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Comprehensive analysis of location-specific hub genes related to the pathogenesis of colon cancer

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Abstract

The molecular mechanisms underlying colon cancer lesions at different sites are not entirely clear. Herein, we aimed to explore location-specific gene profiles related to the pathogenesis of colon cancer and to identify their function. The robust rank aggregation (RRA) method was used to integrate colon cancer microarray datasets and screen differentially expressed gene (DEG) profiles between left- and right-sided colon cancers. Then, weighted gene co-expression network analysis (WGCNA) was performed to cluster the DEGs into modules and identify hub genes. The selected hub genes were validated using The Cancer Genome Atlas dataset and clinical tissues. We assessed the association of selected hub genes with the methylation status in immune cells. In total, 905 DEGs were identified by RRA; five gene modules and 18 hub genes were related to the clinical traits of colon cancer by WGCNA. Four hub genes were selected and shown to be associated with colon cancers on different sides and distant metastasis in the validation analysis. The four hub genes showed a low methylation status, and their expression was significantly associated with methylation status. Positive correlations were observed between the four hub genes and tumor purity and among the four types of immune cells. Gene set enrichment analysis revealed that the four hub genes were mainly involved in two cancer-related pathways. In conclusion, this study identified a set of location-specific genes related to the pathogenesis of colon cancer. These four hub genes may act as novel candidate targets for the treatment of colon cancer.

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Data availability

The datasets used during the present study are available from the corresponding author upon reasonable request. All raw data of COAD can be downloaded freely from TCGA database and GEO database.

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Acknowledgements

This study was partially supported by National Natural Science Foundation (No. 81260083), Natural Science Foundation of Guangxi (No. 2018JJA140136), and Guangxi University Students Innovation and Entrepreneurship Project (WLXSZX19039; 201910598012; 201910598241). Guangxi Medical Scientific Research Project (Z20200334)

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Author notes

  1. Cheng Shi, Ke Ding and Ke-zhi Li have contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology, People’s Hospital of Liuzhou, Liuzhou, 545006, China

    Cheng Shi

  2. Department of Radiology, Third Affiliated Hospital of Guangxi Medical University, Nanning, 530031, China

    Ke Ding

  3. Department of Research, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Nanning, 530021, China

    Ke-zhi Li, Long Long, Ji-lin Li & Bang-li Hu

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  1. Cheng Shi
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Contributions

Study concept and design: SC and HBL; Collection and assembly of data: SC and LKZ; Performed the experiment: LKZ and LJL; Data analysis and interpretation: HBL, LL, and LKZ; Revised the manuscript: DK, SC; Manuscript writing and review: All authors.

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Correspondence to Bang-li Hu.

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Shi, C., Ding, K., Li, Kz. et al. Comprehensive analysis of location-specific hub genes related to the pathogenesis of colon cancer. Med Oncol 37, 77 (2020). https://doi.org/10.1007/s12032-020-01402-9

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