AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025120063
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ORIGINAL RESEARCH ARTICLE

Meta-analysis of the prognostic value of KRAS and TP53 mutations in cholangiocarcinoma

Benfeng Xu1 ,  Chuhan Zhang1 ,  Yibin Zhou1 ,  Jianan Jin1*
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1 Graduate School, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
EJMO, 025120063 https://doi.org/10.36922/EJMO025120063
Received: 22 March 2025 | Revised: 10 April 2025 | Accepted: 6 May 2025 | Published online: 22 May 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

KRAS and TP53 mutations are among the most common genetic mutations in cholangiocarcinoma. This study aimed to explore the potential impact of these mutations on the survival prognosis of cholangiocarcinoma patients through a meta-analysis. A systematic search was conducted in PubMed, Web of Science, Cochrane Library, Embase, CNKI, and Wanfang databases for cohort studies published up to April 2025 that investigated the relationship between KRAS and TP53 mutations and patient prognosis. Two researchers independently performed the literature screening and data extraction. Meta-analysis was conducted using RevMan 5.4 and Stata 17.0, with assessment of publication bias. Twelve studies were included, involving a total of 1,126 patients, with 167 cases of KRAS mutations and 176 cases of TP53 mutations. The results showed that both KRAS and TP53 mutations were significantly associated with poorer survival prognosis in cholangiocarcinoma patients. For KRAS (hazard ratio (HR)=7.26; 95% confidence interval (CI): 6.10 – 9.81; p<0.05) and TP53 (HR=18.13; 95% CI: 11.24 – 25.32; p<0.05), the presence of mutations predicted an adverse prognosis. While these findings suggest that KRAS and TP53 mutations are associated with worse survival in cholangiocarcinoma, the limited number and quality of the included studies warrant further high-quality research to validate these associations.

Keywords
Cholangiocarcinoma
KRAS mutation
TP53 mutation
Prognosis
Meta-analysis
Cohort studies
Funding
None.
Conflict of interest
The authors declare no conflicts of interest.
References
  1. Malaguarnera G, Giordano M, Paladina I, et al. Markers of bile duct tumors. World J Gastrointest Oncol. 2011;3(4):49-59. doi: 10.4251/wjgo.v3.i4.49

 

  1. Khan AS, Dageforde LA. Cholangiocarcinoma. Surg Clin North Am. 2019;99(2):315-335. doi: 10.1016/j.suc.2018.12.004

 

  1. Izquierdo-Sanchez L, Lamarca A, La Casta A, et al. Cholangiocarcinoma landscape in Europe: Diagnostic, prognostic and therapeutic insights from the ENSCCA registry. J Hepatol. 2022;76(5):1109-1121. doi: 10.1016/j.jhep.2021.12.010

 

  1. Cheng CY, Chen CP, Wu CE. Precision medicine in cholangiocarcinoma: Past, present, and future. Life (Basel). 2022;12(6):829. doi: 10.3390/life12060829

 

  1. Mateo-Victoriano B, Samaranayake GJ, Pokharel S, et al. Oncogenic KRAS addiction states differentially influence MTH1 expression and 8-oxodGTPase activity in lung adenocarcinoma. Redox Biol. 2025;82:103610. doi: 10.1016/j.redox.2025.103610

 

  1. Silva JL, De Andrade GC, Petronilho EC, et al. Phase separation and prion-like aggregation of p53 family tumor suppressors: From protein evolution to cancer treatment. J Neurochem. 2025;169(4):e70055. doi: 10.1111/jnc.70055

 

  1. Zhu XD, Amanjiaoer RH, Shen YL, et al. Combination of antiangiogenic and systemic therapy in advanced non-small cell lung cancer: Before and after progression to leptomeningeal metastasis. Sci Rep. 2025;15(1):11901. doi: 10.1038/s41598-025-91922-z

 

  1. Kale R, Samant C, Nandakumar K, Ranganath Pai KS, Bhonde M. Drugging the Undruggable and beyond: Emerging precision oncology approaches to target acquired resistance to KRAS G12C and KRAS G12D inhibitors. Biochem Biophys Res Commun. 2025;760:151688. doi: 10.1016/j.bbrc.2025.151688

 

  1. Zheng S, You Z, Guo G, Lin Z, Wang S, Yang G. Effect of KRAS mutation status on clinicopathological characteristics and overall survival in patients with rectal cancer. BMC Gastroenterol. 2025;25(1):37. doi: 10.1186/s12876-025-03615-6

 

  1. Zhao K, Karimi A, Kelly L, et al. TP53 mutation predicts worse survival and earlier local progression in patients with hepatocellular carcinoma treated with transarterial embolization. Current Oncol. 2025;32(1):51. doi: 10.3390/curroncol32010051

 

  1. Moffat GT, Hu ZI, Meric-Bernstam F, et al. KRAS allelic variants in biliary tract cancers. JAMA Netw Open. 2024;7(5):e249840. doi: 10.1001/jamanetworkopen.2024.9840

 

  1. Yu H, Xu Y, Gao W, et al. Comprehensive germline and somatic genomic profiles of Chinese patients with biliary tract cancer. Front Oncol. 2022;12:930611. doi: 10.3389/fonc.2022.930611

 

  1. Alaimo L, Boggio S, Catalano G, et al. Multi-omics classification of intrahepatic cholangiocarcinoma: A systematic review and meta-analysis. Cancers (Basel). 2024;16(14):2596. doi: 10.3390/cancers16142596

 

  1. Ellis H, Braconi C, Valle JW, Bardeesy N. Cholangiocarcinoma targeted therapies: Mechanisms of action and resistance. Am J Pathol. 2025;195(3):437-452. doi: 10.1016/j.ajpath.2024.11.005

 

  1. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603-605. doi: 10.1007/s10654-010-9491-z

 

  1. Hill MA, Alexander WB, Guo B, et al. Kras and Tp53 mutations cause cholangiocyte- and hepatocyte-derived cholangiocarcinoma. Cancer Res. 2018;78(16):4445-4451. doi: 10.1158/0008-5472.can-17-1123

 

  1. Huang L, Guo Z, Wang F, Fu L. KRAS mutation: From undruggable to druggable in cancer. Signal Transduct Target Ther. 2021;6(1):386. doi: 10.1038/s41392-021-00780-4

 

  1. Rivlin N, Brosh R, Oren M, Rotter V. Mutations in the p53 tumor suppressor gene: Important milestones at the various steps of tumorigenesis. Genes Cancer. 2011;2(4):466-474. doi: 10.1177/1947601911408889

 

  1. Ghidini M, Personeni N, Bozzarelli S, et al. KRAS mutation in lung metastases from colorectal cancer: Prognostic implications. Cancer Med. 2016;5(2):256-264. doi: 10.1002/cam4.592

 

  1. Robles AI, Harris CC. Clinical outcomes and correlates of TP53 mutations and cancer. Cold Spring Harb Perspect Biol. 2010;2(3):a001016. doi: 10.1101/cshperspect.a001016

 

  1. Formica V, Sera F, Cremolini C, et al. KRAS and BRAF mutations in stage II and III colon cancer: A systematic review and meta-analysis. J Natl Cancer Inst. 2022;114(4):517-527. doi: 10.1093/jnci/djab190

 

  1. Maddah MM, Hedayatizadeh-Omran A, Moosazadeh M, Alizadeh-Navaei R. Evaluation of the prognostic role of TP53 gene mutations in prostate cancer outcome: A systematic review and meta-analysis. Clin Genitourin Cancer. 2024;22(6):102226. doi: 10.1016/j.clgc.2024.102226

 

  1. Kealey J, Düssmann H, Llorente-Folch I, et al. Effect of TP53 deficiency and KRAS signaling on the bioenergetics of colon cancer cells in response to different substrates: A single cell study. Front Cell Dev Biol. 2022;10:893677. doi: 10.3389/fcell.2022.893677

 

  1. Yousef A, Yousef M, Chowdhury S, et al. Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma. NPJ Precis Oncol. 2024;8(1):27. doi: 10.1038/s41698-024-00505-0

 

  1. Peng J, Fang S, Li M, et al. Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis. Open Life Sci. 2023;18(1):20220652. doi: 10.1515/biol-2022-0652

 

  1. Chen F, Sheng J, Li X, et al. Unveiling the promise of PD1/PD-L1: A new dawn in immunotherapy for cholangiocarcinoma. Biomed Pharmacother. 2024;175:116659. doi: 10.1016/j.biopha.2024.116659

 

  1. Lei Z, Ma W, Si A, et al. Effect of different PD-1 inhibitor combination therapies for unresectable intrahepatic cholangiocarcinoma. Aliment Pharmacol Ther. 2023;58(6):611-622. doi: 10.1111/apt.17623

 

  1. Kim JY, Jung J, Kim KM, Lee J, Im YH. TP53 mutations predict poor response to immunotherapy in patients with metastatic solid tumors. Cancer Med. 2023;12(11):12438-12451. doi: 10.1002/cam4.5953

 

  1. Mugarza E, Van Maldegem F, Boumelha J, et al. Therapeutic KRASG12C inhibition drives effective interferon-mediated antitumor immunity in immunogenic lung cancers. Sci Adv. 2022;8(29):eabm8780. doi: 10.1126/sciadv.abm8780

 

  1. Skoulidis F, Goldberg ME, Greenawalt DM, et al. STK11/LKB1 mutations and PD-1 inhibitor resistance in KRAS-mutant lung adenocarcinoma. Cancer Discov. 2018;8(7):822-835. doi: 10.1158/2159-8290.cd-18-0099

 

  1. Dong ZY, Zhong WZ, Zhang XC, et al. Potential predictive value of TP53 and KRAS mutation status for response to PD-1 blockade immunotherapy in lung adenocarcinoma. Clin Cancer Res. 2017;23(12):3012-3024. doi: 10.1158/1078-0432.ccr-16-2554

 

  1. Gao G, Liao W, Ma Q, Zhang B, Chen Y, Wang Y. KRAS G12D mutation predicts lower TMB and drives immune suppression in lung adenocarcinoma. Lung Cancer. 2020;149:41-45. doi: 10.1016/j.lungcan.2020.09.004

 

  1. Budczies J, Romanovsky E, Kirchner M, et al. KRAS and TP53 co-mutation predicts benefit of immune checkpoint blockade in lung adenocarcinoma. Br J Cancer. 2024;131(3):524-533. doi: 10.1038/s41416-024-02746-z

 

  1. Frost N, Kollmeier J, Vollbrecht C, et al. KRASG12C/TP53 co-mutations identify long-term responders to first line palliative treatment with pembrolizumab monotherapy in PD-L1 high (≥50%) lung adenocarcinoma. Transl Lung Cancer Res. 2021;10(2):737-752. doi: 10.21037/tlcr-20-958

 

  1. Chen X, Wang D, Liu J, et al. Genomic alterations in biliary tract cancer predict prognosis and immunotherapy outcomes. J Immunother Cancer. 2021;9(11):e003214. doi: 10.1136/jitc-2021-003214

 

  1. Inamura K, Yokouchi Y, Kobayashi M, et al. Association of tumor TROP2 expression with prognosis varies among lung cancer subtypes. Oncotarget. 2017;8(17):28725-28735. doi: 10.18632/oncotarget.15647

 

  1. Putra J, De Abreu FB, Peterson JD, et al. Molecular profiling of intrahepatic and extrahepatic cholangiocarcinoma using next generation sequencing. Exp Mol Pathol. 2015;99(2):240-244. doi: 10.1016/j.yexmp.2015.07.005

 

  1. Tsilimigras DI, Stecko H, Moris D, Pawlik TM. Genomic profiling of biliary tract cancers: Comprehensive assessment of anatomic and geographic heterogeneity, co-alterations and outcomes. J Surg Oncol. 2025. doi: 10.1002/jso.28081

 

  1. Huang X, Du G, Yang Y, et al. Advancing bladder cancer management: Development of a prognostic model and personalized therapy. Front Immunol. 2024;15:1430792. doi: 10.3389/fimmu.2024.1430792

 

  1. Wang L, Li J, Mei N, et al. Identifying subtypes and developing prognostic models based on N6-methyladenosine and immune microenvironment related genes in breast cancer. Sci Rep. 2024;14(1):16586. doi: 10.1038/s41598-024-67477-w

 

  1. Khan SA, Tavolari S, Brandi G. Cholangiocarcinoma: Epidemiology and risk factors. Liver Int. 2019;39(Suppl 1):19-31. doi: 10.1111/liv.14095

 

  1. Khuntikeo N, Andrews RH, Petney TN, Khan SA. Introduction. Recent Results Cancer Res. 2023;219:1-5. doi: 10.1007/978-3-031-35166-2_1

 

  1. Tan S, Machrumnizar M. Fish and food-fatale: Food-borne trematode opisthorchis viverrini and cholangiocarcinoma. Helminthologia. 2023;60(4):287-299. doi: 10.2478/helm-2023-0036

 

  1. Boerner T, Drill E, Pak LM, et al. Genetic determinants of outcome in intrahepatic cholangiocarcinoma. Hepatology. 2021;74(3):1429-1444. doi: 10.1002/hep.31829

 

  1. Guo L, Zhou F, Liu H, et al. Genomic mutation characteristics and prognosis of biliary tract cancer. Am J Transl Res. 2022;14(7):4990-5002.

 

  1. Ardito F, Razionale F, Campisi A, et al. The impact of KRAS mutational status on long-term survival following liver resection for hilar cholangiocarcinoma. Cancers (Basel). 2022;14(18):4370. doi: 10.3390/cancers14184370

 

  1. Robertson S, Hyder O, Dodson R, et al. The frequency of KRAS and BRAF mutations in intrahepatic cholangiocarcinomas and their correlation with clinical outcome. Hum Pathol. 2013;44(12):2768-2773. doi: 10.1016/j.humpath.2013.07.026

 

  1. Javle M, Bekaii-Saab T, Jain A, et al. Biliary cancer: Utility of next-generation sequencing for clinical management. Cancer. 2016;122(24):3838-3847. doi: 10.1002/cncr.30254

 

  1. Jin B, Wang Y, Zhang B, et al. Immune checkpoint inhibitor-related molecular markers predict prognosis in extrahepatic cholangiocarcinoma. Cancer Med. 2023;12(20):20470-20481. doi: 10.1002/cam4.6441

 

  1. Ikeno Y, Seo S, Iwaisako K, et al. Preoperative metabolic tumor volume of intrahepatic cholangiocarcinoma measured by 18F-FDG-PET is associated with the KRAS mutation status and prognosis. J Transl Med. 2018;16(1):95. doi: 10.1186/s12967-018-1475-x

 

  1. Conci S, Ruzzenente A, Simbolo M, et al. Multigene mutational profiling of biliary tract cancer is related to the pattern of recurrence in surgically resected patients. Updates Surg. 2020;72(1):119-128. doi: 10.1007/s13304-020-00718-5

 

  1. Chao J, Wang S, Wang H, et al. Real-world cohort study of PD-1 blockade plus lenvatinib for advanced intrahepatic cholangiocarcinoma: Effectiveness, safety, and biomarker analysis. Cancer Immunol Immunother. 2023;72(11):3717-3726. doi: 10.1007/s00262-023-03523-2

 

  1. Chen TC, Jan YY, Yeh TS. K-ras mutation is strongly associated with perineural invasion and represents an independent prognostic factor of intrahepatic cholangiocarcinoma after hepatectomy. Ann Surg Oncol. 2012;19(Suppl 3):S675-S681. doi: 10.1245/s10434-012-2224-7

 

  1. Churi CR, Shroff R, Wang Y, et al. Mutation profiling in cholangiocarcinoma: Prognostic and therapeutic implications. PLoS One. 2014;9(12):e115383. doi: 10.1371/journal.pone.0115383
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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