WGCNA identification of CXCL13 and associated genes involved in the Tumor Immune Microenvironment (TIME) of lung adenocarcinoma

Abstract Lung cancer is the second most commonly diagnosed cancer, causing the most cancer-related deaths in the United States. Non-small cell lung cancer (NSCLC) accounts for over 75% of lung cancer cases of which lung adenocarcinoma (LUAD) is the most common. Chemokines and their receptors have been shown to be highly expressed in a number of cancers, presumably leading to abnormal signaling. Elevated levels of CXCL13, and its receptor, CXCR5, have been correlated with the overall features of mortality, but the exact mechanisms in which these factors act to promote NSCLC progression are not fully understood. Here, we studied the role of CXCL13, CXCR5, and associated genes expressed in NSCLC tumor immune microenvironment (TIME). The software package WGCNA was used to establish clusters of highly correlated genes related to clinical characteristics. A total of 23,329 transcripts were used to identify 37 modules (gene co-expression networks). The light-cyan module, consisting of 491 genes contained both CXCR5 and CXCL13. The light-cyan module is a hub gene heavy module with the top 300 transcripts exceeding our hub gene threshold (kMe > 0.6). The light-cyan module transcripts where negatively correlated with age. The top biological processes associated with the light-cyan module include immune system processes, regulation of lymphocyte activation, regulation of immune response and cellular defense response. Collectively, the gene clusters identified along with their clinical correlates provide a novel insight into the complex biology of NSCLC and its TIME.