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CLCA4 和 MS4A12 作为原发性结直肠癌的重要基因标志物。

CLCA4 and MS4A12 as the significant gene biomarkers of primary colorectal cancer.

机构信息

Department of Medical Oncology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, Hebei 050000, P.R. China.

出版信息

Biosci Rep. 2020 Aug 28;40(8). doi: 10.1042/BSR20200963.

Abstract

BACKGROUND

Primary colorectal cancer (PCRC) is a common digestive tract cancer in the elderly. However, the treatment effect of PCRC is still limited, and the long-term survival rate is low. Therefore, further exploring the pathogenesis of PCRC, and searching for specific molecular targets for diagnosis are the development trends of precise medical treatment, which have important clinical significance.

METHODS

The public data were downloaded from Gene Expression Omnibus (GEO) database. Verification for repeatability of intra-group data was performed by Pearson's correlation test and principal component analysis. Differentially expressed genes (DEGs) between normal and PCRC were identified, and the protein-protein interaction (PPI) network was constructed. Significant module and hub genes were found in the PPI network. A total of 192 PCRC patients were recruited between 2010 and 2019 from the Fourth Hospital of Hebei Medical University. RT-PCR was used to measure the relative expression of CLCA4 and MS4A12. Furthermore, the study explored the effect of expression of CLCA4 and MS4A12 for overall survival.

RESULTS

A total of 53 DEGs were identified between PCRC and normal colorectal tissues. Ten hub genes concerned to PCRC were screened, namely CLCA4, GUCA2A, GCG, SST, MS4A12, PLP1, CHGA, PYY, VIP, and GUCA2B. The PCRC patients with low expression of CLCA4 and MS4A12 has a worse overall survival than high expression of CLCA4 and MS4A12 (P<0.05).

CONCLUSION

The research of DEGs in PCRC (53 DEGs, 10 hub genes, especially CLCA4 and MS4A12) and related signaling pathways is conducive to the differential analysis of the molecular mechanism of PCRC.

摘要

背景

原发性结直肠癌(PCRC)是老年人常见的消化道癌症。然而,PCRC 的治疗效果仍然有限,长期生存率低。因此,进一步探讨 PCRC 的发病机制,寻找特异性分子诊断靶点是精准医疗的发展趋势,具有重要的临床意义。

方法

从基因表达综合数据库(GEO)中下载公共数据。采用 Pearson 相关检验和主成分分析对组内数据的可重复性进行验证。鉴定正常与 PCRC 之间的差异表达基因(DEGs),构建蛋白质-蛋白质相互作用(PPI)网络。在 PPI 网络中找到显著模块和枢纽基因。于 2010 年至 2019 年期间,从河北医科大学第四医院招募了 192 名原发性结直肠癌患者。采用 RT-PCR 测量 CLCA4 和 MS4A12 的相对表达。进一步研究了 CLCA4 和 MS4A12 表达对总生存期的影响。

结果

在 PCRC 与正常结直肠组织之间鉴定出 53 个 DEGs。筛选出与 PCRC 相关的 10 个枢纽基因,即 CLCA4、GUCA2A、GCG、SST、MS4A12、PLP1、CHGA、PYY、VIP 和 GUCA2B。CLCA4 和 MS4A12 低表达的 PCRC 患者总生存期较 CLCA4 和 MS4A12 高表达的患者差(P<0.05)。

结论

对 PCRC(53 个 DEGs、10 个枢纽基因,尤其是 CLCA4 和 MS4A12)及相关信号通路的 DEGs 研究,有助于对 PCRC 分子机制的差异分析。

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