Clinicopathological Features and Prognostic Value of KRAS/NRAS/BRAF Mutations in Colorectal Cancer Patients of Central China

Xiao-na Chang , Fu-mei Shang , Hong-yu Jiang , Chen Chen , Zhe-yan Zhao , Sheng-he Deng , Jun Fan , Xiao-chuan Dong , Ming Yang , Yan Li , Kai-lin Cai , Li Liu , Hong-li Liu , Xiu Nie

Current Medical Science ›› 2021, Vol. 41 ›› Issue (1) : 118 -126.

PDF
Current Medical Science ›› 2021, Vol. 41 ›› Issue (1) : 118 -126. DOI: 10.1007/s11596-021-2326-1
Article

Clinicopathological Features and Prognostic Value of KRAS/NRAS/BRAF Mutations in Colorectal Cancer Patients of Central China

Author information +
History +
PDF

Abstract

The incidence of colorectal cancer (CRC) is increasing in China, with high mortality. Here, we aimed to evaluate the latest clinicopathological features and prognostic value of the KRAS/NRAS/BRAF mutation status in CRC patients in Central China. The clinical data of 1549 CRC patients with stage I-IV disease diagnosed at Union Hospital, Tongji Medical College of Huazhong University of Science and Technology from 2015 to 2017 were collected and analyzed retrospectively. KRAS/NRAS/BRAF mutations were detected by real-time quantitative polymerase chain reaction (q-PCR) in 410 CRC patients, with mutation frequencies of KRAS, NRAS and BRAF of 47.56%, 2.93% and 4.15%, respectively. The gene mutation status and clinicopathological characteristics of 410 patients with CRC who underwent qPCR were analyzed. The KRAS and BRAF gene mutations were related to the pathological differentiation and number of metastatic lymph nodes. The BRAF gene mutation was also associated with cancer thrombosis in blood vessels. Cox regression analysis showed that there was no statistically significant difference in the overall survival (OS) between patients with KRAS, NRAS mutants and wild-type CRC patients, while the BRAF gene mutation was negatively correlated with the OS rate of CRC patients. It is suggested that the BRAF gene mutation may be an independent risk factor for the prognosis of CRC.

Keywords

colorectal cancer / KRAS mutation / NRAS mutation / BRAF mutation / prognosis

Cite this article

Download citation ▾
Xiao-na Chang, Fu-mei Shang, Hong-yu Jiang, Chen Chen, Zhe-yan Zhao, Sheng-he Deng, Jun Fan, Xiao-chuan Dong, Ming Yang, Yan Li, Kai-lin Cai, Li Liu, Hong-li Liu, Xiu Nie. Clinicopathological Features and Prognostic Value of KRAS/NRAS/BRAF Mutations in Colorectal Cancer Patients of Central China. Current Medical Science, 2021, 41(1): 118-126 DOI:10.1007/s11596-021-2326-1

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

SiegelRL, MillerKD, JemalA. Cancer Statistics, 2017. CA Cancer J Clin, 2017, 67(1): 7-30

[2]

SantosC, AzuaraD, VieitezJM, et al.. Phase II study of high-sensitivity genotyping of KRAS, NRAS, BRAF and PIK3CA to ultra-select metastatic colorectal cancer patients for panitumumab plus FOLFIRI: the ULTRA trial. Ann Oncol, 2019, 30(5): 796-803

[3]

MizukamiT, IzawaN, NakajimaTE, et al.. Targeting EGFR and RAS/RAF Signaling in the Treatment of Metastatic Colorectal Cancer: From Current Treatment Strategies to Future Perspectives. Drugs, 2019, 79(6): 633-645

[4]

TherkildsenC, BergmannTK, Henrichsen-SchnackT, et al.. The predictive value of KRAS, NRAS, BRAF, PIK3CA and PTEN for anti-EGFR treatment in metastatic colorectal cancer: A systematic review and meta-analysis. Acta Oncol, 2014, 53(7): 852-864

[5]

ZhangX, LiuG, DingL, et al.. HOXA3 promotes tumor growth of human colon cancer through activating EGFR/Ras/Raf/MEK/ERK signaling pathway. J Cell Biochem, 2018, 119(3): 2864-2874

[6]

WorthleyDL, WhitehallVL, SpringKJ, et al.. Colorectal carcinogenesis: road maps to cancer. World J Gastroenterol, 2007, 13(28): 3784-3791

[7]

VaughnCP, ZobellSD, FurtadoLV, et al.. Frequency of KRAS, BRAF, and NRAS mutations in colorectal cancer. Genes Chromosomes Cancer, 2011, 50(5): 307-312

[8]

RyanMB, CorcoranRB. Therapeutic strategies to target RAS-mutant cancers. Nat Rev Clin Oncol, 2018, 15(11): 709-720

[9]

DaviesH, BignellGR, CoxC, et al.. Mutations of the BRAF gene in human cancer. Nature, 2002, 417(6892): 949-954

[10]

DouillardJY, OlinerKS, SienaS, et al.. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med, 2013, 369(11): 1023-1034

[11]

RothAD, TejparS, DelorenziM, et al.. Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J Clin Oncol, 2010, 28(3): 466-474

[12]

RussoAL, BorgerDR, SzymonifkaJ, et al.. Mutational analysis and clinical correlation of metastatic colorectal cancer. Cancer, 2014, 120(10): 1482-1490

[13]

Di BartolomeoM, PietrantonioF, PerroneF, et al.. Lack of KRAS, NRAS, BRAF and TP53 mutations improves outcome of elderly metastatic colorectal cancer patients treated with cetuximab, oxaliplatin and UFT. Target Oncol, 2014, 9(2): 155-162

[14]

HeinemannV, von WeikersthalLF, DeckerT, et al.. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol, 2014, 15(10): 1065-1075

[15]

De RoockW, ClaesB, BernasconiD, et al.. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol, 2010, 11(8): 753-762

[16]

ProvenzaleD, JaspersonK, AhnenDJ, et al.. Colorectal Cancer Screening, Version 1.2015. J Natl Compr Canc Netw, 2015, 13(8): 959-968 quiz 68

[17]

ZlobecI, BihlMP, SchwarbH, et al.. Clinicopathological and protein characterization of BRAF- and K-RAS-mutated colorectal cancer and implications for prognosis. Int J Cancer, 2010, 127(2): 367-380

[18]

NaguibA, MitrouPN, GayLJ, et al.. Dietary, lifestyle and clinicopathological factors associated with BRAF and K-ras mutations arising in distinct subsets of colorectal cancers in the EPIC Norfolk study. BMC Cancer, 2010, 10: 99

[19]

MannanA, Hahn-StrombergV. K-ras mutations are correlated to lymph node metastasis and tumor stage, but not to the growth pattern of colon carcinoma. Apmis, 2012, 120(6): 459-468

[20]

ShenY, WangJ, HanX, et al.. Effectors of epidermal growth factor receptor pathway: the genetic profiling of KRAS, BRAF, PIK3CA, NRAS mutations in colorectal cancer characteristics and personalized medicine. PLoS One, 2013, 8(12): e81628

[21]

GuoTA, WuYC, TanC, et al.. Clinicopathologic features and prognostic value of KRAS, NRAS and BRAF mutations and DNA mismatch repair status: A single-center retrospective study of 1,834 Chinese patients with Stage I-IV colorectal cancer. Int J Cancer, 2019, 145(6): 1625-1634

[22]

FuX, HuangY, FanX, et al.. Demographic trends and KRAS/BRAF(V600E) mutations in colorectal cancer patients of South China: A single-site report. Int J Cancer, 2019, 144(9): 2109-2117

[23]

ImamuraY, LochheadP, YamauchiM, et al.. Analyses of clinicopathological, molecular, and prognostic associations of KRAS codon 61 and codon 146 mutations in colorectal cancer: cohort study and literature review. Mol Cancer, 2014, 13: 135

[24]

MartinettiD, CostanzoR, KadareS, et al.. KRAS and BRAF mutational status in colon cancer from Albanian patients. Diagn Pathol, 2014, 9: 187

[25]

WickendenJA, JinH, JohnsonM, et al.. Colorectal cancer cells with the BRAF(V600E) mutation are addicted to the ERK1/2 pathway for growth factor-independent survival and repression of BIM. Oncogene, 2008, 27(57): 7150-7161

[26]

TanYH, LiuY, EuKW, et al.. Detection of BRAF V600E mutation by pyrosequencing. Pathology, 2008, 40(3): 295-298

[27]

WangefjordS, SundstromM, ZendehrokhN, et al.. Sex differences in the prognostic significance of KRAS codons 12 and 13, and BRAF mutations in colorectal cancer: a cohort study. Biol Sex Differ, 2013, 4(1): 17

[28]

LiC, LeeKC, SchneiderEB, et al.. BRAF V600E mutation and its association with clinicopathological features of papillary thyroid cancer: a meta-analysis. J Clin Endocrinol Metab, 2012, 97(12): 4559-4570

[29]

ChenD, HuangJF, LiuK, et al.. BRAFV600E mutation and its association with clinicopathological features of colorectal cancer: a systematic review and meta-analysis. PLoS One, 2014, 9(3): e90607

[30]

YeJX, LiuY, QinY, et al.. KRAS and BRAF gene mutations and DNA mismatch repair status in Chinese colorectal carcinoma patients. World J Gastroenterol, 2015, 21(5): 1595-1605

[31]

LiouJM, WuMS, ShunCT, et al.. Mutations in BRAF correlate with poor survival of colorectal cancers in Chinese population. Int J Colorectal Dis, 2011, 26(11): 1387-1395

[32]

AhnTS, JeongD, SonMW, et al.. The BRAF mutation is associated with the prognosis in colorectal cancer. J Cancer Res Clin Oncol, 2014, 140(11): 1863-1871

[33]

TolJ, NagtegaalID, PuntCJ. BRAF mutation in metastatic colorectal cancer. N Engl J Med, 2009, 361(1): 98-99

[34]

Laurent-PuigP, CayreA, ManceauG, et al.. Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer. J Clin Oncol, 2009, 27(35): 5924-5930

[35]

RichmanSD, SeymourMT, ChambersP, et al.. KRAS and BRAF mutations in advanced colorectal cancer are associated with poor prognosis but do not preclude benefit from oxaliplatin or irinotecan: results from the MRC FOCUS trial. J Clin Oncol, 2009, 27(35): 5931-5937

[36]

Safaee ArdekaniG, JafarnejadSM, TanL, et al.. The prognostic value of BRAF mutation in colorectal cancer and melanoma: a systematic review and meta-analysis. PLoS One, 2012, 7(10): e47054

AI Summary AI Mindmap
PDF

96

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/