{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:38:33Z","timestamp":1791315513976,"version":"4.3.1"},"reference-count":55,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T00:00:00Z","timestamp":1728259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003243","name":"Ministry of Health of the Czech Republic","doi-asserted-by":"publisher","award":["NT\/13638-4"],"award-info":[{"award-number":["NT\/13638-4"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Although the overall survival prognosis of patients in advanced stages of pancreatic ductal adenocarcinoma (PDAC) is poor, typically ranging from days to months from diagnosis, there are rare cases of patients remaining in therapy for longer periods of time. Early estimations of survival prognosis would allow rational decisions on complex therapy interventions, including radical surgery and robust systemic therapy regimens. Understandably, there is great interest in finding prognostic markers that can be used for patient stratification. We determined the role of various KRAS mutations in the prognosis of PDAC patients using biopsy samples and circulating tumor DNA. Methods: A total of 118 patients with PDAC, clinically confirmed by endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNB), were included in the study. DNA was extracted from cytological slides following a standard cytology evaluation to ensure adequacy (viability and quantity) and to mark the tumor cell fraction. Circulating tumor DNA (ctDNA) was extracted from plasma samples of 45 patients in stage IV of the disease. KRAS mutations in exons 12 and 13 were detected by denaturing capillary electrophoresis (DCE), revealing a minute presence of mutation-specific heteroduplexes. Kaplan\u2013Meier survival curves were calculated for individual KRAS mutation types. Results:KRAS mutations were detected in 90% of tissue (106\/118) and 44% of plasma (20\/45) samples. All mutations were localized at exon 2, codon 12, with G12D (GGT &gt; GAT) being the most frequent at 44% (47\/106) and 65% (13\/20), followed by other types including G12V (GGT &gt; GTT) at 31% (33\/106) and 10% (2\/20), G12R (GGT &gt; CGT) at 17% (18\/106) and 10% (2\/20), G12C (GGT\/TGT) at 5% (5\/106) and 0% (0\/20) and G12S (GGT\/AGT) at 1% (1\/106) and 5% (1\/20) in tissue and plasma samples, respectively. Two patients had two mutations simultaneously (G12V + G12S and G12D + G12S) in both types of samples (2%, 2\/106 and 10%, 2\/20 in tissue and plasma samples, respectively). The median survival of patients with the G12D mutation in tissues was less than half that of other patients (median survival 101 days, 95% CI: 80\u2013600 vs. 228 days, 95% CI: 184\u2013602), with a statistically significant overall difference in survival (p = 0.0080, log-rank test), and furthermore it was less than that of all combined patients with other mutation types (101 days, 95% CI: 80\u2013600 vs. 210 days, 95% CI: 161\u2013602, p = 0.0166). For plasma samples, the survival of patients with this mutation was six times shorter than that of patients without the G12D mutation (27 days, 95% CI: 8\u2013334 vs. 161 days, 95% CI: 107\u2013536, p = 0.0200). In contrast, patients with detected KRAS G12R in the tissue survived nearly twice as long as other patients in the aggregate (286 days, 95% CI: 70\u2013602 vs. 162 days, 95% CI: 122\u2013600, p = 0.0374) or patients with other KRAS mutations (286 days, 95% CI: 70\u2013602 vs. 137 days, 95% CI: 107\u2013600, p = 0.0257). Conclusions: Differentiation of specific KRAS mutations in EUS-FNB and ctDNA (above all, the crucial G12D and G12R) is feasible in routine management of PDAC patients and imperative for assessment of prognosis.<\/jats:p>","DOI":"10.3390\/genes15101302","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T06:23:18Z","timestamp":1728282198000},"page":"1302","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Prognostic Role of Specific KRAS Mutations Detected in Aspiration and Liquid Biopsies from Patients with Pancreatic Cancer"],"prefix":"10.3390","volume":"15","author":[{"given":"Tereza","family":"H\u00e1lkov\u00e1","sequence":"first","affiliation":[{"name":"Centre for Applied Genomics of Solid Tumors (CEGES), Genomac Research Institute, Drnovsk\u00e1 1112\/60, 161 00 Prague, Czech Republic"},{"name":"Department of Biochemistry, Faculty of Science, Charles University, Hlavova 8\/2030, 128 00 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bohu\u0161","family":"Bungani\u010d","sequence":"additional","affiliation":[{"name":"Department of Medicine, First Faculty of Medicine, Charles University and Military University Hospital, U Vojensk\u00e9 Nemocnice 1200, 169 02 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Traboulsi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Military University Hospital Prague, U Vojensk\u00e9 Nemocnice 1200, 169 02 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0615-6116","authenticated-orcid":false,"given":"Marek","family":"Min\u00e1rik","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Science, Charles University, Hlavova 8\/2030, 128 00 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miroslav","family":"Zavoral","sequence":"additional","affiliation":[{"name":"Department of Medicine, First Faculty of Medicine, Charles University and Military University Hospital, U Vojensk\u00e9 Nemocnice 1200, 169 02 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Bene\u0161ov\u00e1","sequence":"additional","affiliation":[{"name":"Centre for Applied Genomics of Solid Tumors (CEGES), Genomac Research Institute, Drnovsk\u00e1 1112\/60, 161 00 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4698","DOI":"10.3748\/wjg.v28.i32.4698","article-title":"International patterns in incidence and mortality trends of pancreatic cancer in the last three decades: A joinpoint regression analysis","volume":"28","author":"Ilic","year":"2022","journal-title":"World J. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1002\/jhbp.1359","article-title":"Early-onset pancreatic cancer: A national cancer registry study from the Czech Republic and review of the literature","volume":"30","author":"Whitley","year":"2023","journal-title":"J. Hepatobiliary Pancreat. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/j.1477-2574.2012.00571.x","article-title":"A contemporary analysis of survival for resected pancreatic ductal adenocarcinoma","volume":"15","author":"Lewis","year":"2013","journal-title":"HPB"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1053\/j.seminoncol.2021.02.003","article-title":"KRAS mutation in pancreatic cancer","volume":"48","author":"Luo","year":"2021","journal-title":"Semin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1634\/theoncologist.4-3-263","article-title":"The molecular perspective: The ras oncogene","volume":"4","author":"Goodsell","year":"1999","journal-title":"Oncologist"},{"key":"ref_6","first-page":"87","article-title":"Control of ras activation","volume":"27","author":"Downward","year":"1996","journal-title":"Cancer Surv."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/366643a0","article-title":"Proteins regulating Ras and its relatives","volume":"366","author":"Boguski","year":"1993","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1177\/1947601911408079","article-title":"RAS Interaction with PI3K, More Than Just Another Effector Pathway","volume":"2","author":"Castellano","year":"2011","journal-title":"Genes Cancer"},{"key":"ref_9","first-page":"115","article-title":"Mutant KRAS, chromosomal instability and prognosis in colorectal cancer","volume":"1756","author":"Castagnola","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3714","DOI":"10.3748\/wjg.v13.i27.3714","article-title":"Evaluation of clinical relevance of examining K-ras, p16 and p53 mutations along with allelic losses at 9p and 18q in EUS-guided fine needle aspiration samples of patients with chronic pancreatitis and pancreatic cancer","volume":"13","author":"Salek","year":"2007","journal-title":"World J. Gastroenterol."},{"key":"ref_11","first-page":"1803","article-title":"Mutation status of K-ras, p53 and allelic losses at 9p and 18q are not prognostic markers in patients with pancreatic cancer","volume":"29","author":"Salek","year":"2009","journal-title":"Anticancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s12253-018-0490-9","article-title":"Comparison of Native Aspirates and Cytological Smears Obtained by EUS-Guided Biopsies for Effective DNA\/RNA Marker Testing in Pancreatic Cancer","volume":"26","author":"Benesova","year":"2020","journal-title":"Pathol. Oncol. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1097\/MPA.0b013e31823cd9df","article-title":"Frequencies and prognostic role of KRAS and BRAF mutations in patients with localized pancreatic and ampullary adenocarcinomas","volume":"41","author":"Schultz","year":"2012","journal-title":"Pancreas"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Oldani, A., De Rosa, C., Monni, M., Terrone, A., Miglio, U., Garavoglia, M., and Boldorini, R. (2013). KRAS mutation analysis in ductal carcinoma of the pancreas; prognostic implications in elderly patients. BMC Surg., 13.","DOI":"10.1186\/1471-2482-13-S1-A31"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e157","DOI":"10.1038\/ctg.2016.18","article-title":"KRAS G12D Mutation Subtype Is A Prognostic Factor for Advanced Pancreatic Adenocarcinoma","volume":"7","author":"Bournet","year":"2016","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1038\/bjc.2017.115","article-title":"Extended RAS analysis and correlation with overall survival in advanced pancreatic cancer","volume":"116","author":"Haas","year":"2017","journal-title":"Br. J. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1111\/cas.16104","article-title":"Application of plasma circulating KRAS mutations as a predictive biomarker for targeted treatment of pancreatic cancer","volume":"115","author":"Lee","year":"2024","journal-title":"Cancer Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s12957-016-0888-3","article-title":"Prognostic significance of K-ras mutations in pancreatic cancer: A meta-analysis","volume":"14","author":"Tao","year":"2016","journal-title":"World J. Surg. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1093\/jnci\/djr523","article-title":"Effect of KRAS oncogene substitutions on protein behavior: Implications for signaling and clinical outcome","volume":"104","author":"Ihle","year":"2012","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.ccr.2013.01.023","article-title":"Selective requirement of PI3K\/PDK1 signaling for Kras oncogene-driven pancreatic cell plasticity and cancer","volume":"23","author":"Eser","year":"2013","journal-title":"Cancer Cell"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Dai, M., Jahanzaib, R., Liao, Y., Yao, F., Li, J., Teng, X., Chen, K., and Cheng, W. (2022). Prognostic value of KRAS subtype in patients with PDAC undergoing radical resection. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1074538"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41698-024-00505-0","article-title":"Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma","volume":"8","author":"Yousef","year":"2024","journal-title":"NPJ Precis. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.ab.2012.06.018","article-title":"Mutation-based detection and monitoring of cell-free tumor DNA in peripheral blood of cancer patients","volume":"433","author":"Benesova","year":"2013","journal-title":"Anal. Biochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"103109","DOI":"10.1016\/j.critrevonc.2020.103109","article-title":"ctDNA as a cancer biomarker: A broad overview","volume":"155","author":"Pessoa","year":"2020","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"103528","DOI":"10.1016\/j.critrevonc.2021.103528","article-title":"A systematic review and meta-analysis of the association between circulating tumor DNA (ctDNA) and prognosis in pancreatic cancer","volume":"168","author":"Guven","year":"2021","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"224ra24","DOI":"10.1126\/scitranslmed.3007094","article-title":"Detection of circulating tumor DNA in early- and late-stage human malignancies","volume":"6","author":"Bettegowda","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_27","unstructured":"(2024, August 19). COSMIC (Catalogue of Somatic Mutations in Cancer). Available online: http:\/\/cancer.sanger.ac.uk\/cosmic\/browse\/tissue."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2827","DOI":"10.3390\/cimb46040177","article-title":"Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer","volume":"46","author":"Stefanoudakis","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Nusrat, F., Khanna, A., Jain, A., Jiang, W., Lavu, H., Yeo, C.J., Bowne, W., and Nevler, A. (2024). The Clinical Implications of KRAS Mutations and Variant Allele Frequencies in Pancreatic Ductal Adenocarcinoma. J. Clin. Med., 13.","DOI":"10.3390\/jcm13072103"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1093\/jnci\/90.9.675","article-title":"Kirsten ras mutations in patients with colorectal cancer: The multicenter \u201cRASCAL\u201d study","volume":"90","author":"Andreyev","year":"1998","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/(SICI)1096-9896(199903)187:4<433::AID-PATH273>3.0.CO;2-E","article-title":"Structural differences between valine-12 and aspartate-12 Ras proteins may modify carcinoma aggression","volume":"187","author":"Going","year":"1999","journal-title":"J. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1001\/jama.2010.1535","article-title":"Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab","volume":"304","author":"Jonker","year":"2010","journal-title":"JAMA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/annonc\/mdq680","article-title":"Different types of K-Ras mutations could affect drug sensitivity and tumour behaviour in non-small-cell lung cancer","volume":"22","author":"Garassino","year":"2011","journal-title":"Ann. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3570","DOI":"10.1200\/JCO.2012.42.2592","article-title":"Association of KRAS G13D tumor mutations with outcome in patients with metastatic colorectal cancer treated with first-line chemotherapy with or without cetuximab","volume":"30","author":"Tejpar","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1038\/nrd4389","article-title":"Drugging the undruggable RAS: Mission possible?","volume":"13","author":"Cox","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1042\/BCJ20170441","article-title":"Progress in targeting RAS with small molecule drugs","volume":"476","author":"McCormick","year":"2019","journal-title":"Biochem. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1158\/2159-8290.CD-21-1331","article-title":"Expanding the Reach of Precision Oncology by Drugging All KRAS Mutants","volume":"12","author":"Hofmann","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1056\/NEJMoa1917239","article-title":"KRAS(G12C) Inhibition with Sotorasib in Advanced Solid Tumors","volume":"383","author":"Hong","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1056\/NEJMoa2103695","article-title":"Sotorasib for Lung Cancers with KRAS p.G12C Mutation","volume":"384","author":"Skoulidis","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4097","DOI":"10.1200\/JCO.23.00434","article-title":"Adagrasib in Advanced Solid Tumors Harboring a KRAS(G12C) Mutation","volume":"41","author":"Yaeger","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.cancergen.2012.12.003","article-title":"The dominant role of G12C over other KRAS mutation types in the negative prediction of efficacy of epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer","volume":"206","author":"Fiala","year":"2013","journal-title":"Cancer Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1007\/s10555-020-09903-9","article-title":"Current therapy of KRAS-mutant lung cancer","volume":"39","author":"Ghimessy","year":"2020","journal-title":"Cancer Metastasis Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3939","DOI":"10.1002\/cncr.33038","article-title":"Alterations in driver genes are predictive of survival in patients with resected pancreatic ductal adenocarcinoma","volume":"126","author":"McIntyre","year":"2020","journal-title":"Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Shen, H., Lundy, J., Strickland, A.H., Harris, M., Swan, M., Desmond, C., Jenkins, B.J., and Croagh, D. (2022). KRAS G12D Mutation Subtype in Pancreatic Ductal Adenocarcinoma: Does It Influence Prognosis or Stage of Disease at Presentation?. Cells, 11.","DOI":"10.3390\/cells11193175"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1093\/oncolo\/oyac179","article-title":"KRAS Mutation Variants and Co-occurring PI3K Pathway Alterations Impact Survival for Patients with Pancreatic Ductal Adenocarcinomas","volume":"27","author":"Diehl","year":"2022","journal-title":"Oncologist"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1007\/s00535-012-0664-2","article-title":"Prognostic value of K-ras mutation status and subtypes in endoscopic ultrasound-guided fine-needle aspiration specimens from patients with unresectable pancreatic cancer","volume":"48","author":"Ogura","year":"2013","journal-title":"J. Gastroenterol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Earl, J., Garcia-Nieto, S., Martinez-Avila, J.C., Montans, J., Sanjuanbenito, A., Rodr\u00edguez-Garrote, M., Lisa, E., Mend\u00eda, E., Lobo, E., and Malats, N. (2015). Circulating tumor cells (Ctc) and kras mutant circulating free DNA (cfdna)detection in peripheral blood as biomarkers in patients diagnosed with exocrine pancreatic cancer. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1779-7"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1002\/cncr.29364","article-title":"Detection of K-ras gene mutation by liquid biopsy in patients with pancreatic cancer","volume":"121","author":"Kinugasa","year":"2015","journal-title":"Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3109\/07357907.2014.1001894","article-title":"High levels of cell-free circulating nucleic acids in pancreatic cancer are associated with vascular encasement.; metastasis and poor survival","volume":"33","author":"Singh","year":"2015","journal-title":"Cancer Investig."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/bjc.2016.175","article-title":"Prognostic value of circulating tumour DNA in patients undergoing curative resection for pancreatic cancer","volume":"115","author":"Hadano","year":"2016","journal-title":"Br. J. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1002\/ijc.30650","article-title":"Analysis of ctDNA to predict prognosis and monitor treatment responses in metastatic pancreatic cancer patients","volume":"140","author":"Cheng","year":"2017","journal-title":"Int. J. Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1634\/theoncologist.2017-0467","article-title":"Mutant KRAS Circulating Tumor DNA Is an Accurate Tool for Pancreatic Cancer Monitoring","volume":"23","author":"Perets","year":"2018","journal-title":"Oncologist"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4973","DOI":"10.1158\/1078-0432.CCR-19-0197","article-title":"Circulating Tumor DNA as a Clinical Test in Resected Pancreatic Cancer","volume":"25","author":"Groot","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Watanabe, F., Suzuki, K., Tamaki, S., Abe, I., Endo, Y., Takayama, Y., Ishikawa, H., Kakizawa, N., Saito, M., and Futsuhara, K. (2019). Longitudinal monitoring of KRAS-mutated circulating tumor DNA enables the prediction of prognosis and therapeutic responses in patients with pancreatic cancer. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0227366"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/s41416-019-0704-2","article-title":"Preoperative detection of KRAS G12D mutation in ctDNA is a powerful predictor for early recurrence of resectable PDAC patients","volume":"122","author":"Guo","year":"2020","journal-title":"Br. J. Cancer"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/10\/1302\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:11:59Z","timestamp":1760112719000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/10\/1302"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,7]]},"references-count":55,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["genes15101302"],"URL":"https:\/\/doi.org\/10.3390\/genes15101302","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,7]]}}}