PTPN11 is a potential biomarker for type 2 diabetes mellitus complicated with colorectal cancer

• Published in: Scientific reports 2024-10, Vol.14 (1), p.25155-17, Article 25155
• Main Authors: Sun, Meiling, Han, Zhe, Luo, Zhimin, Ge, Lijuan, Zhang, Xiaolin, Feng, Keshu, Zhang, Guoshan, Xu, Fuyi, Zhou, Hongpan, Han, Hailin, Jiang, Wenguo
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; 631/250; 631/67; 692/308; AKT protein; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer; Cell cycle; Cell growth; Cell Line, Tumor; Cell migration; Cell Proliferation; Colorectal cancer; Colorectal cancer (CRC); Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Cyclin D; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - metabolism; Epidemiology; Female; Gene Expression Regulation, Neoplastic; Gene set enrichment analysis; Genomic analysis; Glycolysis; Humanities and Social Sciences; Humans; Insulin secretion; Male; Malignancy; Metabolic pathways; Metabolism; Middle Aged; multidisciplinary; Oxidative phosphorylation; Patients; Phosphorylation; Prognosis; Protein Tyrosine Phosphatase, Non-Receptor Type 11 - genetics; Protein Tyrosine Phosphatase, Non-Receptor Type 11 - metabolism; Proteins; PTPN11; Science; Science (multidisciplinary); Signal Transduction; Tissues; Tumors; Type 2 diabetes mellitus (T2DM); Western blotting; Wound healing
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-75889-x

Epidemiological surveys have shown that the incidence of type 2 diabetes mellitus (T2DM) and malignancies is rapidly increasing worldwide and has become a major disease that threatens human life. In this study, we quantitatively analyzed the proteome of tumor tissues and adjacent normal tissues from six patients withT2DM combined with colorectal cancer (CRC) and eight non-diabetic CRC, focusing on the effect of T2DM on tumor tissues. We analyzed the functional enrichment of differentially expressed proteins (DEPs) using clusterProfiler in R and the expression level of protein tyrosine phosphatase non-receptor type 11 (PTPN11) and other key proteins in the TIMER and GEPIA2 databases. The HPA database was used to validate PTPN11 protein expression. The correlation between PTPN11 expression and clinicopathological features was analyzed by UALCAN database. The impact of PTPN11 on clinical prognosis was evaluated utilizing Kaplan-Meier Plotter. The correlation between PTPN11 expression and tumor-infiltrated immune cells was investigated via TIMER and TISIDB databases. Gene set enrichment analysis (GSEA) was performed to examined the pathway of PTPN11 enrichment in CRC using data from The Cancer Genome Atlas (TCGA) database. Furthermore, small interfering (si) RNA was used to knock down PTPN11 in CRC cell line SW480. Western blot analysis was used to detect PTPN11 expression in tissue samples or cells and the effect of PTPN11 knockdown on key proteins related to PI3K/AKT and cell cycle pathway in SW480 cells. Cell proliferation and wound healing assays were used to detect the effects of cell proliferation and migration after knockdown of PTPN11 or treatment with high glucose. We found that metabolic pathways such as oxidative phosphorylation, glycolysis/gluconeogenesis, and insulin secretion were significantly enriched in tumor tissues from diabetic patients compared to non-diabetic patients. In addition, PTPN11, a marker gene associated with T2DM and CRC, were mined in diabetic tumor tissues. PTPN11 showed high expression in diabetic tumor tissues compared to normal tissues. High PTPN11 expression predicted poor prognosis in CRC. PTPN11 expression was strongly associated with immune infiltrating cells in CRC. GSEA analysis revealed that PTPN11 was enriched in cancer-related pathways. Western blotting analysis indicated that PTPN11 knockdown reduced the protein levels of p-PI3K, p-AKT, CDK1 and CYCLIN D, without altering PI3K and AKT protein levels. Cell prolife