Identification of IMPA2 as the hub gene associated with colorectal cancer and liver metastasis by integrated bioinformatics analysis.

Abstract

BACKGROUND AND OBJECTIVES:

Colorectal cancer (CRC) is one of the most common malignant tumors worldwide with high incidence and mortality rate, while colorectal liver metastasis (CRLM) is one of the major causes of cancer-related deaths. Therefore, the present study aims to identify the hub gene associated with CRC carcinogenesis and liver metastasis, and then explore its diagnostic and prognostic value as well as the potential regulation mechanism.

METHODS:

The overlapping differential co-expression genes among CRC, CRLM, and normal tissues were explored on the GSE49355 and GSE81582 datasets from the Gene Expression Omnibus (GEO) database by integrated bioinformatics analysis. Then, the hub prognostic genes were selected from the overlapping genes by univariate Cox proportional hazard analysis and online database Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Subsequently, the clinical value of the hub genes was evaluated in the TCGA and GSE39582 cohorts. Finally, the underlying mechanisms of the hub gene regulating CRC carcinogenesis and metastasis were explored by Gene function annotation and DNA methylation analysis.

RESULTS:

Inositol mono-phosphatase 2 (IMPA2) was identified as the hub gene associated with CRC carcinogenesis and liver metastasis. IMPA2 had an excellent diagnostic efficiency, and its expression was significantly decreased in CRC and liver metastasis samples, being positively correlated with poor prognosis. Moreover, its low expression was associated with AJCC stage III+IV, T4, N1+2, and M1. In addition, our results revealed that the potential mechanisms used by IMPA2 to mediate CRC carcinogenesis and metastasis could be associated with lipid metabolism and epithelial mesenchymal transition (EMT). Finally, IMPA2 expression could be regulated by DNA methylation.

CONCLUSIONS:

IMPA2 was identified and reported for the first time as a hub gene biomarker in the diagnosis and prognosis of CRC, which could regulate CRC carcinogenesis and liver metastasis through the regulation of lipid metabolism, EMT, and DNA methylation.

• Authors: Liuli Wang, Deming Liu, Shuo Liu, Tianyi Liao, Yajun Jiao, Xianglai Jiang, Yongfeng Wang, Yaqiong Chen, Haizhong Ma, Hui Cai
• Journal: Translational oncology (Transl Oncol) Vol. 21 Pg. 101435 (Jul 2022) ISSN: 1936-5233 [Print] United States
• PMID: 35483170 (Publication Type: Journal Article)
• Copyright: Copyright © 2022. Published by Elsevier Inc.