Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 May 7;21(1):518.
doi: 10.1186/s12885-021-08271-z.

Clinical and prognostic features of patients with detailed RAS/BRAF-mutant colorectal cancer in Japan

Tatsuki Ikoma  1 , Mototsugu Shimokawa  2 , Masahito Kotaka  3 , Toshihiko Matsumoto  1 , Hiroki Nagai  1 , Shogen Boku  4 , Nobuhiro Shibata  4 , Hisateru Yasui  1 , Hironaga Satake  5
Affiliations

Clinical and prognostic features of patients with detailed RAS/BRAF-mutant colorectal cancer in Japan

Tatsuki Ikoma et al. BMC Cancer. .

Abstract

Background: RAS/BRAFV600E mutations are the most remarkable oncogenic driver mutations in colorectal cancer (CRC) and play an important role in treatment selection. No data are available regarding the clinical and prognostic features of patients with detailed RAS/BRAFV600E-mutant metastatic CRC (mCRC) in Japan.

Methods: A total of 152 chemotherapy-naïve patients with mCRC were included in this study between August 2018 and July 2019. Tumor samples were collected, and RAS/BRAFV600E status was investigated. RAS/BRAFV600E status was examined using a MEBGEN RASKET-B kit and polymerase chain reaction reverse sequence-specific oligonucleotide method.

Results: RAS/BRAFV600E mutations were detected in 54% of cases (KRAS codon 12, 26%; KRAS codon 13, 17%; KRAS non-Exon2, 5%; NRAS, 5%; and BRAFV600E, 7%). BRAFV600E-mutant CRC mainly existed in the right colon, whereas KRAS non-Exon2 and NRAS-mutant CRC was predominantly present in the left colon. KRAS non-Exon2 and NRAS-mutant CRC were associated with shorter survival time than RAS wild-type CRC (hazard ratio [HR], 2.26; 95% confidence interval [CI], 0.64-8.03; p = 0.19; HR, 2.42; 95% CI, 0.68-8.61; p = 0.16) and significantly shorter overall survival than KRAS Exon2-mutant CRC (HR, 3.88; 95% CI, 0.92-16.3; p = 0.04; HR, 4.80; 95% CI, 1.14-20.2; p = 0.02).

Conclusions: In our multicenter study, the findings elucidated the clinical and prognostic features of patients with detailed RAS/BRAFV600E-mutant mCRC in Japan.

Keywords: Colorectal cancer; KRAS Exon2; KRAS non-Exon2; NRAS.

PubMed Disclaimer

Conflict of interest statement

HS has received research funding from Ono Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and honoraria from Bayer, Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Eli Lilly Japan, Merck Bio Pharma, MSD, Ono Pharmaceutical, Sanofi, Taiho Pharmaceutical Co., Ltd., Takeda, and Yakult Honsha.

MK has received honoraria from Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Yakult, Taiho Pharma, and Merck Biopharma Co., Ltd.

The other physicians have no COI.

Figures

Fig. 1
Fig. 1
Frequencies of RAS/BRAFV600E mutation subtypes. N = 152 (KRAS Exon2 group: KRAS codon 12 and codon 13; KRAS non-Exon2 group: other KRAS mutations; wild group: no mutations)
Fig. 2
Fig. 2
Frequency of RAS/BRAFV600E mutations by primary tumor site (AC, ascending colon; TC, transverse colon; DC, descending colon; SC, sigmoid colon)
Fig. 3
Fig. 3
Overall survival (OS) of patients with different subtypes of RAS/BRAFV600E mutations. Analysis of hazard ratio of OS based on RAS/BRAFV600E mutation status in patients with colorectal cancer using Cox regression analysis (N = 152). P-value: Log-rank analysis
Fig. 4
Fig. 4
Overall survival (OS) of patients treated with doublet therapy with anti-vascular endothelial growth factor (anti-VEGF) agents. Analysis of hazard ratio of OS based on RAS mutation status in patients with colorectal cancer using Cox regression analysis (N = 43). P-value: Log-rank analysis
Fig. 5
Fig. 5
Progression-free survival (PFS) of patients treated with doublet therapy with anti-VEGF agents. Analysis of PFS of hazard ratio based on RAS mutation status in patients with colorectal cancer treated with doublet therapy with anti-VEGF agents using Cox regression analysis (N = 43). P-value: Log-rank analysis
See this image and copyright information in PMC

References

    1. Lièvre A, Bachet JB, Le Corre D, Boige V, Landi B, Emile J-F, et al. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res. 2006;66(8):3992–3995. doi: 10.1158/0008-5472.CAN-06-0191. - DOI - PubMed
    1. Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Williams R, Rong A, Wiezorek J, Sidhu R, Patterson SD. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. New Engl J Med. 2013;369(11):1023–1034. doi: 10.1056/NEJMoa1305275. - DOI - PubMed
    1. Schirripa M, Cohen SA, Battaglin F, Lenz H-J. Biomarker-driven and molecular targeted therapies for colorectal cancers. Semin Oncol. 2018;45(3):124–132. doi: 10.1053/j.seminoncol.2017.06.003. - DOI - PMC - PubMed
    1. Jonker DJ, O’Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au H-J, et al. Cetuximab for the treatment of colorectal cancer. New Engl J Med. 2007;357(20):2040–2048. doi: 10.1056/NEJMoa071834. - DOI - PubMed
    1. Karapetis CS, Khambata-Ford S, Jonker DJ, O’Callaghan CJ, Tu D, Tebbutt NC, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. New Engl J Med. 2008;359(17):1757–1765. doi: 10.1056/NEJMoa0804385. - DOI - PubMed