1st International and 10th National Iranian Conference on Bioinformatics
Home Accepted Papers
Investigating the obesity paradox in patients with Hepatocellular carcinomas using bioinformatics approaches
Paper ID : 1155-ICB10
Authors:
Nazanin Hosseinkhan *1, Zahra Narimani2, Laily Najafi3, Mohammad Ebrahim Khamseh3
1Research institute of endocrinology and metabolism, Iran University of Medical Sciences
2Department of Computer Science and Information Technology, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, Iran
3Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
Abstract:
Introduction: Obesity is a heritable multifactorial disease resulted from the interplay of environmental, genetics, epigenetics, and metagenomics factors (1). There is a common belief that higher body mass index (BMI) is associated with reduced cancer survival. However, several studies have challenged this by demonstrating better prognosis in overweight/obese patients, a phenomenon known as “obesity paradox” (2). In this study, we aimed to compare the genetic composition of hepatocellular carcinoma (HCC) patients with/without overweight-obesity using whole genome sequencing data.
Methods: Mutation annotation files were retrieved from TCGA-LIHC project using TCGABiolinks (3) library. In total, 158 normal weights and 161 over weights/obese HCC patients were selected for downstream analyses. Ensembl variant effect prediction (VEP) tool was used to further annotate the identified common and exclusive mutations in both BMI categories. In parallel, in order to find co-occurred mutations and their frequencies, we employed Apriori algorithm (4).
Result: Pathogenic cancer associated mutations in TP53, RYR2, CTNNB1, and FBN2 were detected in both BMI categories. Despite the presence of large number of exclusive mutations in the two BMI categories, they target common cancer associated pathways including TGF-beta, Notch, JAK-STAT, Wnt, Ras, MAPK, PI3K-Akt, and p53. In addition, co-occurred mutations were observed in only 4 overweight/obese. In addition, the number of deaths in normal weights carrying pathogenic mutations was higher than those with overweight/obesity (52 Vs. 45).
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 in overweight/obese patients. Considering high number of deaths in HCC patients with normal weight, we can conclude that overweight/obesity can protect HCC patients from worse outcomes. However, more investigations considering central obesity measures are required to have correct patient categories.
Keywords:
Hepatocellular carcinoma, Obesity paradox, Mutational analysis
Status : Paper Accepted (Oral Presentation)