A newly defined basement membrane-related gene signature for the prognosis of clear-cell renal cell carcinoma

Abstract

Background: Basement membranes (BMs) are associated with cell polarity, differentiation, migration, and survival. Previous studies have shown that BMs play a key role in the progression of cancer, and thus could serve as potential targets for inhibiting the development of cancer. However, the association between basement membrane-related genes (BMRGs) and clear cell renal cell carcinoma (ccRCC) remains unclear. To address that gap, we constructed a novel risk signature utilizing BMRGs to explore the relationship between ccRCC and BMs. Methods:We gathered transcriptome and clinical data from The Cancer Genome Atlas (TCGA) and randomly separated the data into training and test sets to look for new potential biomarkers and create a predictive signature of BMRGs for ccRCC. We applied univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses to establish the model. The risk signature was further verified and evaluated through principal component analysis (PCA), the Kaplan-Meier technique, and time-dependent receiver operating characteristics (ROC). A nomogram was constructed to predict the overall survival (OS). The possible biological pathways were investigated through functional enrichment analysis. In this study, we also determined tumor mutation burden (TMB) and performed immunological analysis and immunotherapeutic drug analysis between the high-and low-risk groups.Results: We identified 33 differentially expressed genes and constructed a risk model of eight BMRGs, including COL4A4, FREM1, CSPG4, COL4A5, ITGB6, ADAMTS14, MMP17, and THBS4. The PCA analysis showed that the signature

Identification of clear cell renal cell carcinoma subtypes by integrating radiomics and transcriptomics

“…LOXL2 is overexpressed in RCC, and its silencing suppresses the migration and invasion of cancer cells in ccRCC cell lines [ 39 ]. FREM1 has been identified as an independent prognostic factor in ccRCC and is negatively correlated with tumor staging [ 40 , 41 ]. Although MUC16 exhibits a high mutation frequency in ccRCC, studies on its prognostic implications are limited [ 42 ].…”

Decoding tumor heterogeneity in uveal melanoma: basement membrane genes as novel biomarkers and therapeutic targets revealed by multi-omics approaches for cancer immunotherapy

“…Several recent studies have already attempted to mine public databases to identify prognostic gene signatures related to BM proteins in tumors. For example, Cai et al identified a 7-gene signature associated with basement membrane proteins that predicted the prognostic status of breast cancer patients and provided insights for immunotherapy ( Cai et al, 2022 ); Zhou et al developed a risk model using 8 BMRGs, which revealed that clear-cell renal cell carcinoma patients in the low-risk group had a better response to immunotherapy ( Zhou et al, 2022 ); Lin et al established a 7-BMRG signature and identified five small compounds that could potentially be used for the treatment of pancreatic cancer patients, providing new perspectives for a deeper understanding of this disease ( Lin et al, 2023 ). Overall, these studies highlight the significance of basement membrane proteins in the precise treatment of tumors.…”

Comprehensive analyses of immune tumor microenvironment in papillary renal cell carcinoma

“…It is highly associated with several immune cells in ccRCC, such as activated dendritic cell, central memory CD8 T cell, central memory CD4 T cell, and activated CD4 T cell. 61 Finally, the gene EPHA3, Eph receptor tyrosine kinases, formerly known as HEK, contribute to tumor development, modulating cell-cell adhesion and survival during invasion, neo-angiogenesis and metastasis. 62 Therefore, the gene EPHA3 represents a potential source of tumorspecific antigens recognized on tumor cells that express human leukocyte antigens (HLA) class II molecules.…”