Gender Dimorphism in Hepatic Carcinogenesis-Related Gene Expression Associated with Obesity as a Low-Grade Chronic Inflammatory Disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) show clear evidence of sexual dimorphism, with a significantly higher incidence in males. Among the determining factors that could explain this sex-based difference, the specific distribution of fat by sex has been suggested as a primary candidate, since obesity is a relevant risk factor. In this context, obesity, considered a low-grade chronic inflammatory pathology and responsible for the promotion of liver disease, could lead to sexual dimorphism in the expression profile of genes related to tumor development. When we compared the expression levels of genes associated with the early stages of carcinogenesis in the liver between male and female diet-induced obesity (DIO) rats, we observed that the expression pattern was similar in obese male and female animals. Interestingly, the SURVIVIN/BIRC5 oncogene showed a higher expression in male DIO rats than in female DIO and lean rats. This trend related to sexual dimorphism was observed in leukocytes from patients with obesity, although the difference was not statistically significant. In conclusion, this study evidenced a similar pattern in the expression of most carcinogenesis-related genes in the liver, except SUVIVIN/BIRC5, which could be a predictive biomarker of liver carcinogenesis predisposition in male patients with obesity.

Comprehensive review on sexual dimorphism to improve scalp acupuncture in nervous system disease

“…Additionally, there are differences in physiological and pathological changes between the sexes. There are many pathological processes, disease incidence, prevalence, and mortality parameters associated with SD in mammals 31,32 . Experiments with diet‐induced obesity found sex‐and age‐dependent changes in the adiponectin/leptin ratio 33 .…”

“…There are many pathological processes, disease incidence, prevalence, and mortality parameters associated with SD in mammals. 31 , 32 Experiments with diet‐induced obesity found sex‐and age‐dependent changes in the adiponectin/leptin ratio. 33 It is noteworthy that obese mice react differently to obesity and metabolic disorders based on gender and age.…”

Exploiting gender-based biomarkers and drug targets: advancing personalized therapeutic strategies in hepatocellular carcinoma

“…The liver is a tissue that bears additional sex-specific risk factors, one being alcohol consumption and obesity for the development of HCC. Some sex-specific risk factors, including alcohol intake, obesity, and insulin resistance, have been implicated in hepatocarcinogenesis, likely due to sex differences in alcohol metabolism and fat distribution impacting susceptibility to HCC (D'Souza et al, 2020;Izquierdo et al, 2022;Kardashian et al, 2023). That highlights the pressing need for a transition to a gender perspective in the entire flow of liver cancer research, from epidemiological inquiry to molecular analysis.…”