Investigating the obesity paradox in patients with Hepatocellular carcinomas using bioinformatics approaches

Introduction: Obesity is a heritable multifactorial disease resulted from the interplay of environmental,genetics, epigenetics, and metagenomics factors. There is a common belief that higher body mass index(BMI) is associated with reduced cancer survival. However, several studies have challenged this bydemonstrating better prognosis in overweight/obese patients, a phenomenon known as “obesity paradox”. Inthis study, we aimed to compare the genetic composition of hepatocellular carcinoma (HCC) patientswith/without overweight-obesity using whole genome sequencing data.Methods: Mutation annotation files were retrieved from TCGA-LIHC project using TCGABiolinks library.In total, ۱۵۸ normal weights and ۱۶۱ over weights/obese HCC patients were selected for downstreamanalyses. Ensembl variant effect prediction (VEP) tool was used to further annotate the identified commonand exclusive mutations in both BMI categories. In parallel, in order to find co-occurred mutations and theirfrequencies, we employed Apriori algorithm.Result: Pathogenic cancer associated mutations in TP۵۳, RYR۲, CTNNB۱, and FBN۲ were detected in bothBMI categories. Despite the presence of large number of exclusive mutations in the two BMI categories, theytarget common cancer associated pathways including TGF-beta, Notch, JAK-STAT, Wnt, Ras, MAPK,PI۳K-Akt, and p۵۳. In addition, co-occurred mutations were observed in only ۴ overweight/obese. Inaddition, the number of deaths in normal weights carrying pathogenic mutations was higher than those withoverweight/obesity (۵۲ Vs. ۴۵).Discussion: Normal weight and obese patients with HCC represent exclusive genetic mutations. However,the signaling pathways are similar. Furthermore, co-occurred mutations were not common inoverweight/obese patients. Considering high number of deaths in HCC patients with normal weight, we canconclude that overweight/obesity can protect HCC patients from worse outcomes. However, moreinvestigations considering central obesity measures are required to have correct patient categories.

کلیدواژه ها:

Hepatocellular carcinoma ، Obesity paradox ، Mutational analysis