Lymphatic invasion (LI) is an early event of metastasis and closely associated with overall survival in colon adenocarcinoma (COAD). Our aim was to gain deeper insight into the mechanism of lymphatic invasion in COAD. Subtype-specific somatic mutations and differentially expressed genes (DEGs) screening were based on The Cancer Genome Atlas (TCGA). Gene Ontology (GO) enrichment analysis was utilized to explore the biological function. The condition of tumor-infiltrating lymphocytes was performed by TIMER online database. Survival analysis was based on Kaplan-Meier curve method. Lymphatic invasion was associated with poor prognosis of patients with COAD. Nine mutations were enriched in lymphatic invasion-negative group. A total of 50 were differentially expressed between LI-positive tissues and LI-negative tissues. The DEGs were enriched in lipoprotein-related functions. MUC4 in-frame deletion at A4166-S4181 was associated with favorable prognosis of COAD patients. BMPR2 frameshift mutation g.chr2:202555407delA played cis and trans functions in downregulation of itself and CTLA4 upregulation. And it was associated with higher mutational burden. LAMP5, CUBN and TCHH were DEGs associated with prognosis and abundance of tumor-infiltrating lymphocytes. In conclusion, our study provides LI-associated genetic and transcriptional alterations, which helps to better understand the potential mechanisms and microenvironment in COAD.
Keywords: Bone morphogenetic protein (BMP) signaling pathway; Colon adenocarcinoma; Lymphatic invasion; Tumor-infiltrating lymphocytes.
Copyright © 2020. Published by Elsevier B.V.