The underlying pathophysiology association between the Type 2‐diabetic and hepatocellular carcinoma

Abstract

Type 2‐diabetic (T2D) disease has been reported to increase the incidence of liver cancer, however, the underlying pathophysiology is still not fully understood. Here, we aimed to reveal the underlying pathophysiology association between the T2D and hepatocellular carcinoma (HCC) and, therefore, to find the possible therapeutic targets in the occurrence and development of HCC. The methylation microarray data of T2D and HCC were extracted from the Gene Expression Omnibus and The Cancer Genome Atlas. A total of 504 differentially methylated genes (DMGs) between T2D samples and the controls were identified, whereas 6269 DMGs were identified between HCC samples and the control groups. There were 336 DMGs coexisting in diabetes and HCC, among which 86 genes were comethylated genes. These genes were mostly enriched in pathways as glycosaminoglycan biosynthesis, fatty acid, and metabolic pathway as glycosaminoglycan degradation and thiamine, fructose and mannose. There were 250 DMGs that had differential methylation direction between T2D DMGs and HCC DMGs, and these genes were enriched in the Sphingolipid metabolism pathway and immune pathways through natural killer cell‐mediated cytotoxicity and ak‐STAT signaling pathway. Eight genes were found related to the occurrence and development of diabetes and HCC. Moreover, the result of protein‐protein interaction network showed that CDKN1A gene was related to the prognosis of HCC. In summary, eight genes were found to be associated with the development of HCC and CDKN1A may serve as the potential prognostic gene for HCC.

Glucose promotes epithelial‐mesenchymal transitions in bladder cancer by regulating the functions of YAP1 and TAZ

“…Due to the high‐glucose consumption of cancer cells, cancer progression is positively associated with impaired energy metabolism 19 . T2D is characterized by high blood glucose levels and is positively correlated with the initiation, promotion and progression of various human cancers 7,8 . High‐glucose levels can impair angiotensinogen and enhance breast cancer proliferation and metastasis 20 .…”

“…Type 2 diabetes (T2D) has been implicated in the development of several types of cancer, including liver cancer 7 and BC 8 . Previous studies have demonstrated that high‐glucose levels may promote EMTs.…”

Prognostic Values of Stabilin-2 in Hepatocellular Carcinoma

“…In a previous study, stichopus japonicus acid mucopolysaccharide (SJAMP) effectively inhibited the growth of HCC through the stimulation of immune organs and tissue proliferation [44]. In addition, inhibitors of glycosaminoglycan biosynthesis may affect liver metastasis potential of tumor cells [45]. The proteoglycan composed of protein core and glycosaminoglycan chain plays a vital role in the development of HCC, and is been explored as a potential HCC biomarker and therapeutic target [46].…”

Hepatocellular Carcinoma and Obesity, Type 2 Diabetes Mellitus, Cardiovascular Disease: Causing Factors, Molecular Links, and Treatment Options

“…Some differentially methylated genes (DMGs) were co-expressed in HCC and T2DM, such as ST3 beta-galactoside alpha-2,3-sialyltransferase 2 (ST3GAL2) and glycerophosphodiester phosphodiesterase domain containing 2 (GDPD2). And also, these DMGs were implicated in the signaling pathways including biosynthesis of glycosaminoglycan and unsaturated fatty acids ( 51 ). In addition, patients with NAFLD showed a higher risk of incident T2DM than those without NAFLD, even more in those with advanced high NAFLD fibrosis scores ( 52 ).…”