Gene coexpression network analysis of multiple cancers discovers the varying stem cell features between gastric and breast cancer

Abstract

Several decades of research efforts gave a very good platform of genomic data repository for the researchers to study the gene expression and interactions of cancer samples. The analysis of genomic data in large scale provides a global view on dysregulation of molecular mechanisms in cancer. The conserved cancer hallmarks in prior studies motivated the researchers to identify the common molecular changes across cancers. In this study the mRNA profile data of gastric, colon, liver and breast were studied. Weighted gene co-expression network analysis (WGCNA) of four cancers has identified coexpressed and conserved modules in all four cancers. The conserved module depicts the major cellular mechanisms like immune response, extracellular matrix, mesenchymal stem cell, dream complex, cell cycle and embryonic stem cell. Intensive screening of the genes related to mesenchymal and embryonic stem cell has made a striking finding that the presence of stem cell properties in gastric and breast cancers is varying during the cancer progression. The change in expression of stem cell associated genes from grade II to grade III cancer samples are showing inverse relationship between gastric and breast cancers. Mesenchymal stem cell related genes are enriched in grade III gastric tumour samples, and in breast cancer it is enriched in grade II. On the other hand the embryonic stem cell related genes are enriched in grade II sample types of gastric tumour and in case of breast cancer it is enriched in grade III. The result of this study is integrative of two important cancer factors, the grade and stem cell properties. This finding unveils, the occurrence of stem cell properties in cancer, differ in grades. Hence, for remarkable results studies in cancer stem cell might be diverted and concentrated from single stem cell to mesenchymal and embryonic cells. This study hypothesize that varying stem cell properties during cancer progression might be a better concordance among the shared tumour cell properties defined as hallmark of cancer.