Co-pathogenic genes and potential common molecular mechanisms of type 2 diabetes mellitus, obesity, nonalcoholic steatohepatitis, and polycystic ovary syndrome

doi:10.3877/cma.j.issn.1674-0785.2024.05.007

Abstract

Abstract:

Objective

To explore the co-pathogenic genes and potential common molecular mechanisms of type 2 diabetes mellitus (T2DM), obesity, nonalcoholic steatohepatitis (NASH), and polycystic ovary syndrome (PCOS).

Methods

The gene expression datasets GSE20966, GSE17470, GSE88837, and GSE34526 were downloaded from the GEO database, and differentially expressed genes were identified with limma package. Then, the four groups of differentially expressed genes were intersected, and function enrichment analysis was performed to construct a protein-protein interaction (PPI) network. CIBERSORT algorithm was used to analyze the RNA-seq data of different patients, so as to infer the relative proportion of 22 kinds of immune infiltrating cells. GSVA algorithm was used to comprehensively score each gene set and evaluate the potential biological function changes of different samples.

Results

Five intersecting genes were identified, namely, PTPN3, GBP2, ARL1, NEDD4L, and PTPN11. PTPN11, NEDD4L, and GBP2 are related to insulin-related pathways. Furthermore, the specific signal pathways involved in the three core genes were verified by GSVA, which showed that the high expression of GBP2 is related to P53 PATHWAY, KRAS SIGNALING, APOPTOSIS, and other signal pathways. The high expression of NEDD4L is related to G2M CHECKPOINT, TGF BETA SIGNALING, and ADIPOGENESIS. High expression of PTPN11 is related to PROTEIN SECRETION, ADIPOGENESIS, FATTY ACID METABOLISM, and other signal pathways.

Conclusion

The newly discovered comorbid genes and the related metabolic signal pathways in T2DM, obesity, NASH, and PCOS provide new targets and biomarkers for their treatment and diagnosis.

Key words: Type 2 diabetes, Obesity, Nonalcoholic steatohepatitis, Polycystic ovary syndrome, Pathogenic factor

Xing Wang, Yuan Chen, , Wusman Rezi Wan Guli, Yanying Guo. Co-pathogenic genes and potential common molecular mechanisms of type 2 diabetes mellitus, obesity, nonalcoholic steatohepatitis, and polycystic ovary syndrome[J]. Chinese Journal of Clinicians(Electronic Edition), 2024, 18(05): 481-490.

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URL: https://zhlcyszz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-0785.2024.05.007

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Figures/Tables 11

References 39

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