COLGALT1 is a Prognostic Biomarker in Clear Renal Cell Carcinoma Correlated with Immune Infiltrates: A Study Based on TCGA Data

Abstract

Background: COLGALT1, as one gene enriched in metabolic pathways, which may be related to the tumorigenesis and progression. We aim to explore the potential value of COLGALT1 in clear cell renal cell carcinoma (ccRCC) through the study.Methods: We searched The Cancer Genome Atlas (TCGA) database to collecte ccRCC patients’ information including clinicopathologic parameters and COLGALT1 gene expression. We also validiated the COLGALT1 mRNA expression by qRT-PCR. Then, We evaluated the relationship between COLGALT1 and overall survival (OS) by the Cox regression analyses. Gene Set Enrichment Analysis (GSEA) was utilized to compare between tissues with different COLGALT1 expression levels. Microsatellite Instability (MSI), Tumor Mutational Burden (TMB) and Neoantigen were evaluated through different tools. By TIMER, correlations between COLGALT1 and immune cell infiltrations were analyzed. The ESTIMATE algorithm was used to calculate the estimate, stromal and immune scores for ccRCC. Finally, CIBERSORT was carried out to explore the connection between the COLGALT1 and the tumor immune microenvironment.Results: Significant gene expression of COLGALT1 was identified between normal and ccRCC tissues. Multivariate analysis indicated that high expression of COLGALT1 was linked to poor OS (P = 0e+00). GSEA results demonstrated that high COLGALT1 expression was associated with metabolic pathways. COLGALT1 was identified to be one independent prognostic factor through the univariate and multivariate Cox regression analyses. One nomogram was integrated including both the clinicopathologic variables and COLGALT1 expression to provide a quantitative approach to clinicians for predicting prognostic risk. Futher more, we find out some genes which are significantly correlated with COLGALT1. Besides, MSI and TMB showed strong correlations with COLGALT1 in ccRCC. Also, the correlations between COLGALT1 with immune infiltrations were found in ccRCC. Finally, immune microenvironment including immune checkpoint molecules, immune cells and mismatch repair protein were proved to be linked to COLGALT1 in ccRCC.Conclusions: Our results revealed that COLGALT1 could act as a favorable prognostic factor for ccRCC. Besides, this study also provided one method to determine the immune infiltration of patients and some signal pathways which are potential regulated by COLGALT1 in ccRCC.

Whole-Exome Sequencing in Family Trios Reveals De Novo Mutations Associated with Type 1 Diabetes Mellitus

“…COLGALT1, located in 19p13.11, encodes collagen β (1-O) galactosyltransferase 1 (ColGalT1), and is associated with musculoskeletal defects, cerebral small vessel disease, and congenital porencephaly [ 77 , 78 , 79 ]. While the COLGALT1 gene is not associated with T1DM, it is correlated with autoimmune diseases as it could potentially antagonize the innate immune response [ 80 ]. The BCR gene in 22q11.23 acts as a GTPase-activating protein that encodes a novel serine/threonine kinase activity, and can be considered as a candidate tumor suppressor gene involved in meningioma pathogenesis and chronic myeloid leukemia [ 76 , 81 ].…”