M2‐polarization‐related CNTNAP1 gene might be a novel immunotherapeutic target and biomarker for clear cell renal cell carcinoma

Abstract

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies, characterized by high mortality rate in urology. Unfortunately, reliable biomarkers for ccRCC diagnosis and prognosis remain lacking. Contactin‐associated protein 1 (CNTNAP1) has yet to be thoroughly investigated in cancer, especially its relationship with immune infiltration or clinical outcomes of ccRCC. Here, we explored The Cancer Genome Atlas Kidney Clear Cell Carcinoma database (TCGA‐KIRC) for prognostic significance, differential expression, and probable mechanism of CNTNAP1. The aberrant CNTNAP1 expression was also validated by the International Cancer Genome Consortium (ICGC) and ccRCC clinic samples. We used Database for Annotation, Visualization, and Integrated Discovery to perform the GO and KEGG enrichment. TIMER database was further utilized to assess its correlation with immune infiltration in ccRCC. The CellMiner database was used to analyze the relationship between CNTNAP1 expression and drug sensitivity. Results showed CNTNAP1 was upregulated in TCGA‐KIRC, ICGC, and clinic samples. And CNTNAP1 expression was positively related to infiltration levels of cancer‐associated fibroblast, regulatory T cells, and myeloid‐derived suppressor cells, while negatively related to eosinophils. Furthermore, we observed CNTNAP1 was appreciably positively associated with alternatively activated macrophage (M2) in ccRCC. Finally, high CNTNAP1 expression was negatively correlated with nilotinib, crizotinib, eribulin mesylate, and vinorelbine. Collectively, these results strongly suggest that CNTNAP1 might act as an immunotherapeutic target and a promising novel biomarker for ccRCC.

Inflammatory response-based prognostication and personalized therapy decisions in clear cell renal cell cancer to aid precision oncology

“…Limited evidence has revealed the implications of a single gene from the IRscore in ccRCC. A bioinformatics study found that CNTNAP1 is up-regulated in ccRCC, and appreciably linked with poor clinical outcomes and immunological properties [ 52 ]. Two other bioinformatics studies demonstrated the prognostic relevance of COL7A1 and CRABP2 in ccRCC [ 53 , 54 ].…”

Tracking the Molecular Scenarios for Tumorigenic Remodeling of Extracellular Matrix Based on Gene Expression Profiling in Equine Skin Neoplasia Models

“…However, there are reports that this gene is related to clear-cell renal carcinoma. In this tumor, the expression of the CNTNAP1 gene was positively associated with cancer-associated fibroblasts [ 42 ]. The detection of the deregulated expression of this gene in sarcoid tissue samples, as compared to healthy skin-derived explants, may provide the empirical evidence and mechanistic insights that, despite its mainly neurological connections, the CNTNAP1 gene may be a valuable source of information on the molecular basis of sarcoid formation.…”