Therapeutic Target Identification for Gastric Carcinoma caused by Helicobacter pylori through Integrated Analysis of Microarray and RNA-Seq

Abstract

Gastric cancer (GC) is the third leading cause of death worldwide where major precursor of cancer progression is infection with gastric pathogen Helicobacter pylori. 50% of the world population is infected with H.pylori pathogen where 90% of people having ulcer is due to H.pylori infection. GC is the fifth commonly diagnosed cancer whereas it is the fourth leading carcinoma in men and seventh in women. Purpose of this study is to identify potential therapeutic targets and biomarkers against H.pylori infection and GC in Homo sapiens. On publicly available H.pylori infection and GC datasets, microarray and RNA-seq analysis is performed to obtain Differentially Ex pressed Genes (DEGs). Pathway analysis is performed on the DEGs that shows their involvement in two pathways; pathways in cancer and Phosphatidyl-inositol-3-Kinase and Protein Kinase B (PI3K-AKT) signalling pathway. Further systems biology ap proaches are applied by generating a model in which DEGs that are identified through pathway analysis are used. Also, to identify therapeutic targets and biomarkers against H.pylori infection and GC. Sensitivity analysis is performed, where high sensitivity levels of Induced myeloid leukaemia cell differentiation protein (MCL-1) and Jun N-terminal Kinase (JNK) signalling is observed in H.pylori infection and GC. MCL-1 and JNK are considered as potential biomarkers and therapeutic targets for early prog nosis and diagnosis of GC. These studies can be further validated through wet lab techniques. Also, inhibitors and activators against therapeutic targets can be identified.