The BRAF Mutation is Associated with the Prognosis in Colorectal Cancer

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2014 Jun 20

PMID 24942334

Citations 14

Authors

Tae Sung Ahn

Dongjun Jeong

Myoung Won Son

Haeil Jung

Soyoung Park

Hyungjoo Kim

Sang Byung Bae

Han Jo Kim

Young-Woo Jeon

Moon Soo Lee

Moo-Jun Baek

Affiliations

Soon will be listed here.

Abstract

Background: Two members of the Ras/Raf signaling pathway, KRAS and B-raf, are suspected to be involved in the stepwise progression of colorectal cancer (CRC) tumorigenesis.

Objective: We compared the KRAS and BRAF mutation status of CRC patients with their clinicopathological characteristics and examined the effect of mutation status on survival rates.

Methods: DNA was extracted from 164 samples, and the mutation statuses of KRAS and BRAF were assessed using peptide PNA clamp real-time PCR method. The presences of mutation were compared with clinicopathological factors and 5-year survival rate.

Results: Among the 164 CRC cases, KRAS mutation as detected in 71 cases (43.3 %), respectively, with no relationship with clinicopathological factors of the patients. On Kaplan-Meier survival analysis, KRAS mutation was not significantly associated with survival (p = 0.971). BRAF mutation was detected in 26 cases (15.9 %) and not associated with clinicopathological factors of the patients. However, the 5-year survival rate of BRAF mutations was significantly decreased (p = 0.02).

Conclusions: The presence of KRAS mutation did not correlate with the various clinicopathological factors of CRC patients or the survival rate. However, the survival rate was reduced in BRAF-mutated CRC patients. Therefore, BRAF mutation could be an important prognostic factor in CRC patients.

Citing Articles

Antitumor Efficacy of Dual Blockade with Encorafenib + Cetuximab in Combination with Chemotherapy in Human BRAFV600E-Mutant Colorectal Cancer.

Napolitano S, Woods M, Lee H, De Falco V, Martini G, Della Corte C Clin Cancer Res. 2023; 29(12):2299-2309.

PMID: 37040395 PMC: 10261917. DOI: 10.1158/1078-0432.CCR-22-3894.

The Spectrum, Tendency and Predictive Value of Mutation in Chinese Colorectal Cancer Patients.

Fu X, Lin H, Fan X, Zhu Y, Wang C, Chen Z Front Oncol. 2021; 11:595675.

PMID: 33842311 PMC: 8032977. DOI: 10.3389/fonc.2021.595675.

Signal transduction pathway mutations in gastrointestinal (GI) cancers: a systematic review and meta-analysis.

Tabibzadeh A, Safarnezhad Tameshkel F, Moradi Y, Soltani S, Moradi-Lakeh M, Ashrafi G Sci Rep. 2020; 10(1):18713.

PMID: 33127962 PMC: 7599243. DOI: 10.1038/s41598-020-73770-1.

Gene Expression Signature to Predict Prognosis and Adjuvant Chemosensitivity of Colorectal Cancer Patients.

Li J, Zhang J, Hu H, Cai Y, Ling J, Wu Z Cancer Manag Res. 2020; 12:3301-3310.

PMID: 32494194 PMC: 7227814. DOI: 10.2147/CMAR.S243490.

High Frequency of KRAS Codon 146 and FBXW7 Mutations in Thai Patients with Stage II-III Colon Cancer.

Korphaisarn K, Pongpaibul A, Roothumnong E, Pongsuktavorn K, Thamlikitkul L, Anekpuritanang T Asian Pac J Cancer Prev. 2019; 20(8):2319-2326.

PMID: 31450901 PMC: 6852819. DOI: 10.31557/APJCP.2019.20.8.2319.

References

French A, Sargent D, Burgart L, Foster N, Kabat B, Goldberg R . Prognostic significance of defective mismatch repair and BRAF V600E in patients with colon cancer. Clin Cancer Res. 2008; 14(11):3408-15. PMC: 2674786. DOI: 10.1158/1078-0432.CCR-07-1489. View

Samowitz W, Sweeney C, Herrick J, Albertsen H, Levin T, Murtaugh M . Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers. Cancer Res. 2005; 65(14):6063-9. DOI: 10.1158/0008-5472.CAN-05-0404. View

Saridaki Z, Papadatos-Pastos D, Tzardi M, Mavroudis D, Bairaktari E, Arvanity H . BRAF mutations, microsatellite instability status and cyclin D1 expression predict metastatic colorectal patients' outcome. Br J Cancer. 2010; 102(12):1762-8. PMC: 2883698. DOI: 10.1038/sj.bjc.6605694. View

Ogino S, Nosho K, Kirkner G, Kawasaki T, Meyerhardt J, Loda M . CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer. Gut. 2008; 58(1):90-6. PMC: 2679586. DOI: 10.1136/gut.2008.155473. View

Jemal A, Bray F, Center M, Ferlay J, Ward E, Forman D . Global cancer statistics. CA Cancer J Clin. 2011; 61(2):69-90. DOI: 10.3322/caac.20107. View

Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F, Zanon C, Moroni M, Veronese S . Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res. 2007; 67(6):2643-8. DOI: 10.1158/0008-5472.CAN-06-4158. View

Van Cutsem E, Kohne C, Hitre E, Zaluski J, Chang Chien C, Makhson A . Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009; 360(14):1408-17. DOI: 10.1056/NEJMoa0805019. View

Nosho K, Irahara N, Shima K, Kure S, Kirkner G, Schernhammer E . Comprehensive biostatistical analysis of CpG island methylator phenotype in colorectal cancer using a large population-based sample. PLoS One. 2008; 3(11):e3698. PMC: 2579485. DOI: 10.1371/journal.pone.0003698. View

Andersen S, Lovig T, Breivik J, Lund E, Gaudernack G, Meling G . K-ras mutations and prognosis in large-bowel carcinomas. Scand J Gastroenterol. 1997; 32(1):62-9. DOI: 10.3109/00365529709025065. View

10.

Rajagopalan H, Bardelli A, Lengauer C, Kinzler K, Vogelstein B, Velculescu V . Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature. 2002; 418(6901):934. DOI: 10.1038/418934a. View

11.

Schubbert S, Shannon K, Bollag G . Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer. 2007; 7(4):295-308. DOI: 10.1038/nrc2109. View

12.

Popescu N, Amsbaugh S, DIPAOLO J, Tronick S, Aaronson S, Swan D . Chromosomal localization of three human ras genes by in situ molecular hybridization. Somat Cell Mol Genet. 1985; 11(2):149-55. DOI: 10.1007/BF01534703. View

13.

Sithanandam G, Kolch W, Duh F, Rapp U . Complete coding sequence of a human B-raf cDNA and detection of B-raf protein kinase with isozyme specific antibodies. Oncogene. 1990; 5(12):1775-80. View

14.

Ikenoue T, Hikiba Y, Kanai F, Tanaka Y, Imamura J, Imamura T . Functional analysis of mutations within the kinase activation segment of B-Raf in human colorectal tumors. Cancer Res. 2003; 63(23):8132-7. View

15.

Kranenburg O . The KRAS oncogene: past, present, and future. Biochim Biophys Acta. 2005; 1756(2):81-2. DOI: 10.1016/j.bbcan.2005.10.001. View

16.

Di Nicolantonio F, Martini M, Molinari F, Sartore-Bianchi A, Arena S, Saletti P . Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol. 2008; 26(35):5705-12. DOI: 10.1200/JCO.2008.18.0786. View

17.

Karapetis C, Khambata-Ford S, Jonker D, OCallaghan C, Tu D, Tebbutt N . K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008; 359(17):1757-65. DOI: 10.1056/NEJMoa0804385. View

18.

Gonzalez-Aguilera J, Oliart S, Moreno Azcoita M, Fernandez-Peralta A . Simultaneous mutations in K-ras and TP53 are indicative of poor prognosis in sporadic colorectal cancer. Am J Clin Oncol. 2004; 27(1):39-45. DOI: 10.1097/01.coc.0000045920.49210.7a. View

19.

Fransen K, Klintenas M, Osterstrom A, Dimberg J, Monstein H, Soderkvist P . Mutation analysis of the BRAF, ARAF and RAF-1 genes in human colorectal adenocarcinomas. Carcinogenesis. 2003; 25(4):527-33. DOI: 10.1093/carcin/bgh049. View

20.

Baselga J, Rosen N . Determinants of RASistance to anti-epidermal growth factor receptor agents. J Clin Oncol. 2008; 26(10):1582-4. DOI: 10.1200/JCO.2007.15.3700. View