Association of Elevated Expression Levels of COL4A1 in Stromal Cells with an Immunosuppressive Tumor Microenvironment in Low-Grade Glioma, Pancreatic Adenocarcinoma, Skin Cutaneous Melanoma, and Stomach Adenocarcinoma.

Aberrant expression of collagen type IV alpha chain 1 (COL4A1) can influence tumor cell behavior. To examine the association of COL4A1 expression in the tumor microenvironment (TME) with tumor progression, we performed bioinformatics analyses of The Cancer Genome Atlas RNA sequencing and RNA microarray datasets available in public databases and identified upregulated COL4A1 expression in most examined tumor types compared to their normal counterparts. The elevated expression of COL4A1 was correlated with low survival rates of patients with low-grade glioma, pancreatic adenocarcinoma, skin cutaneous melanoma, and stomach adenocarcinoma, thus suggesting its potential use as a biomarker for the poor prognosis of these tumors. However, COL4A1 was mostly expressed in adjacent stromal cells, such as cancer-associated fibroblasts (CAFs) and endothelial cells. Additionally, COL4A1 expression was highly correlated with the signatures of CAFs and endothelial cells in all four tumor types. The expression of marker genes for the infiltration of pro-tumoral immune cells, such as Treg, M2, and TAM, and those of immunosuppressive cytokines exhibited very strong positive correlations with COL4A1 expression. Collectively, our data suggest that COL4A1 overexpression in stromal cells may be a potential regulator of tumor-supporting TME composition associated with poor prognosis.

Multiomic Analysis of Cereblon Expression and Its Prognostic Value in Kidney Renal Clear Cell Carcinoma, Lung Adenocarcinoma, and Skin Cutaneous Melanoma.

Cereblon (CRBN) is a component of the E3 ubiquitin ligase complex that plays crucial roles in various cellular processes. However, no systematic studies on the expression and functions of CRBN in solid tumors have been conducted to date. Here, we analyzed CRBN expression and its clinical value using several bioinformatic databases. CRBN mRNA expression was downregulated in various cancer types compared to normal cells. Survival analysis demonstrated that overall survival was significantly positively correlated with CRBN expression in some cancer types including lung adenocarcinoma (LUAD), kidney renal clear cell carcinoma (KIRC), and skin cutaneous melanoma (SKCM). CRBN expression was downregulated regardless of clinicopathological characteristics in LUAD and KIRC. Analysis of genes that are commonly correlated with CRBN expression among KIRC, LUAD, and SKCM samples elucidated the potential CRBN-associated mechanisms of cancer progression. Overall, this study revealed the prognostic value of CRBN and its potential associated mechanisms, which may facilitate the development of anti-cancer therapeutic agents.