered a standalone diagnostic, predictive, or treatment-selective biomarker in NSCLC. Its most realistic potential role is as a supplementary circulating marker within multimarker prognostic and monitoring models. Prospective validation with standardized sampling, assay procedures, and confounder adjustment is required before clinical implementation.<\/jats:p>","DOI":"10.3390\/jpm16070342","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T03:20:21Z","timestamp":1782357621000},"page":"342","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prolactin as a Candidate Biomarker in Non-Small Cell Lung Cancer: Implications for Personalized Medicine and Post-Treatment Risk Stratification"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5982-861X","authenticated-orcid":false,"given":"Filip","family":"Gajewski","sequence":"first","affiliation":[{"name":"Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Doktora Kazimierza Jaczewskiego 8, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7156-5812","authenticated-orcid":false,"given":"Grzegorz","family":"Kurec","sequence":"additional","affiliation":[{"name":"Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Doktora Kazimierza Jaczewskiego 8, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8181-0487","authenticated-orcid":false,"given":"Aleksandra","family":"Litkowska","sequence":"additional","affiliation":[{"name":"Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Doktora Kazimierza Jaczewskiego 8, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5525-7338","authenticated-orcid":false,"given":"Joanna","family":"Pec","sequence":"additional","affiliation":[{"name":"Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Doktora Kazimierza Jaczewskiego 8, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3742-5696","authenticated-orcid":false,"given":"Jakub","family":"Kleinrok","sequence":"additional","affiliation":[{"name":"Chair and Department of Clinical Pathomorphology at Medical University of Lublin, Kazimierza Jaczewskiego 8b, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9616-0458","authenticated-orcid":false,"given":"Weronika","family":"Paj\u0105k","sequence":"additional","affiliation":[{"name":"Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Doktora Kazimierza Jaczewskiego 8, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliwia","family":"Burdan","sequence":"additional","affiliation":[{"name":"Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Doktora Kazimierza Jaczewskiego 8, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"Krawczyk","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Genetics, Medical University of Lublin, Doktora Kazimierza Jaczewskiego 8, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Korolczuk","sequence":"additional","affiliation":[{"name":"Chair and Department of Clinical Pathomorphology at Medical University of Lublin, Kazimierza Jaczewskiego 8b, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref_1","first-page":"e70043","article-title":"Cancer statistics, 2026","volume":"76","author":"Siegel","year":"2026","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1055\/a-2651-0612","article-title":"Emerging trends in global lung cancer burden","volume":"46","author":"Shong","year":"2025","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"LMT60","DOI":"10.2217\/lmt-2023-0003","article-title":"Survival and quality-of-life outcomes in early-stage NSCLC patients: A literature review of real-world evidence","volume":"12","author":"Jovanoski","year":"2023","journal-title":"Lung Cancer Manag."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"\u0160uti\u0107, M., Vuki\u0107, A., Barana\u0161i\u0107, J., F\u00f6rsti, A., D\u017eubur, F., Samar\u017eija, M., Jakopovi\u0107, M., Br\u010di\u0107, L., and Kne\u017eevi\u0107, J. (2021). Diagnostic, predictive, and prognostic biomarkers in non-small cell lung cancer (NSCLC) management. J. Pers. Med., 11.","DOI":"10.3390\/jpm11111102"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1177\/1535370217750088","article-title":"Biomarker definitions and their applications","volume":"243","author":"Califf","year":"2018","journal-title":"Exp. Biol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s40291-013-0077-9","article-title":"Prognostic and predictive biomarkers: Tools in personalized oncology","volume":"18","author":"Nalejska","year":"2014","journal-title":"Mol. Diagn. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.annonc.2022.12.009","article-title":"Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"34","author":"Hendriks","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"321","DOI":"10.5858\/arpa.2017-0388-CP","article-title":"Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors","volume":"142","author":"Lindeman","year":"2018","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_9","unstructured":"Sholl, L.M., Cooper, W.A., Kerr, K.M., Tan, D.S.W., Tsao, M.-S., and Yang, J.C.-H. (2023). IASLC Atlas of Molecular Testing for Targeted Therapy in Lung Cancer, International Association for the Study of Lung Cancer."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/j.annonc.2025.06.004","article-title":"Updated treatment recommendations for systemic treatment: From the ESMO non-oncogene-addicted metastatic NSCLC Living Guideline","volume":"36","author":"Hendriks","year":"2025","journal-title":"Ann. Oncol."},{"key":"ref_11","unstructured":"FDA-NIH Biomarker Working Group (2016). BEST (Biomarkers, EndpointS, and Other Tools) Resource, National Institutes of Health."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1016\/j.ejca.2008.03.006","article-title":"Prognostic versus predictive value of biomarkers in oncology","volume":"44","author":"Oldenhuis","year":"2008","journal-title":"Eur. J. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1159\/000074432","article-title":"Tumor markers (CEA, CA 125, CYFRA 21-1, SCC and NSE) in patients with non-small cell lung cancer as an aid in histological diagnosis and prognosis","volume":"24","author":"Molina","year":"2003","journal-title":"Tumor Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e11448","DOI":"10.7717\/peerj.11448","article-title":"EGFR mutation status yield from bronchoalveolar lavage in patients with primary pulmonary adenocarcinoma compared to a venous blood sample and tissue biopsy","volume":"9","author":"Yanev","year":"2021","journal-title":"PeerJ"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kalkanis, A., Papadopoulos, D., Testelmans, D., Kopitopoulou, A., Boeykens, E., and Wauters, E. (2022). Bronchoalveolar lavage fluid-isolated biomarkers for the diagnostic and prognostic assessment of lung cancer. Diagnostics, 12.","DOI":"10.3390\/diagnostics12122949"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2838","DOI":"10.1158\/0008-5472.CAN-22-0554","article-title":"Genomic profiling of bronchoalveolar lavage fluid in lung cancer","volume":"82","author":"Nair","year":"2022","journal-title":"Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3968","DOI":"10.1200\/JCO.2015.63.3651","article-title":"Biomarker: Predictive or Prognostic?","volume":"33","author":"Ballman","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.pathol.2023.11.006","article-title":"Prognostic and predictive biomarkers in non-small cell lung carcinoma","volume":"56","author":"Odintsov","year":"2024","journal-title":"Pathology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"80","DOI":"10.5301\/jbm.5000177","article-title":"Clinical evaluation and therapeutic monitoring value of serum tumor markers in lung cancer","volume":"31","author":"Wang","year":"2016","journal-title":"Int. J. Biol. Markers"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1038\/bjc.2017.45","article-title":"Carcinoembryonic antigen and cytokeratin-19 fragments for assessment of therapy response in non-small cell lung cancer: A systematic review and meta-analysis","volume":"116","author":"Holdenrieder","year":"2017","journal-title":"Br. J. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1758835920952994","DOI":"10.1177\/1758835920952994","article-title":"CEA and CYFRA 21-1 as prognostic biomarker and as a tool for treatment monitoring in advanced NSCLC treated with immune checkpoint inhibitors","volume":"12","author":"Abbati","year":"2020","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Stares, M., Brown, L.R., Abhi, D., and Phillips, I. (2024). Prognostic biomarkers of systemic inflammation in non-small cell lung cancer: A narrative review of challenges and opportunities. Cancers, 16.","DOI":"10.3390\/cancers16081508"},{"key":"ref_23","first-page":"3","article-title":"Prolactin biology and laboratory measurement: An update on physiology and current analytical issues","volume":"39","author":"Saleem","year":"2018","journal-title":"Clin. Biochem. Rev."},{"key":"ref_24","unstructured":"Sadiq, N.M., and Tadi, P. (2023, May 01). Physiology, Pituitary Hormones, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK557556\/."},{"key":"ref_25","unstructured":"Thapa, S., and Bhusal, K. (2025, November 30). Hyperprolactinemia, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK537331\/."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"106403","DOI":"10.1016\/j.neubiorev.2025.106403","article-title":"Concerning the circadian rhythms of prolactin, its secretion timing, and regulation of the affiliative mind","volume":"179","author":"Mendoza","year":"2025","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_27","unstructured":"Al-Chalabi, M., Bass, A.N., and Alsalman, I. (2025, November 30). Physiology, Prolactin, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK507829\/."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Qi-Lytle, X., Sayers, S., and Wagner, E.J. (2023). Current review of the function and regulation of tuberoinfundibular dopamine neurons. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25010110"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Faron-G\u00f3recka, A., Latocha, K., Pabian, P., Kolasa, M., Sobczyk-Krupiarz, I., Dziedzicka-Wasylewska, M., and Ma\u0107kowiak, M. (2023). The involvement of prolactin in stress-related disorders. Int. J. Environ. Res. Public Health, 20.","DOI":"10.3390\/ijerph20043257"},{"key":"ref_30","unstructured":"Kolnikaj, T.S., Musat, M., Salehidoost, R., and Korbonits, M. (2025, November 30). Pharmacological Causes of Hyperprolactinemia, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK599196\/."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/s41574-023-00886-5","article-title":"Diagnosis and management of prolactin-secreting pituitary adenomas: A Pituitary Society international consensus statement","volume":"19","author":"Petersenn","year":"2023","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_32","unstructured":"Monteiro, A.L.S., and Glezer, A. (2025, November 30). Hyperprolactinemia, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK278984\/."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1210\/me.2013-1349","article-title":"Minireview: Extrapituitary prolactin: An update on the distribution, regulation, and functions","volume":"28","author":"Marano","year":"2014","journal-title":"Mol. Endocrinol."},{"key":"ref_34","unstructured":"Kamel-ElSayed, S.A., and Schwartz, J. (2023, May 01). Physiology, Pituitary Gland, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK459247\/."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"111084","DOI":"10.1016\/j.mce.2020.111084","article-title":"Three lactation-related hormones: Regulation of hypothalamus-pituitary axis and function on lactation","volume":"520","author":"Ni","year":"2021","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_36","unstructured":"Borba, V.V., and Bonf\u00e1, E. (2019). Prolactin as an inflammatory cytokine in systemic autoimmune diseases. Front. Immunol., 10."},{"key":"ref_37","first-page":"1007","article-title":"The effect of prolactin on immune cell subsets involved in SLE and other autoimmune diseases","volume":"42","year":"2022","journal-title":"Clin. Rheumatol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Pirchio, R., Graziadio, C., Colao, A., Pivonello, R., and Auriemma, R.S. (2022). Metabolic effects of prolactin. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1015520"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Macotela, Y., Ruiz-Herrera, X., V\u00e1zquez-Carrillo, D.I., Ram\u00edrez-Hernandez, G., Mart\u00ednez de la Escalera, G., and Clapp, C. (2022). The beneficial metabolic actions of prolactin. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1001703"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41389-020-00297-5","article-title":"Prolactin receptor-driven combined luminal and epithelial differentiation in breast cancer restricts plasticity, stemness, tumorigenesis and metastasis","volume":"10","author":"Shams","year":"2021","journal-title":"Oncogenesis"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Standing, D., Dandawate, P., and Anant, S. (2023). Prolactin receptor signaling: A novel target for cancer treatment\u2014Exploring anti-PRLR signaling strategies. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1112987"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1530\/EC-18-0116","article-title":"16 kDa vasoinhibin binds to integrin alpha5 beta1 on endothelial cells to induce apoptosis","volume":"7","author":"Morohoshi","year":"2018","journal-title":"Endocr. Connect."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1002\/ame2.12264","article-title":"The role of prolactin\/vasoinhibins in cardiovascular diseases","volume":"6","author":"Zhao","year":"2023","journal-title":"Anim. Model. Exp. Med."},{"key":"ref_44","first-page":"329","article-title":"Prolactin receptor isoforms as the basis of tissue-specific action of prolactin in the norm and pathology","volume":"84","author":"Abramicheva","year":"2019","journal-title":"Biochemistry"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Ferraris, J. (2023). Is prolactin receptor signaling a target in dopamine-resistant prolactinomas?. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1057749"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"bqae039","DOI":"10.1210\/endocr\/bqae039","article-title":"The human intermediate prolactin receptor I-tail contributes breast oncogenesis by targeting Ras\/MAPK pathway","volume":"165","author":"Shen","year":"2024","journal-title":"Endocrinology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"bqac122","DOI":"10.1210\/endocr\/bqac122","article-title":"Breast cancer and prolactin\u2014New mechanisms and models","volume":"163","author":"Clevenger","year":"2022","journal-title":"Endocrinol. Endocrinol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e13385","DOI":"10.1111\/jne.13385","article-title":"The prolactin receptor: A cross-species comparison of gene structure, transcriptional regulation, tissue-specificity, and genetic variation","volume":"36","author":"Banks","year":"2024","journal-title":"J. Neuroendocr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/s41523-021-00243-7","article-title":"The human intermediate prolactin receptor is a mammary proto-oncogene","volume":"7","author":"Grible","year":"2021","journal-title":"npj Breast Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"128604","DOI":"10.1016\/j.chemosphere.2020.128604","article-title":"Regulation of extracellular and intracellular prolactin on cell proliferation and survival rate through GHR\/JAK2\/STAT3 pathway in NSCLC","volume":"264","author":"Chou","year":"2021","journal-title":"Chemosphere"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"79572","DOI":"10.18632\/oncotarget.12840","article-title":"Stimulation of prolactin receptor induces STAT-5 phosphorylation and cellular invasion in glioblastoma multiforme","volume":"7","author":"Alkharusi","year":"2016","journal-title":"Oncotarget"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Biagetti, B., and Sim\u00f2, R. (2021). Molecular pathways in prolactinomas: Translational and therapeutic implications. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011247"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Lenke, L., Mart\u00ednez de la Escalera, G., Clapp, C., Bertsch, T., and Triebel, J. (2020). A Dysregulation of the Prolactin\/Vasoinhibin Axis Appears to Contribute to Preeclampsia. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00893"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"R1193","DOI":"10.1152\/ajpregu.00256.2015","article-title":"Principles of the prolactin\/vasoinhibin axis","volume":"309","author":"Triebel","year":"2015","journal-title":"Am. J. Physiol. Integr. Comp. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/978-3-319-12114-7_4","article-title":"Regulation of blood vessels by prolactin and vasoinhibins","volume":"846","author":"Clapp","year":"2015","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1111\/j.1582-4934.2011.01499.x","article-title":"Functional consequences of prolactin signalling in endothelial cells: A potential link with angiogenesis in pathophysiology?","volume":"16","author":"Reuwer","year":"2012","journal-title":"J. Cell. Mol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1210\/me.2012-1322","article-title":"PAK1 regulates breast cancer cell invasion through secretion of matrix metalloproteinases in response to prolactin and three-dimensional collagen IV","volume":"27","author":"Rider","year":"2013","journal-title":"Mol. Endocrinol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s12079-016-0373-3","article-title":"Inhibition of MT1-MMP proteolytic function and ERK1\/2 signalling influences cell migration and invasion through changes in MMP-2 and MMP-9 levels","volume":"11","author":"Cepeda","year":"2017","journal-title":"J. Cell Commun. Signal."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"da Silva, P.L., do Amaral, V.C., Gabrielli, V., Montt Guevara, M.M., Mannella, P., Baracat, E.C., Soares, J.M., and Simoncini, T. (2015). Prolactin promotes breast cancer cell migration through actin cytoskeleton remodeling. Front. Endocrinol., 6.","DOI":"10.3389\/fendo.2015.00186"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.semcdb.2020.10.005","article-title":"Prolactin: A hormone with diverse functions from mammary gland development to cancer metastasis","volume":"114","author":"Govindrajan","year":"2021","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.bbcan.2015.06.009","article-title":"Tissue-resident versus monocyte-derived macrophages in the tumor microenvironment","volume":"1865","author":"Lahmar","year":"2016","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_62","first-page":"85","article-title":"The prolactin receptor: Diverse and emerging roles in pathophysiology","volume":"2","author":"Gorvin","year":"2015","journal-title":"J. Clin. Transl. Endocrinol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.autrev.2014.11.005","article-title":"Prolactin: A versatile regulator of inflammation and autoimmune pathology","volume":"14","author":"Costanza","year":"2015","journal-title":"Autoimmun. Rev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"120277","DOI":"10.1016\/j.cca.2025.120277","article-title":"Prolactin as a novel biomarker in malignancy","volume":"572","author":"Safdari","year":"2025","journal-title":"Clin. Chim. Acta"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/s41571-025-01021-1","article-title":"Tumour and microenvironment crosstalk in NSCLC progression and response to therapy","volume":"22","author":"Rahal","year":"2025","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Wen, J., Yu, J.-Z., Liu, C., Ould Ismail, A.A.O., and Ma, W. (2024). Exploring the molecular tumor microenvironment and translational biomarkers in brain metastases of non-small-cell lung cancer. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042044"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Wang, J., Lan, H., Mao, X., and Chen, Y. (2024). Pituitary-adrenal axis dysfunction induced by tislelizumab immunotherapy for non-small cell lung cancer: A case series and literature review. BMC Pulm. Med., 24.","DOI":"10.1186\/s12890-024-03140-4"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Feng, Z., Fu, J., Wang, K., Yang, J., Jiang, X., and Wu, Q. (2025). Causal relationship between hormone levels and lung cancer: A Mendelian randomization study. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1462531"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"232","DOI":"10.5604\/01.3001.0013.1939","article-title":"The role of prolactin and its receptor in cancer development","volume":"73","year":"2019","journal-title":"Postep. Hig. Med. Dosw."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Schuler, L.A., and O\u2019Leary, K.A. (2022). Prolactin: The third hormone in breast cancer. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.910978"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Ciso\u0144-Jurek, S., Czajka-Francuz, P., Francuz, T., Owczarek, A.J., Szymczak, B., Wojnar, J., and Chudek, J. (2023). The value of prolactin, a panel of cytokines, and the soluble human epidermal growth factor receptor 2 in the prediction of rapid progression and shorter survival during palliative chemotherapy of colorectal cancer patients. Biomedicines, 11.","DOI":"10.3390\/biomedicines11072014"},{"key":"ref_72","first-page":"421","article-title":"The effects of novel and newly approved antipsychotics on serum prolactin levels: A comprehensive review","volume":"28","author":"Peuskens","year":"2014","journal-title":"CNS Drugs"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.2165\/00003495-200464200-00003","article-title":"Antipsychotic-induced hyperprolactinaemia","volume":"64","author":"Haddad","year":"2004","journal-title":"Drugs"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1210\/er.2009-0009","article-title":"The effects of opioids and opioid analogs on animal and human endocrine systems","volume":"31","author":"Vuong","year":"2010","journal-title":"Endocr. Rev."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/j.2040-4603.2016.tb00694.x","article-title":"Regulation of the hypothalamic-pituitary-adrenocortical stress response","volume":"6","author":"Herman","year":"2016","journal-title":"Compr. Physiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1159\/000464328","article-title":"Prolactin as a potential early predictive factor in metastatic non-small cell lung cancer patients treated with nivolumab","volume":"93","author":"Caponnetto","year":"2017","journal-title":"Oncology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1001\/jamaoncol.2017.3064","article-title":"Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: A systematic review and meta-analysis","volume":"4","author":"Barry","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1210\/edrv.19.3.0334","article-title":"Prolactin and its receptor: Actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice","volume":"19","author":"Goffin","year":"1998","journal-title":"Endocr. Rev."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s10238-025-01587-1","article-title":"Predictive value of serum cytokines in patients with non-small-cell lung cancer receiving anti-PD-1 blockade therapy: A meta-analysis","volume":"25","author":"Liu","year":"2025","journal-title":"Clin. Exp. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.lfs.2016.11.033","article-title":"TNF-\u03b1 and cancer cachexia: Molecular insights and clinical implications","volume":"170","author":"Patel","year":"2017","journal-title":"Life Sci."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Olson, B., Diba, P., Korzun, T., and Marks, D.L. (2021). Neural mechanisms of cancer cachexia. Cancers, 13.","DOI":"10.3390\/cancers13163990"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jare.2023.04.018","article-title":"Immunoregulation in cancer-associated cachexia","volume":"58","author":"Wu","year":"2024","journal-title":"J. Adv. Res."},{"key":"ref_83","first-page":"396","article-title":"The role of hypothalamic inflammation, the hypothalamic\u2013pituitary\u2013adrenal axis and serotonin in the cancer anorexia\u2013cachexia syndrome","volume":"20","author":"Dwarkasing","year":"2017","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"luad031","DOI":"10.1210\/jcemcr\/luad031","article-title":"Colon cancer presenting as pituitary mass and hypopituitarism: Recognition and multidisciplinary approach of a rare case","volume":"1","author":"Costanza","year":"2023","journal-title":"JCEM Case Rep."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1186\/s13256-021-03150-4","article-title":"Shrinkage of a pituitary metastasis of melanoma induced by pembrolizumab: A case report","volume":"15","author":"Giuffrida","year":"2021","journal-title":"J. Med. Case Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.endinu.2020.12.002","article-title":"Macroprolactin: From laboratory to clinical practice","volume":"69","author":"Biagetti","year":"2022","journal-title":"Endocrinol. Diabetes Y Nutr."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e70076","DOI":"10.1002\/prp2.70076","article-title":"From psychiatry to oncology: Exploring the anti-neoplastic mechanisms of aripiprazole and its potential use in cancer treatment","volume":"13","author":"Blum","year":"2025","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1007\/s11154-024-09886-w","article-title":"The relationship between low prolactin and type 2 diabetes","volume":"25","author":"Fluck","year":"2024","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Han, D., Zhao, K., Yang, Q., Zhang, L., and Fei, S. (2022). Secondary mutant ALK-I1171s in pituitary metastases from a patient with ALK fusion-positive advanced lung adenocarcinoma: A case report and literature review. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1016320"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Gupta, A., Kasaliwal, R., Das, L., Sharma, S.K., Kaur, V., Vasiljevic, A., Raverot, V., Korbonits, M., and Dutta, P. (2024). Ectopic acromegaly with tumoral range hyperprolactinemia and apoplexy with a dramatic regression of pituitary hyperplasia. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1473167"},{"key":"ref_91","first-page":"369","article-title":"Pituitary immune-related adverse events induced by programmed cell death protein 1 inhibitors in advanced lung cancer patients: A report of 3 cases","volume":"54","author":"Gu","year":"2022","journal-title":"Beijing Da Xue Xue Bao Yi Xue Ban"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1002\/ejp.1797","article-title":"Long-term opioid treatment and endocrine measures in chronic non-cancer pain patients: A systematic review and meta-analysis","volume":"25","author":"Diasso","year":"2021","journal-title":"Eur. J. Pain"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.12998\/wjcc.v12.i15.2597","article-title":"Pituitary metastasis from lung adenocarcinoma: A case report","volume":"12","author":"Wang","year":"2024","journal-title":"World J. Clin. Cases"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.3174\/ajnr.A8302","article-title":"Distinguishing pituitary metastasis and pituitary neuroendocrine tumors through conventional MR imaging and clinical features","volume":"45","author":"Yuzkan","year":"2024","journal-title":"Am. J. Neuroradiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"64","DOI":"10.5339\/qmj.2025.64","article-title":"Endocrine manifestations of lung adenocarcinoma with epidermal growth factor receptor mutation mimicking tuberculosis: A case report and literature review","volume":"2025","author":"Arafsha","year":"2025","journal-title":"Qatar Med. J."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Puglisi, M., May, L., Gardiyehewa, T., and Landry, J.W. (2025). Sex differences in the response to lung cancer and its relation to programmed cell death protein-1\/programmed death-ligand-1 checkpoint therapies. Cancers, 17.","DOI":"10.3390\/cancers17243953"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1038\/s41591-021-01450-2","article-title":"Toward personalized treatment approaches for non-small-cell lung cancer","volume":"27","author":"Wang","year":"2021","journal-title":"Nat. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3392","DOI":"10.21037\/tlcr-24-708","article-title":"A prognostic nomogram of non-small cell lung cancer based on tumor marker inflammatory nutrition score","volume":"13","author":"Feng","year":"2024","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s12967-019-1828-0","article-title":"The role of CEA, CYFRA21-1 and NSE in monitoring tumor response to Nivolumab in advanced non-small cell lung cancer patients","volume":"17","author":"Filiberti","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"17588359231206282","DOI":"10.1177\/17588359231206282","article-title":"Dynamic monitoring of serum tumor markers as prognostic factors in patients with advanced non-small-cell lung cancer treated with first-line immunotherapy: A multicenter retrospective study","volume":"15","author":"Yang","year":"2023","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Fang, R., Zhu, Y., Khadka, V.S., Zhang, F., Jiang, B., and Deng, Y. (2018). The evaluation of serum biomarkers for non-small cell lung cancer (NSCLC) diagnosis. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.01710"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1210\/jc.2010-1692","article-title":"Diagnosis and treatment of hyperprolactinemia: An Endocrine Society clinical practice guideline","volume":"96","author":"Melmed","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1159\/000499694","article-title":"Pitfalls in the diagnostic evaluation of hyperprolactinemia","volume":"109","author":"Vilar","year":"2019","journal-title":"Neuroendocrinology"},{"key":"ref_104","first-page":"1","article-title":"Prolactin in adipose tissue: Regulation and functions","volume":"846","author":"Hugo","year":"2015","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1081\/CBI-100101052","article-title":"Alterations with aging of the endocrine and neuroendocrine circadian system in humans","volume":"17","author":"Touitou","year":"2000","journal-title":"Chronobiol. Int. Chronobiol. Int."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/nrc3829","article-title":"Cancer cachexia: Understanding the molecular basis","volume":"14","author":"Busquets","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.4065\/80.8.1050","article-title":"Medication-Induced Hyperprolactinemia","volume":"80","author":"Molitch","year":"2005","journal-title":"Mayo Clin. Proc."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"E773","DOI":"10.1093\/neuros\/nyy386","article-title":"Prolactin-secreting lung adenocarcinoma metastatic to the pituitary mimicking a prolactinoma: A case report","volume":"85","author":"Yao","year":"2019","journal-title":"Neurosurgery"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1177\/0269881107087346","article-title":"Antipsychotics and hyperprolactinaemia: Clinical recommendations","volume":"22","author":"Peveler","year":"2008","journal-title":"J. Psychopharmacol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1177\/000456329703400305","article-title":"Macroprolactinaemia: Contribution to hyperprolactinaemia in a district general hospital and evaluation of a screening test based on precipitation with polyethylene glycol","volume":"34","author":"Soule","year":"1997","journal-title":"Ann. Clin. Biochem. Int."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Ioannidis, J.P.A. (2016). Why most clinical research is not useful. PLoS Med., 13.","DOI":"10.1371\/journal.pmed.1002049"}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/16\/7\/342\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T03:48:44Z","timestamp":1782359324000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/16\/7\/342"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,24]]},"references-count":111,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["jpm16070342"],"URL":"https:\/\/doi.org\/10.3390\/jpm16070342","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,24]]}}}