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通过基因共表达网络分析鉴定结肠癌的预后基因。

Identification of Prognostic Genes for Colon Cancer through Gene Co-expression Network Analysis.

机构信息

Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.

Key Laboratory of Tumor Biological Behavior of Hubei Province, Wuhan, 430071, China.

出版信息

Curr Med Sci. 2021 Oct;41(5):1012-1022. doi: 10.1007/s11596-021-2386-2. Epub 2021 Sep 20.

Abstract

OBJECTIVE

The present study was aimed to identify novel key genes, prognostic biomarkers and molecular pathways implicated in tumorigenesis of colon cancer.

METHODS

The microarray data GSE41328 containing 10 colon cancer samples and 10 adjacent normal tissues was analyzed to identify 4763 differentially expressed genes. Meanwhile, another microarray data GSE17536 was performed for weighted gene co-expression network analysis (WGCNA).

RESULTS

In present study, 12 co-expressed gene modules associated with tumor progression were identified for further studies. The red module showed the highest association with pathological stage by Pearson's correlation analysis. Functional enrichment analysis revealed that genes in red module focused on cell division, cell proliferation, cell cycle and metabolic related pathway. Then, a total of 26 key hub genes were identified, and GEPIA database was subsequently selected for validation. Holliday junction-recognizing protein (HJURP) and cell division cycle 25 homolog C (CDC25C) were identified as effective prognosis biomarkers, which were all detrimental to prognosis. Gene set enrichment analyses (GSEA) found the two hub genes were enriched in "oocyte meiosis", "oocyte maturation that are progesterone-mediated", "p53 signaling pathway", and "cell cycle". Furthermore, the immunohistochemistry and western blotting showed that HJURP was highly expressed in colon cancer tissue.

CONCLUSION

HJURP was identified as a key gene associated with colon cancer progression and prognosis by WGCNA, which might influence the prognosis by regulating cell cycle pathways.

摘要

目的

本研究旨在鉴定结肠癌发生过程中涉及的新的关键基因、预后生物标志物和分子途径。

方法

分析包含 10 个结肠癌样本和 10 个相邻正常组织的微阵列数据 GSE41328,以鉴定 4763 个差异表达基因。同时,进行了另一个微阵列数据 GSE17536 进行加权基因共表达网络分析(WGCNA)。

结果

在本研究中,鉴定出 12 个与肿瘤进展相关的共表达基因模块进行进一步研究。Pearson 相关分析显示,红色模块与病理分期相关性最高。功能富集分析表明,红色模块中的基因主要集中在细胞分裂、细胞增殖、细胞周期和代谢相关途径。然后,鉴定出了 26 个关键枢纽基因,并随后选择 GEPIA 数据库进行验证。Holliday 连接识别蛋白(HJURP)和细胞分裂周期 25 同源物 C(CDC25C)被鉴定为有效的预后生物标志物,它们都对预后不利。基因集富集分析(GSEA)发现这两个枢纽基因富集在“卵母细胞减数分裂”、“孕酮介导的卵母细胞成熟”、“p53 信号通路”和“细胞周期”中。此外,免疫组织化学和 Western blot 显示 HJURP 在结肠癌组织中高表达。

结论

通过 WGCNA 鉴定出 HJURP 是与结肠癌进展和预后相关的关键基因,它可能通过调节细胞周期途径影响预后。

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