{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T10:02:29Z","timestamp":1784628149317,"version":"3.55.0"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>Background\/Objectives: Lung cancer tumors are the most frequent malignant tumors and the primary cause of cancer-related deaths. Despite the improvement in survival related to the implementation of immunotherapy, a significant proportion of patients fail to demonstrate satisfactory response. As a result, the need for new biomarkers, which will predict patient response, as well as for novel therapeutic targets, is urgent. SHP-2 is an intracellular signal transduction molecule, modifying signal transduction of numerous intracellular cascades, acting primarily as an oncogene. In this study we analyzed the expression pattern of SHP-2 in a cohort of non-small-cell lung cancer cases and attempted to correlate it with available clinicopathological parameters. Methods: We performed immunohistochemistry for SHP-2 detection in a cohort of 258 NSCLC cases. H-score was estimated and statistical analyses correlated it with survival and other clinicopathological and molecular parameters. Results: SHP-2 expression was observed in 60 cases (23.3%), with an H-score ranging from 150 to 300. Positive samples were distributed among the three major histological subtypes, without statistically significant differences. Statistical analysis revealed significant positive correlation of SHP-2 expression with smoking, PD-L1 levels, and KRAS mutations. Moreover, positive SHP-2 immunohistochemistry was associated with better clinical outcome in both the total cohort and in the group of patients who received immunotherapy. Finally, the simultaneous presence of SHP-2 expression and KRAS mutation was correlated with prolonged survival. Conclusions: Our findings indicate that SHP-2 could be a useful prognostic factor and a very reliable biomarker in predicting response to immune checkpoint inhibitors.<\/jats:p>","DOI":"10.3390\/pathophysiology33030052","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T07:54:13Z","timestamp":1784534053000},"page":"52","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SHP-2 Expression Is a Positive Prognostic Biomarker in Non-Small-Cell Lung Carcinoma: Association with KRAS Mutation and Prolonged Survival"],"prefix":"10.3390","volume":"33","author":[{"given":"Konstantinos","family":"Stamopoulos","sequence":"first","affiliation":[{"name":"Second Department of Internal Medicine, General and Oncology Hospital of Kifissia \u201cAgioi Anargyroi\u201d, Kifissia, 13561 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Pilichos","sequence":"additional","affiliation":[{"name":"Thoracic Surgery Department, Sotiria General Hospital for Chest Diseases, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Karatrasoglou","sequence":"additional","affiliation":[{"name":"First Department of Pathology, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1883-3898","authenticated-orcid":false,"given":"Penelope","family":"Korkolopoulou","sequence":"additional","affiliation":[{"name":"First Department of Pathology, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3639-6807","authenticated-orcid":false,"given":"Stratigoula","family":"Sakellariou","sequence":"additional","affiliation":[{"name":"First Department of Pathology, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Smolarz, B., \u0141ukasiewicz, H., Samulak, D., Piekarska, E., Ko\u0142aci\u0144ski, R., and Romanowicz, H. (2025). Lung Cancer\u2014Epidemiology, Pathogenesis, Treatment and Molecular Aspect (Review of Literature). Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26052049"},{"key":"ref_2","first-page":"45","article-title":"Epidemiology of Lung Cancer","volume":"25","author":"Thandra","year":"2021","journal-title":"Contemp. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"29S","DOI":"10.1378\/chest.07-1347","article-title":"Epidemiology of Lung Cancer: ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)","volume":"132","author":"Alberg","year":"2007","journal-title":"Chest"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.mpdhp.2025.11.004","article-title":"Pathology of Lung Tumours: WHO 2021 Updates and Resection Status","volume":"32","author":"Burke","year":"2026","journal-title":"Diagn. Histopathol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ro\u0219u, S.M., Biciu\u0219c\u0103, V., Stan, S.I., Mitroi, D.M., Mahler, B., Tra\u0219c\u0103, D.M., Popescu, M., P\u0103dureanu, M.M., Stoica, A.\u0218., and Pencea, T.I. (2026). Non-Small-Cell Lung Cancer: From Histopathological Classification to Precision Oncology\u2014A Narrative Review. J. Clin. Med., 15.","DOI":"10.3390\/jcm15083042"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.jtho.2021.11.003","article-title":"The 2021 WHO Classification of Lung Tumors: Impact of Advances Since 2015","volume":"17","author":"Nicholson","year":"2022","journal-title":"J. Thorac. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"578","DOI":"10.18632\/oncotarget.27905","article-title":"Molecular Characterization of Lung Squamous Cell Carcinoma Tumors Reveals Therapeutically Relevant Alterations","volume":"12","author":"Joshi","year":"2021","journal-title":"Oncotarget"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1038\/s42003-021-02470-x","article-title":"Mapping Lung Squamous Cell Carcinoma Pathogenesis through In Vitro and In Vivo Models","volume":"4","author":"Whiteman","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Seguin, L., Durandy, M., and Feral, C.C. (2022). Lung Adenocarcinoma Tumor Origin: A Guide for Personalized Medicine. Cancers, 14.","DOI":"10.3390\/cancers14071759"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1002\/ijc.34523","article-title":"Molecular Characteristics of Lung Adenocarcinoma with Respect to Patient Age at Diagnosis","volume":"153","author":"Staaf","year":"2023","journal-title":"Int. J. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e342","DOI":"10.1016\/S1470-2045(15)00077-7","article-title":"Genomic Alterations in Lung Adenocarcinoma","volume":"16","author":"Devarakonda","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"34014","DOI":"10.18632\/oncotarget.5607","article-title":"KRAS Mutations Affect Prognosis of Non-Small-Cell Lung Cancer Patients Treated with First-Line Platinum Containing Chemotherapy","volume":"6","author":"Marabese","year":"2015","journal-title":"Oncotarget"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3011","DOI":"10.1111\/1759-7714.14170","article-title":"Clinicopathological and Prognostic Implications of ALK Rearrangement in Patients with Completely Surgically Resected Lung Adenocarcinoma","volume":"12","author":"Zhang","year":"2021","journal-title":"Thorac. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nrc3239","article-title":"The Blockade of Immune Checkpoints in Cancer Immunotherapy","volume":"12","author":"Pardoll","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s12032-025-02822-1","article-title":"Immune Checkpoint Inhibitors in Cancer Therapy: What Lies beyond Monoclonal Antibodies?","volume":"42","author":"Zamani","year":"2025","journal-title":"Med. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Mamdani, H., Matosevic, S., Khalid, A.B., Durm, G., and Jalal, S.I. (2022). Immunotherapy in Lung Cancer: Current Landscape and Future Directions. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.823618"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3495","DOI":"10.3390\/curroncol31060258","article-title":"A Review of Immunotherapy in Non-Small-Cell Lung Cancer","volume":"31","author":"Capella","year":"2024","journal-title":"Curr. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"186","DOI":"10.3390\/immuno4030013","article-title":"Immune Checkpoint Inhibitors: Fundamental Mechanisms, Current Status and Future Directions","volume":"4","author":"Younis","year":"2024","journal-title":"Immuno"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1186\/s40425-019-0768-9","article-title":"The Role of PD-L1 Expression as a Predictive Biomarker: An Analysis of All US Food and Drug Administration (FDA) Approvals of Immune Checkpoint Inhibitors","volume":"7","author":"Davis","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1158\/1535-7163.MCT-14-0983","article-title":"PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy","volume":"14","author":"Patel","year":"2015","journal-title":"Mol. Cancer Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/s41392-023-01522-4","article-title":"Immune Checkpoint Therapy for Solid Tumours: Clinical Dilemmas and Future Trends","volume":"8","author":"Sun","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Meng, G., Liu, X., Ma, T., Lv, D., and Sun, G. (2022). Predictive Value of Tumor Mutational Burden for Immunotherapy in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0263629"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jtho.2023.08.009","article-title":"Targeting SHP2 Signaling in Lung Cancer","volume":"19","author":"Imbody","year":"2024","journal-title":"J. Thorac. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/s42003-021-01969-7","article-title":"Grb2 Binding Induces Phosphorylation-Independent Activation of Shp2","volume":"4","author":"Lin","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3259","DOI":"10.1038\/s41467-018-05768-3","article-title":"The Tyrosine Phosphatase SHP2 Controls TGF\u03b2-Induced STAT3 Signaling to Regulate Fibroblast Activation and Fibrosis","volume":"9","author":"Zehender","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1038\/s41591-018-0024-8","article-title":"Mutant KRAS-Driven Cancers Depend on PTPN11\/SHP2 Phosphatase","volume":"24","author":"Ruess","year":"2018","journal-title":"Nat. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1158\/1078-0432.CCR-19-3523","article-title":"Vertical Pathway Inhibition Overcomes Adaptive Feedback Resistance to KrasG12C Inhibition","volume":"26","author":"Ryan","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"L\u00f3pez Moreno, S.F., Lenz, S.A., Casso-Chapa, B., Paniagua-Bojorges, A., Kim, J.H., Palaskas, N.L., Nead, K.T., Samanthapudi, V.S.K., Mejia, G., and Hoang, O. (2025). SHP2: A Redox-Sensitive Regulator Linking Immune Checkpoint Inhibitor Therapy to Cancer Treatment and Vascular Risk. Antioxidants, 14.","DOI":"10.3390\/antiox14121388"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1158\/2326-6066.CIR-19-0744","article-title":"SHP-2 and PD-L1 Inhibition Combined with Radiotherapy Enhances Systemic Antitumor Effects in an Anti-PD-1-Resistant Model of Non-Small Cell Lung Cancer","volume":"8","author":"Chen","year":"2020","journal-title":"Cancer Immunol. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.febslet.2004.07.083","article-title":"PD-1 Inhibits T-Cell Receptor Induced Phosphorylation of the ZAP70\/CD3\u03b6 Signalosome and Downstream Signaling to PKC\u03b8","volume":"574","author":"Sheppard","year":"2004","journal-title":"FEBS Lett."},{"key":"ref_31","unstructured":"WHO Classification of Tumours Editorial Board (2021). Thoracic Tumours, International Agency for Research on Cancer. [5th ed.]."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s00428-020-02756-1","article-title":"Association between PD-L1 Expression and Driver Gene Mutations in Non-Small Cell Lung Cancer Patients: Correlation with Clinical Data","volume":"477","author":"Karatrasoglou","year":"2020","journal-title":"Virchows Arch."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e53","DOI":"10.5301\/jbm.5000165","article-title":"Comparative Expression Analysis of Putative Cancer Stem Cell Markers CD44 and ALDH1A1 in Various Skin Cancer Subtypes","volume":"31","author":"Erfani","year":"2016","journal-title":"Int. J. Biol. Markers"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.prp.2019.01.027","article-title":"Association of Nuclear Localization of SHP2 and YAP1 with Unfavorable Prognosis in Non-Small Cell Lung Cancer","volume":"215","author":"Chen","year":"2019","journal-title":"Pathol. Res. Pract."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1097\/PAI.0b013e31827da3f9","article-title":"Expression of SHP2 and Related Markers in Non-Small Cell Lung Cancer: A Tissue Microarray Study of 80 Cases","volume":"21","author":"Tang","year":"2013","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2411642","DOI":"10.1002\/advs.202411642","article-title":"Synthetic Lethality of SHP2 and XIAP Suppresses Proliferation and Metastasis in KRAS-Mutant Nonsmall Cell Lung Cancer","volume":"12","author":"Fu","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8816","DOI":"10.1158\/0008-5472.CAN-04-1923","article-title":"Activating Mutations of the Noonan Syndrome-Associated SHP2\/PTPN11 Gene in Human Solid Tumors and Adult Acute Myelogenous Leukemia","volume":"64","author":"Paez","year":"2004","journal-title":"Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1093\/carcin\/bgu025","article-title":"SHP2E76K Mutant Promotes Lung Tumorigenesis in Transgenic Mice","volume":"35","author":"Schneeberger","year":"2014","journal-title":"Carcinogenesis"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5465","DOI":"10.1080\/07391102.2024.2308771","article-title":"Discovery of 1H-Pyrazolo [3,4-b]Pyrazine Derivatives as Selective Allosteric Inhibitor of Protein Tyrosine Phosphatase SHP2 for the Treatment of KRASG12C-Mutant Non-Small Cell Lung Cancer","volume":"43","author":"Xu","year":"2025","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1038\/s41591-018-0023-9","article-title":"SHP2 Is Required for Growth of KRAS-Mutant Non-Small-Cell Lung Cancer in Vivo","volume":"24","author":"Mainardi","year":"2018","journal-title":"Nat. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1158\/1078-0432.CCR-20-2718","article-title":"Combinations with Allosteric SHP2 Inhibitor TNO155 to Block Receptor Tyrosine Kinase Signaling","volume":"27","author":"Liu","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.ejca.2021.10.003","article-title":"HER2 Mediates Clinical Resistance to the KRASG12C Inhibitor Sotorasib, Which Is Overcome by Co-Targeting SHP2","volume":"159","author":"Ho","year":"2021","journal-title":"Eur. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"36926","DOI":"10.1038\/s41598-025-20770-8","article-title":"Allosteric SHP2 Inhibitors Suppress Lung Cancer Cell Migration by Inhibiting Non-Canonical Activation of EphA2 via the ERK-RSK Signaling Pathway","volume":"15","author":"Nguyen","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e194377","DOI":"10.1172\/JCI194377","article-title":"EGFR Activation Disrupts Immunotherapy Response via SHP2-Mediated Suppression of Tumor-Intrinsic Response to IFN-\u03b3","volume":"136","author":"Zhuang","year":"2026","journal-title":"J. Clin. Investig."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2564","DOI":"10.1111\/1759-7714.14137","article-title":"High SHP2 Expression Determines the Efficacy of PD-1\/PD-L1 Inhibitors in Advanced KRAS Mutant Non-Small Cell Lung Cancer","volume":"12","author":"Feng","year":"2021","journal-title":"Thorac. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Chen, X., Keller, S.J., Hafner, P., Alrawashdeh, A.Y., Avery, T.Y., Norona, J., Zhou, J., and Ruess, D.A. (2024). Tyrosine Phosphatase PTPN11\/SHP2 in Solid Tumors-Bull\u2019s Eye for Targeted Therapy?. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1340726"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"16207","DOI":"10.1007\/s13277-015-4675-5","article-title":"Expression and Prognosis Value of SHP2 in Patients with Pancreatic Ductal Adenocarcinoma","volume":"37","author":"Zheng","year":"2016","journal-title":"Tumor Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1177\/030006051204000605","article-title":"Expression and Clinical Significance of SHP2 in Gastric Cancer","volume":"40","author":"Dong","year":"2012","journal-title":"J. Int. Med. Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Qi, C., Han, T., Tang, H., Huang, K., Min, J., Li, J., Ding, X., and Xu, Z. (2017). Shp2 Inhibits Proliferation of Esophageal Squamous Cell Cancer via Dephosphorylation of Stat3. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18010134"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"65676","DOI":"10.18632\/oncotarget.11601","article-title":"SHP-2 Phosphatase Contributes to KRAS-Driven Intestinal Oncogenesis but Prevents Colitis-Associated Cancer Development","volume":"7","author":"Coulombe","year":"2016","journal-title":"Oncotarget"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.humpath.2018.06.016","article-title":"Clinicopathological and Prognostic Significance of SHP2 and Hook1 Expression in Patients with Thyroid Carcinoma","volume":"81","author":"Cao","year":"2018","journal-title":"Hum. Pathol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.3892\/ol.2015.3479","article-title":"Expression and Clinical Significance of Tyrosine Phosphatase SHP2 in Thyroid Carcinoma","volume":"10","author":"Hu","year":"2015","journal-title":"Oncol. Lett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"20561","DOI":"10.1038\/s41598-021-99488-2","article-title":"Deregulation of Hsa_circ_0001971\/MiR-186 and Hsa_circ_0001874\/MiR-296 Signaling Pathways Promotes the Proliferation of Oral Squamous Carcinoma Cells by Synergistically Activating SHP2\/PLK1 Signals","volume":"11","author":"Wang","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1038\/onc.2015.184","article-title":"Shp2 Promotes Metastasis of Prostate Cancer by Attenuating the PAR3\/PAR6\/APKC Polarity Protein Complex and Enhancing Epithelial-to-Mesenchymal Transition","volume":"35","author":"Zhang","year":"2016","journal-title":"Oncogene"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1007\/s13277-012-0590-1","article-title":"Low Expression of SHP-2 Is Associated with Less Favorable Prostate Cancer Outcomes","volume":"34","author":"Tassidis","year":"2013","journal-title":"Tumour Biol."}],"container-title":["Pathophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1873-149X\/33\/3\/52\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T09:15:48Z","timestamp":1784625348000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1873-149X\/33\/3\/52"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,18]]},"references-count":55,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["pathophysiology33030052"],"URL":"https:\/\/doi.org\/10.3390\/pathophysiology33030052","relation":{},"ISSN":["1873-149X"],"issn-type":[{"value":"1873-149X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,18]]}}}