{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:09:15Z","timestamp":1760058555643,"version":"build-2065373602"},"reference-count":75,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Russian Science Foundation","award":["24-64-00028"],"award-info":[{"award-number":["24-64-00028"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Pancreatic cancer is a tumor with a poor prognosis, and improving its survival outcomes remains a formidable challenge, requiring a multidisciplinary approach that integrates innovative surgical and pharmacological strategies, guided by molecular and genetic insights. The pathomorphological and genetic characteristics of pancreatic cancer, reflected in morphological, immunohistochemical, and serological marker expression, reveal key patterns of tumor genotypic changes during carcinogenesis, aiding in prognostic evaluation and clinical strategy development. The mutational profile of pancreatic tumors is quite heterogeneous and diverse in terms of mutated genes, including in relation to morphological subtypes, but certain patterns have been identified as a result of studies. Pancreatic adenocarcinoma, for instance, is frequently driven by mutations regulating cell division (KRAS). The disease prognosis often depends on the morphological subtype and tumor microenvironment. Neuroendocrine tumors of the pancreas are characterized by a number of pathogenetic features that distinguish them from adenocarcinomas. Thus, neuroendocrine tumors are characterized by mutations of the MENIN protein, which prevents cells from entering the mitosis phase by stimulating the expression of cell cycle regulators. Thus, epithelial and neuroendocrine malignancies of the pancreas differ in immunohistochemical and genetic features, but there are similar mechanisms of pathogenesis, such as BRCA1 and BRCA2 gene mutations, impaired expression of p53 antioncogene, and HIF-2\u03b1 and mTOR receptor mutations. The predictive impact of serological markers, such as CA 19-9 and CEA, offers insights into tumor metastasis and long-term outcomes, emphasizing the need for personalized therapeutic strategies. Tailoring treatments based on individual molecular profiles holds promise for improving prognosis, as the genetic landscape of pancreatic tumors varies significantly between patients. This underscores the importance of a systematic, patient-specific approach that addresses tumor heterogeneity, resistance mechanisms, and the molecular underpinnings of carcinogenesis.<\/jats:p>","DOI":"10.3390\/life15040635","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T03:45:23Z","timestamp":1744343123000},"page":"635","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prognostic Impact of Phenotypic and Genetic Features of Pancreatic Malignancies"],"prefix":"10.3390","volume":"15","author":[{"given":"Mikhail B.","family":"Potievskiy","sequence":"first","affiliation":[{"name":"FSBI National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 249036 Obninsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lidia A.","family":"Nekrasova","sequence":"additional","affiliation":[{"name":"FSBI National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 249036 Obninsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan V.","family":"Korobov","sequence":"additional","affiliation":[{"name":"FSBI National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 249036 Obninsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8218-6774","authenticated-orcid":false,"given":"Ekaterina A.","family":"Bykova","sequence":"additional","affiliation":[{"name":"FSBI National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 249036 Obninsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruslan I.","family":"Moshurov","sequence":"additional","affiliation":[{"name":"FSBI National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 249036 Obninsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5050-7868","authenticated-orcid":false,"given":"Pavel V.","family":"Sokolov","sequence":"additional","affiliation":[{"name":"FSBI National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 249036 Obninsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter A.","family":"Shatalov","sequence":"additional","affiliation":[{"name":"FSBI National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 249036 Obninsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia A.","family":"Falaleeva","sequence":"additional","affiliation":[{"name":"FSBI National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 249036 Obninsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonid O.","family":"Petrov","sequence":"additional","affiliation":[{"name":"FSBI National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 249036 Obninsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir S.","family":"Trifanov","sequence":"additional","affiliation":[{"name":"FSBI National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 249036 Obninsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey A.","family":"Ivanov","sequence":"additional","affiliation":[{"name":"FSBI National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 249036 Obninsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter V.","family":"Shegai","sequence":"additional","affiliation":[{"name":"FSBI National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 249036 Obninsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrei D.","family":"Kaprin","sequence":"additional","affiliation":[{"name":"FSBI National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 249036 Obninsk, Russia"},{"name":"Department of Oncology and Radiology, Institute of Medicine, Peoples\u2019 Friendship University of Russia\u2014RUDN University, 6 Miklukho-Maklaya Street, 117198 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.pathol.2021.09.012","article-title":"The biology of pancreatic cancer morphology","volume":"54","author":"McDonald","year":"2022","journal-title":"Pathology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"471","DOI":"10.3322\/caac.21493","article-title":"Gastroenteropancreatic Neuroendocrine Tumors","volume":"68","author":"Cives","year":"2018","journal-title":"CA A Cancer J. Clin."},{"key":"ref_4","unstructured":"Kaprin, A.D., Starinsky, V.V., and Shakhzadova, A.O. (2022). The State of Cancer Care in Russia in 2021."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Yang, D.J., Xiong, J.J., Lu, H.M., Wei, Y., Zhang, L., Lu, S., and Hu, W.M. (2019). The oncological safety in minimally invasive versus open distal pancreatectomy for pancreatic ductal adenocarcinoma: A systematic review and meta-analysis. Sci. Rep., 9.","DOI":"10.1038\/s41598-018-37617-0"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1097\/SLA.0b013e31815b9cae","article-title":"Prognostic score predicting survival after resection of pancreatic neuroendocrine tumors: Analysis of 3851 patients","volume":"247","author":"Bilimoria","year":"2008","journal-title":"Ann. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. Clin."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1002\/bjs.6051","article-title":"Clinical outcome and long-term survival in 118 consecutive patients with neuroendocrine tumours of the pancreas","volume":"95","author":"Fischer","year":"2008","journal-title":"Br. J. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kaliszewski, K., Ludwig, M., Greniuk, M., Miku\u0142a, A., Zag\u00f3rski, K., and Rudnicki, J. (2022). Advances in the Diagnosis and Therapeutic Management of Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs). Cancers, 14.","DOI":"10.3390\/cancers14082028"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.asjsur.2022.05.117","article-title":"Pancreatic head cancer\u2014Current surgery techniques","volume":"46","author":"Olakowski","year":"2023","journal-title":"Asian J. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"216782","DOI":"10.1016\/j.canlet.2024.216782","article-title":"Conquering chemoresistance in pancreatic cancer: Exploring novel drug therapies and delivery approaches amidst desmoplasia and hypoxia","volume":"588","author":"Chintamaneni","year":"2024","journal-title":"Cancer Lett."},{"key":"ref_12","first-page":"17","article-title":"The role of adjuvant radiation therapy in pancreatic cancer\u2013within clinical studies","volume":"7","author":"Pokataev","year":"2017","journal-title":"Malig. Tumors"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.3748\/wjg.v26.i19.2305","article-title":"Pancreatic neuroendocrine tumors: A review of serum biomarkers, staging, and management","volume":"26","author":"Ma","year":"2020","journal-title":"World J. Gastroenterol."},{"key":"ref_14","first-page":"188367","article-title":"Molecular subtyping in pancreatic neuroendocrine neoplasms: New insights into clinical, pathological unmet needs and challenges. Biochimica et biophysica acta","volume":"1874","author":"Yan","year":"2020","journal-title":"Rev. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"610","DOI":"10.3109\/00365521.2015.1121515","article-title":"Comprehensive assessment of the prognosis of pancreatic cancer: Peripheral blood neutrophil-lymphocyte ratio and immunohistochemical analyses of the tumour site","volume":"51","author":"Takakura","year":"2016","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1053\/j.semdp.2021.10.003","article-title":"Immunohistochemistry as predictive and prognostic markers for gastrointestinal malignancies","volume":"39","author":"Rosenbaum","year":"2022","journal-title":"Semin. Diagn. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.humpath.2022.06.011","article-title":"Hepatoid tumors of the gastrointestinal\/pancreatobiliary district: Morphology, immunohistochemistry, and molecular profiles","volume":"132","author":"Mattiolo","year":"2023","journal-title":"Hum. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1007\/s00534-006-1166-5","article-title":"Molecular genetics of pancreatic intraepithelial neoplasia","volume":"14","author":"Feldmann","year":"2007","journal-title":"J. Hepato-Biliary-Pancreat. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4846","DOI":"10.3748\/wjg.v24.i43.4846","article-title":"Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes","volume":"24","author":"McGuigan","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8693","DOI":"10.3390\/curroncol29110686","article-title":"Pancreatic Tumorigenesis: Precursors, Genetic Risk Factors and Screening","volume":"29","author":"Badheeb","year":"2022","journal-title":"Curr. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4429","DOI":"10.1158\/1078-0432.CCR-17-0162","article-title":"Stratification of Pancreatic Ductal Adenocarcinoma: Combinatorial Genetic, Stromal, and Immunologic Markers","volume":"23","author":"Knudsen","year":"2017","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1080\/07853890.2018.1453168","article-title":"Pancreatic cancer subtypes: A roadmap for precision medicine","volume":"50","author":"Torres","year":"2018","journal-title":"Ann. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1001\/jamasurg.2018.1757","article-title":"Association of Immunologic Markers with Survival in Upfront Resectable Pancreatic Cancer","volume":"153","author":"Tang","year":"2018","journal-title":"JAMA Surg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1245\/s10434-017-6237-0","article-title":"T-Helper 1 Immune Response in Metastatic Lymph Nodes of Pancreatic Ductal Adenocarcinoma: A Marker for Prolonged Survival","volume":"25","author":"Nizri","year":"2018","journal-title":"Ann. Surg. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.immuni.2022.12.008","article-title":"Microenvironment-driven metabolic adaptations guiding CD8+ T cell anti-tumor immunity","volume":"56","author":"Jaeoh","year":"2023","journal-title":"Immunity"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e178","DOI":"10.1038\/s41424-018-0044-1","article-title":"A novel prognostic marker and immunogenic membrane antigen: Prohibitin (PHB) in pancreatic cancer","volume":"9","author":"Wang","year":"2018","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1186\/s40425-019-0703-0","article-title":"A PD-L2-based immune marker signature helps to predict survival in resected pancreatic ductal adenocarcinoma","volume":"7","author":"Zhang","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1038\/s41590-022-01224-z","article-title":"Epigenetic regulation of T cell exhaustion","volume":"23","author":"Belk","year":"2022","journal-title":"Nat. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1097\/PAS.0b013e318263209d","article-title":"Clinicopathologic study of 62 acinar cell carcinomas of the pancreas: Insights into the morphology and immunophenotype and search for prognostic markers","volume":"36","author":"Adsay","year":"2012","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/s41419-018-0661-3","article-title":"Significance of prohibitin domain family in tumorigenesis and its implication in cancer diagnosis and treatment","volume":"9","author":"Yang","year":"2018","journal-title":"Cell Death Disease"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/s41417-025-00883-y","article-title":"Emerging roles of prohibitins in cancer: An update","volume":"32","author":"Gao","year":"2025","journal-title":"Cancer Gene Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1002\/jhbp.210","article-title":"Molecular pathogenesis and targeted therapy of sporadic pancreatic neuroendocrine tumors","volume":"22","author":"Capurso","year":"2015","journal-title":"J. Hepato-Biliary-Pancreat. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Majer, A.D., Hua, X., and Katona, B.W. (2024). Menin in Cancer. Genes, 15.","DOI":"10.3390\/genes15091231"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1111\/1753-0407.13396","article-title":"The potential of \u03b2-cell growth promotion, continued","volume":"15","author":"Bloomgarden","year":"2023","journal-title":"J. Diabetes"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s12022-025-09848-1","article-title":"Clinical Relevance of ATRX\/DAXX Gene Mutations and ALT in Functioning Pancreatic Neuroendocrine Tumors","volume":"36","author":"Hackeng","year":"2025","journal-title":"Endocr. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1093\/annonc\/mds276","article-title":"Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): The NORDIC NEC study","volume":"24","author":"Sorbye","year":"2013","journal-title":"Ann. Oncol. Off. J. Eur. Soc. Med. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Stanciu, S., Ionita-Radu, F., Stefani, C., Miricescu, D., Stanescu-Spinu, I.I., Greabu, M., Ripszky Totan, A., and Jinga, M. (2022). Targeting PI3K\/AKT\/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical Aspects. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231710132"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Brunner, S.M., Weber, F., Werner, J.M., Agha, A., Farkas, S.A., Schlitt, H.J., and Hornung, M. (2015). Neuroendocrine tumors of the pancreas: A retrospective single-center analysis using the ENETS TNM-classification and immunohistochemical markers for risk stratification. BMC Surg., 15.","DOI":"10.1186\/s12893-015-0033-1"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1097\/01.sla.0000086659.49569.9e","article-title":"Aberrant hypermethylation of tumor suppressor genes in pancreatic endocrine neoplasms","volume":"238","author":"House","year":"2003","journal-title":"Ann. Surg."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Raj, N., Fazio, N., and Strosberg, J. (2018). Biology and Systemic Treatment of Advanced Gastroenteropancreatic Neuroendocrine Tumors, American Society of Clinical Oncology. Annual Meeting.","DOI":"10.1200\/EDBK_200893"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.cell.2012.03.017","article-title":"mTOR signaling in growth control and disease","volume":"149","author":"Laplante","year":"2012","journal-title":"Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1038\/bjc.2011.110","article-title":"Meta-analysis of immunohistochemical prognostic markers in resected pancreatic cancer","volume":"104","author":"Smith","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6661","DOI":"10.1158\/0008-5472.CAN-13-3742","article-title":"RABL6A promotes G1-S phase progression and pancreatic neuroendocrine tumor cell proliferation in an Rb1-dependent manner","volume":"74","author":"Hagen","year":"2014","journal-title":"Cancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6598","DOI":"10.1158\/1078-0432.CCR-04-0524","article-title":"Overexpression of G1-S cyclins and cyclin-dependent kinases during multistage human pancreatic duct cell carcinogenesis","volume":"10","author":"Radulovich","year":"2004","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"a026070","DOI":"10.1101\/cshperspect.a026070","article-title":"p53 in the DNA-Damage-Repair Process","volume":"6","author":"Williams","year":"2016","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1007\/s11864-011-0172-2","article-title":"Neuroendocrine pancreatic tumors: Guidelines for management and update","volume":"13","author":"Burns","year":"2012","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1533033820962117","DOI":"10.1177\/1533033820962117","article-title":"Pancreatic Cancer: A Review of Risk Factors, Diagnosis, and Treatment","volume":"19","author":"Zhao","year":"2020","journal-title":"Technol. Cancer Res. Treat."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/978-94-017-7215-0_15","article-title":"CA 19-9: Biochemical and Clinical Aspects","volume":"867","author":"Bottoni","year":"2015","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_49","first-page":"297","article-title":"Prognostic significance of CA19-9 levels in patients with pancreatic cancer","volume":"64","author":"Shiozawa","year":"2006","journal-title":"Nihon Rinsho"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"126","DOI":"10.3892\/mco.2022.2559","article-title":"Prognostic value of serum CEA and CA19-9 levels in pancreatic ductal adenocarcinoma","volume":"17","author":"Ermiah","year":"2022","journal-title":"Mol. Clin. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s00432-010-0965-x","article-title":"Serum biomarkers for improved diagnostic of pancreatic cancer: A current overview","volume":"137","author":"Laubert","year":"2011","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"S12","DOI":"10.1038\/nature24462","article-title":"Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer","volume":"551","author":"Balachandran","year":"2017","journal-title":"Nature"},{"key":"ref_53","first-page":"1002","article-title":"Prognostic value of carcinoembryonic antigen, alpha fetoprotein, carbohydrate antigen 125 and carbohydrate antigen 19-9 in gastroenteropancreatic neuroendocrine neoplasms","volume":"20","author":"Chen","year":"2017","journal-title":"Zhonghua Wei Chang Wai Ke Za Zhi"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1136\/gutjnl-2012-303434","article-title":"A genome wide association study of genetic loci that influence tumour biomarkers cancer antigen 19-9, carcinoembryonic antigen and \u03b1 fetoprotein and their associations with cancer risk","volume":"63","author":"He","year":"2014","journal-title":"Gut"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/nature10762","article-title":"Clonal evolution in cancer","volume":"481","author":"Greaves","year":"2012","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/nature19823","article-title":"A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns","volume":"538","author":"Notta","year":"2016","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1134\/S0022093022020028","article-title":"Prospects for the Application of Methods of Evolutionary Biology in Oncology","volume":"58","author":"Potievskii","year":"2022","journal-title":"J. Evol. Biochem. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"643","DOI":"10.3349\/ymj.2013.54.3.643","article-title":"Serum CA 19-9 and CEA levels as a prognostic factor in pancreatic adenocarcinoma","volume":"54","author":"Lee","year":"2013","journal-title":"Yonsei Med. J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/nrc.2016.66","article-title":"Pancreatic cancer biology and genetics from an evolutionary perspective","volume":"16","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s40164-020-00184-0","article-title":"Molecular drivers and cells of origin in pancreatic ductal adenocarcinoma and pancreatic neuroendocrine carcinoma","volume":"9","author":"Gao","year":"2020","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1245\/s10434-010-1006-3","article-title":"Chromogranin A--biological function and clinical utility in neuro endocrine tumor disease","volume":"17","author":"Modlin","year":"2010","journal-title":"Ann. Surg. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.hpb.2018.09.016","article-title":"Limited role of Chromogranin A as clinical biomarker for pancreatic neuroendocrine tumors","volume":"21","author":"Pulvirenti","year":"2019","journal-title":"HPB Off. J. Int. Hepato Pancreato Biliary Assoc."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1038\/ajg.2009.747","article-title":"Clinicopathological features of pancreatic endocrine tumors: A prospective multicenter study in Italy of 297 sporadic cases","volume":"105","author":"Zerbi","year":"2010","journal-title":"Am. J. Gastroenterol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"734","DOI":"10.3109\/00365521.2014.903432","article-title":"Survival and prognostic factors in well-differentiated pancreatic neuroendocrine tumors","volume":"49","author":"Vatn","year":"2014","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"E75","DOI":"10.1097\/MPA.0000000000002227","article-title":"Survival and Prognostic Factors in Patients with Pancreatic Colloid Carcinoma Compared with Pancreatic Ductal Adenocarcinoma","volume":"52","author":"Khalil","year":"2023","journal-title":"Pancreas"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1097\/MPA.0000000000001181","article-title":"The Levels of Tumor Markers in Pancreatic Neuroendocrine Carcinoma and Their Values in Differentiation Between Pancreatic Neuroendocrine Carcinoma and Pancreatic Ductal Adenocarcinoma","volume":"47","author":"Zhuge","year":"2018","journal-title":"Pancreas"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/s41588-019-0566-9","article-title":"Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution","volume":"52","author":"Kim","year":"2020","journal-title":"Nat. Genet."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/bjc.2017.209","article-title":"Clinical study of genomic drivers in pancreatic ductal adenocarcinoma","volume":"117","author":"Barrett","year":"2017","journal-title":"Br. J. Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/bjc.2017.398","article-title":"How the evolution of multicellularity set the stage for cancer","volume":"118","author":"Trigos","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s12943-018-0858-1","article-title":"Tumor microenvironment participates in metastasis of pancreatic cancer","volume":"17","author":"Ren","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.canlet.2021.06.027","article-title":"Advances in the epidemiology of pancreatic cancer: Trends, risk factors, screening, and prognosis","volume":"520","author":"Cai","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Zhou, X., Hu, K., Bailey, P., Springfeld, C., Roth, S., Kurilov, R., Brors, B., Gress, T., Buchholz, M., and An, J. (2021). Clinical Impact of Molecular Subtyping of Pancreatic Cancer. Front. Cell Dev. Biol., 9, Erratum in Front. Cell Dev. Biol. 2023, 11, 1179559.","DOI":"10.3389\/fcell.2023.1179559"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s10353-023-00814-x","article-title":"Personalized treatment in localized pancreatic cancer","volume":"56","author":"Neoptolemos","year":"2024","journal-title":"Eur. Surg."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e20240014","DOI":"10.1002\/INMD.20240014","article-title":"Red blood cell derived nanocarrier drug delivery system: A promising strategy for tumor therapy","volume":"2","author":"Wang","year":"2024","journal-title":"Interdiscip. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"9420025","DOI":"10.26599\/FMH.2024.9420025","article-title":"Research progress of microrobots in tumor drug delivery","volume":"1","author":"Wang","year":"2024","journal-title":"Food Med. Homol."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/4\/635\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:12:34Z","timestamp":1760029954000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/4\/635"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,11]]},"references-count":75,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["life15040635"],"URL":"https:\/\/doi.org\/10.3390\/life15040635","relation":{},"ISSN":["2075-1729"],"issn-type":[{"type":"electronic","value":"2075-1729"}],"subject":[],"published":{"date-parts":[[2025,4,11]]}}}