Establishment of a Seven-Gene Signature Associated with CD8+ T Cells through the Utilization of Both Single-Cell and Bulk RNA-Sequencing Techniques in Clear Cell Renal Cell Carcinoma

Abstract

Tumor immune microenvironment constituents, such as CD8+ T cells, have emerged as crucial focal points for cancer immunotherapy. Given the absence of reliable biomarkers for clear cell renal cell carcinoma (ccRCC), we aimed to ascertain a molecular signature that could potentially be linked to CD8+ T cells. The differentially expressed genes (DEGs) linked to CD8+ T cells were identified through an analysis of single-cell RNA sequencing (scRNA-seq) data obtained from the Gene Expression Omnibus (GEO) database. Subsequently, immune-associated genes were obtained from the InnateDB and ImmPort datasets and were cross-referenced with CD8+ T-cell-associated DEGs to generate a series of DEGs linked to immune response and CD8+ T cells. Patients with ccRCC from the Cancer Genome Atlas (TCGA) were randomly allocated into testing and training groups. A gene signature was established by conducting LASSO-Cox analysis and subsequently confirmed using both the testing and complete groups. The efficacy of this signature in evaluating immunotherapy response was assessed on the IMvigor210 cohort. Finally, we employed various techniques, including CIBERSORT, ESTIMATE, ssGSEA, and qRT-PCR, to examine the immunological characteristics, drug responses, and expression of the signature genes in ccRCC. Our findings revealed 206 DEGs linked to immune response and CD8+ T cells, among which 65 genes were correlated with overall survival (OS) in ccRCC. A risk assessment was created utilizing a set of seven genes: RARRES2, SOCS3, TNFSF14, XCL1, GRN, CLDN4, and RBP7. The group with a lower risk showed increased expression of CD274 (PD-L1), suggesting a more favorable response to anti-PD-L1 treatment. The seven-gene signature demonstrated accurate prognostic prediction for ccRCC and holds potential as a clinical reference for treatment decisions.

Identification of CNKSR1 as a biomarker for “cold” tumor microenvironment in lung adenocarcinoma: An integrative analysis based on a novel workflow

“…We observed a decrease in CD8 + T-cell infiltration in the high-CNKSR1 group, indicating that CNKSR1-mediated immune escape mechanisms may hold promise for the treatment of “cold” tumors. While extensive research has been conducted to identify potential immunotherapy biomarkers in cancers, many of the discoveries involve gene signatures composed of multiple molecules, and the expression levels of the signatures were parallel to that of PD-L1 [ 47 , 48 ]. In contrast, we believe that the identification of a specific immune-related gene that is mutually exclusive with PD-L1 holds greater significance for future research and application.…”