A novel prognostic signature contributes to precision treatment in colon adenocarcinoma with KRAS mutation

克拉斯 列线图 结直肠癌 比例危险模型 医学 肿瘤科 内科学 腺癌 癌症 接收机工作特性 基因签名 癌症研究 生物 基因 遗传学 基因表达
作者
Weiwei Dong,He Zhang,Qingyan Li,Na Guan,Sheng Wang,Huixia Zhao,Xiyan Zhang,Zhiyan Zeng,Yanyan Hu,Qiuwen Li,Jingwen Yang,Zihuan Ma,Mei‐Ling Chen,Wenhua Xiao
出处
期刊:European Journal of Cancer Prevention [Lippincott Williams & Wilkins]
卷期号:32 (6): 557-565 被引量:1
标识
DOI:10.1097/cej.0000000000000819
摘要

Approximately 40% of colon cancer harbor Kirsten rat sarcoma viral oncogene ( KRAS ) mutations, but the prognostic value of KRAS mutations in colon cancer is still controversial.We enrolled 412 colon adenocarcinoma (COAD) patients with KRAS mutations, 644 COAD patients with KRAS wild-type and 357 COAD patients lacking information on KRAS status from five independent cohorts. A random forest model was developed to estimate the KRAS status. The prognostic signature was established using least absolute shrinkage and selection operator-Cox regression and evaluated by Kaplan-Meier survival analysis, multivariate-Cox analysis, receiver operating characteristic curve and nomogram. The expression data of KRAS -mutant COAD cell lines from the Cancer Cell Line Encyclopedia database and the corresponding drug sensitivity data from the Genomics of Drug Sensitivity in Cancer database were used for potential target and agent exploration.We established a 36-gene prognostic signature classifying the KRAS -mutant COAD as high and low risk. High risk patients had inferior prognoses compared to those with low risk, while the signature failed to distinguish the prognosis of COAD with KRAS wild-type. The risk score was the independent prognostic factor for KRAS -mutant COAD and we further fabricated the nomograms with good predictive efficiency. Moreover, we suggested FMNL1 as a potential drug target and three drugs as potential therapeutic agents for KRAS -mutant COAD with high risk.We established a precise 36-gene prognostic signature with great performance in prognosis prediction of KRAS -mutant COAD providing a new strategy for personalized prognosis management and precision treatment for KRAS -mutant COAD.
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