Investigate the Link Between Abdominal Obesity and Lung Cancer: Based on Transcriptomic Data and Ge-nome-Scale Metabolic Model

Background: Obesity is one of the critical health issues world-wide, and the evidence base for a link between obesity and cancer is growing. There is emerging evidence that general obesity and/ or abdominal obesity is associated with increased risk of certain types of cancers, including breast cancer, colorectal, endometri-al, esophagus, kidney, pancreatic, thyroid, gallbladder and lung cancer. Several meta-analyses of observational studies have been performed to examine the association between abdominal obe-sity and lung cancer. Systems biology approaches, based on the integration of various data types leading to computational and mathematical modeling, are particularly suitable for investigat-ing the underlying molecular mechanisms of complex diseases. Materials and Methods: The Genome-scale metabolic model of the human adipocyte, iAdipocytes1809 , was downloaded from the Human Metabolic Atlas database in the compressed Systems Biology Markup Language (SBML) format. Gene ex-pression data were extracted from the dataset GSE78958 depos-ited at the Gene Expression Omnibus portal. Raw data, in CEL format, were imported, corrected, transformed and normalized through GEOquery and Affy R packages.Results: In this work, we exploited gene expression data of lung cancer obese and lean patients to simulate a curated genome-scale metabolic model of the human adipocyte, avail-able in the Human Metabolic Atlas database. We performed a network topology differential analysis to search for pattern differences and identify the principal reactions associated with significant changes across the two conditions under study. In particular, we show that the qualitative and quantitative assess-ment of metabolic fluxes modulated by gene expression data provides a valuable method for investigating the mechanisms associated with the phenotype under study, and can foster our interpretation of biological phenomena.Conclusion: As a case study, we investigated the relationship between abdominal obesity and lung cancer. In summary, ab-dominal obesity may play an important role in the development of lung cancer.

کلیدواژه ها:

Abdominal Obesity ، Lung Cancer ، Genome-Scale Metabolic Model