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通过多阶段致癌过程的转录谱分析鉴定结直肠癌中的预后基因。

Identification of prognostic genes in colorectal cancer through transcription profiling of multi-stage carcinogenesis.

作者信息

An Ning, Zhao Chen, Yu Zhuang, Yang Xue

机构信息

Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.

Department of Anatomy, School of Basic Medicine, Qingdao University, Qingdao, Shandong 266071, P.R. China.

出版信息

Oncol Lett. 2019 Jan;17(1):432-441. doi: 10.3892/ol.2018.9632. Epub 2018 Oct 29.

Abstract

Colorectal cancer is a complex multistage process following the adenoma-carcinoma sequence. Additional research on the basis of molecular dysregulations, particularly in the precancerous stage, may provide insight into the realization of potential biomarkers and therapeutic targets for the disease. In the present study, the expression profile of human multistage colorectal mucosa tissues, including healthy, adenoma and adenocarcinoma samples, was downloaded. Genes that were consistently differentially expressed in precancerous tissues and cancer samples were collected. Based on a merged biological network, the biggest connected component composed of these identified genes and their one-step neighbors were retrieved to conduct random walk with restart algorithm, in order to identify genes significantly affected during carcinogenesis. Therefore, 35 genes significantly affected by carcinogenic dysregulation were successfully identified. Survival and Cox analysis indicated that the expression of these genes was an independent prognostic factor confirmed by six cohorts. In summary, based on the transcription profile of multi-stage carcinogenesis and bioinformatics analysis, 35 genes significantly associated with patient survival were successfully identified, which may serve as promising therapeutic targets for the disease.

摘要

结直肠癌是一个遵循腺瘤-癌序列的复杂多阶段过程。基于分子失调的进一步研究,特别是在癌前阶段,可能为实现该疾病的潜在生物标志物和治疗靶点提供见解。在本研究中,下载了人类多阶段结直肠黏膜组织的表达谱,包括健康、腺瘤和腺癌样本。收集在癌前组织和癌症样本中持续差异表达的基因。基于合并的生物网络,检索由这些鉴定出的基因及其一步邻居组成的最大连通分量,以进行带重启的随机游走算法,从而识别在致癌过程中受到显著影响的基因。因此,成功鉴定出35个受致癌失调显著影响的基因。生存分析和Cox分析表明,这些基因的表达是六个队列证实的独立预后因素。总之,基于多阶段致癌的转录谱和生物信息学分析,成功鉴定出35个与患者生存显著相关的基因,它们可能成为该疾病有前景的治疗靶点。

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