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

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.

A Systematic Review and Meta-analysis on the Occurrence of Biomarker Mutation in Colorectal Cancer among the Asian Population

“…The frequency of BRAF mutation varies globally, approximately 1.1–25% [ 16 , 49 , 135 – 139 ]. The prevalence of BRAF mutation obtained in this study was 5.6% (95% CI: 3.9-8.0), and this is conforming with the several existing findings, i.e., 1.1 to 5.8% in Asian studies and 5–21% in western studies [ 112 , 131 , 134 , 140 – 142 ]. Another reason for these prevalence similarities could be associated with genetic homogeneity as the studies involve certain regions, and their lifestyles and diet are almost similar [ 143 ].…”

“…BRAF is also a member of the RAF gene subfamily that, like KRAS, performs its function in the EGFR downstream cascade, but their mutations are less frequent than the KRAS gene mutations. Among the BRAF gene, BRAFV600E mutation is the most prevailing [ 134 ], and in this present study, BRAFV600E mutation is used to examine the prevalence of BRAF gene mutation in CRC. The frequency of BRAF mutation varies globally, approximately 1.1–25% [ 16 , 49 , 135 – 139 ].…”

Kolon Adenokarsinomlarında KRAS Mutasyon Durumunun Klinik Veriler ile Karşılaştırılması

“…In the study of Chang and colleagues, KRAS positivity ratio was determined as 47,56% and KRAS mutation ratio in welldifferentiated patients was found to be significantly higher than moderately differentiated patients (Chang et al, 2021). In a study conducted by Ikoma and colleagues from Japan, KRAS mutation ratio is determined as 48% (26% Codon 12, 17% Codon 13 and 5% non-Exon2 mutations) and while no correlation between KRAS mutation status with age and gender were found (Ikoma et al, 2021).…”

Вплив Клініко-Морфологічних Характеристик Пухлини На Віддалену Виживаність При Проксимальному Колоректальному Раку

“…Таким чином, виявлена нами у досить великій вибірці пацієнтів зміна виживання хворих могла бути пов'язана з нещодавно відкритими особливостями геномного ландшафту епітеліоцитів слизової товстої кишки. Або якимись іншими, досі невідомими причинами, що малоймовірно, враховуючи ті ж тенденції, виявлені до нас та іншими авторами [7,8]. Таким чином, на наш погляд, подальші дослідження та простежування змін біології та геноміки слизової товстої кишки при раку могло б пролити світло на виявлені нами закономірності.…”