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BRAF和KRAS突变对伊朗结直肠癌患者生存的预后价值:与微卫星不稳定性相关

Prognostic Value of BRAF and KRAS Mutation in Relation to Colorectal Cancer Survival in Iranian Patients: Correlated to Microsatellite Instability.

作者信息

Nazemalhosseini-Mojarad Ehsan, Kishani Farahani Roya, Mehrizi Maryam, Baghaei Kaveh, Yaghoob Taleghani Mohammad, Golmohammadi Mina, Peyravian Noshad, Ashtari Sara, Pourhoseingholi Mohmad Amin, Asadzadeh Aghdaei Hamid, Zali Mohammad Reza

机构信息

Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Erabi Ave, P.O. Box 1985717413, Tehran, Velenjak, Iran.

出版信息

J Gastrointest Cancer. 2020 Mar;51(1):53-62. doi: 10.1007/s12029-019-00201-4.

Abstract

PURPOSE

To evaluate the prognostic role of BRAF and KRAS mutations after adjustment for microsatellite instability (MSI) in Iranian colorectal cancer (CRC) patients.

METHODS

BRAF and KRAS mutations and MSI status were assessed in 258 Iranian subjects with CRC. Two hundred fifty-eight consecutive stages I-IV CRC patients, who underwent surgical resection of adenocarcinoma from 2012 to 2016, were enrolled in the research. Pyrosequencing and Cast-PCR methods were used to the detection of KRAS and BRAF mutations. Kaplan-Meier and Cox regression were employed to estimate hazard ratios (HR) for the association between BRAF and KRAS mutation and overall survival (OS).

RESULTS

KRAS and BRAF mutations were detected in 36 (14%) and 15 (5.8%) cases of 258 patients with CRC, respectively. BRAF mutations that all comprised V600E and KRAS mutations was found in codon 12 and 13 (80.6% and 19.4%), respectively. KRAS mutations were detected in 19 (15.4%) patients of 123 microsatellite stable (MSS) CRC and it is significantly associated with tumor location and metastasis. BRAF and KRAS mutant vs. wild type of BRAF and KRAS, 5-year OS was 73.3% vs. 82.3% and 83.3% vs. 81.5% (long-rank P > 0.05), respectively. KRAS mutant vs. KRAS-wild-type tumors in MSS/MSI-L status CRC patients, 5-year OS was 78.9% vs. 90.4% (long-rank p = 0.046).

CONCLUSION

The present study revealed that BRAF and KRAS mutations were not related to the worse overall survival, while KRAS mutation can be a prognostic factor for overall survival in sporadic microsatellite-stable (MSS) status in Iranian CRC patients.

摘要

目的

评估在调整微卫星不稳定性(MSI)后,BRAF和KRAS突变对伊朗结直肠癌(CRC)患者的预后作用。

方法

对258名伊朗CRC患者进行BRAF和KRAS突变以及MSI状态评估。连续纳入2012年至2016年期间接受腺癌手术切除的258例I-IV期CRC患者参与研究。采用焦磷酸测序和Cast-PCR方法检测KRAS和BRAF突变。采用Kaplan-Meier法和Cox回归分析评估BRAF和KRAS突变与总生存期(OS)之间关联的风险比(HR)。

结果

258例CRC患者中,分别有36例(14%)和15例(5.8%)检测到KRAS和BRAF突变。BRAF突变均为V600E,KRAS突变分别位于第12和13密码子(80.6%和19.4%)。在123例微卫星稳定(MSS)CRC患者中,有19例(15.4%)检测到KRAS突变,且其与肿瘤位置和转移显著相关。BRAF和KRAS突变型与BRAF和KRAS野生型相比,5年总生存率分别为73.3%对82.3%以及83.3%对81.5%(对数秩P>0.05)。在MSS/MSI-L状态的CRC患者中,KRAS突变型与KRAS野生型肿瘤相比,5年总生存率为78.9%对90.4%(对数秩p=0.046)。

结论

本研究表明,BRAF和KRAS突变与较差的总生存期无关,而KRAS突变可能是伊朗CRC患者散发性微卫星稳定(MSS)状态下总生存期的一个预后因素。

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