Identification of Hub Gene TIMP1 and Relative ceRNAs Regulatory Network in Colorectal Cancer

Ya-Fei Qin; Guang-Ming Li; Grace Wang; De-Jun Kong; Hong-Da Wang; Yi-Ming Zhao; Jing-Peng Hao; Hong Qin; Da-Qing Sun; Hao Wang

doi:10.2147/TCRM.S321101

Identification of Hub Gene TIMP1 and Relative ceRNAs Regulatory Network in Colorectal Cancer

Ther Clin Risk Manag. 2021 Aug 27:17:889-901. doi: 10.2147/TCRM.S321101. eCollection 2021.

Authors

Ya-Fei Qin^{1

2}, Guang-Ming Li^{1

2}, Grace Wang³, De-Jun Kong^{1

2}, Hong-Da Wang^{1

2}, Yi-Ming Zhao^{1

2}, Jing-Peng Hao⁴, Hong Qin^{1

2}, Da-Qing Sun⁵, Hao Wang^{1

2}

Affiliations

¹ Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.
² Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.
³ Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁴ Department of Anorectal Surgery, The Second Hospital of Tianjin Medical University, Tianjin, People's Republic of China.
⁵ Department of Pediatric Surgery, Tianjin Medical University, Tianjin, People's Republic of China.

Abstract

Objective: This study aimed to discover the ceRNAs network in the pathophysiological development of human colorectal cancer (CRC) and to screen biomarkers for target therapy and prognosis by using integrated bioinformatics analysis.

Methods: Data on gene expressions of mRNAs, miRNAs, and circRNAs and clinical information were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases, respectively. Differentially expressed mRNAs (DEmRNAs) were identified by using the DESeq2 package of R software. Functional enrichment analysis was conducted using the ClusterProfiler package of R software. The protein-protein interaction (PPI) network was shown by the STRING website. Survival analysis of hub genes was performed using the survival package in R software. Interactions among hub genes, differentially expressed miRNAs (DEmiRNAs), and differentially expressed circRNAs (DEcircRNAs) were used to construct the ceRNAs network.

Results: A total of 412 DEmRNAs including 82 upregulated and 330 downregulated genes were screened out between 473 CRC and 41 normal samples. Two hundred and sixty DEcircRNAs including 253 upregulated and 7 downregulated genes were altered between 23 CRC and 23 normal samples. One hundred and ninety DEmiRNAs including 82 upregulated and 108 downregulated genes were obtained between 450 CRC and 8 normal samples. A ceRNAs and PPI network were successfully constructed, and TIMP1 associated with prognosis was employed.

Conclusion: The present study identified a novel circRNAs-miRNAs-mRNA ceRNAs network, which implied that TIMP1 and related miRNAs, circRNAs were potential biomarkers underlying the development of CRC, providing new insights for survival predictions and therapeutic targets.

Keywords: TIMP1; bioinformatic analysis; ceRNAs; circRNAs; colorectal cancer.

Grants and funding

This work was supported by grants to Hao Wang from the National Natural Science Foundation of China (No. 82071802), Tianjin Application Basis and Cutting-Edge Technology Research Grant (No. 14JCZDJC35700), Li Jieshou Intestinal Barrier Research Special Fund (No. LJS_201412), Natural Science Foundation of Tianjin (No. 18JCZDJC35800), and Tianjin Medical University Talent Fund; by a grant to Dejun Kong from Tianjin Research Innovation Project for postgraduate students (No. 2019YJSS184).