Abstract
Objective Clear cell renal cell carcinoma (ccRCC) carries significant morbidity and mortality globally and is often resistant to conventional radiotherapy and chemotherapy. Immune checkpoint blockade (ICB) has received attention in ccRCC patients as a promising anticancer treatment. Furthermore, competitive endogenous RNA (ceRNA) networks are crucial for the occurrence and progression of various tumors. This study was aimed at identifying reliable prognostic signatures and exploring potential mechanisms between ceRNA regulation and immune cell infiltration in ccRCC patients. Methods and Results Gene expression profiling and clinical information of ccRCC samples were obtained from The Cancer Genome Atlas (TCGA) database. Through comprehensive bioinformatic analyses, differentially expressed mRNAs (DEmRNAs; n = 131), lncRNAs (DElncRNAs; n = 12), and miRNAs (DEmiRNAs; n = 25) were identified to establish ceRNA networks. The CIBERSORT algorithm was applied to calculate the proportion of 22 types of tumor-infiltrating immune cells (TIICs) in ccRCC tissues. Subsequently, univariate Cox, Lasso, and multivariate Cox regression analyses were employed to construct ceRNA-related and TIIC-related prognostic signatures. In addition, we explored the relationship between the crucial genes and TIICs via coexpression analysis, which revealed that the interactions between MALAT1, miR-1271-5p, KIAA1324, and follicular helper T cells might be closely correlated with the progression of ccRCC. Ultimately, we preliminarily validated that the potential MALAT1/miR-1271-5p/KIAA1324 axis was consistent with the ceRNA theory by qRT-PCR in the ccRCC cell lines. Conclusion On the basis of the ceRNA networks and TIICs, we constructed two prognostic signatures with excellent predictive value and explored possible molecular regulatory mechanisms, which might contribute to the improvement of prognosis and individualized treatment for ccRCC patients.
Highlights
Renal cell carcinoma (RCC) is one of the most common malignancies of the urological system [1]
The results indicated that MALAT1 and KIAA1324 were highly expressed in Clear cell renal cell carcinoma (ccRCC) cell lines compared to a normal renal tubular epithelial cell line, while miR-1271-5p was lowly expressed (Figures 9(a), 9(b) and 9(c))
Emerging evidence suggests that tumor molecular profiles and the landscape of tumor-infiltrating immune cells (TIICs) play an essential role in tumor development, and they have been proposed as potential prognostic biomarkers [16, 17]
Summary
Renal cell carcinoma (RCC) is one of the most common malignancies of the urological system [1]. Clear cell renal cell carcinoma (ccRCC) is the most common type of malignant renal tumor with more malignant features and poor prognosis, accounting for most RCC-associated deaths [2]. CcRCC patients generally lack sensitivity to conventional chemotherapy and radiotherapy. Targeted therapies have made significant progress in improving the survival of patients with ccRCC, the median survival rate remains poor for high-grade and advanced-stage patients. To improve the prognosis of ccRCC patients, the exploration of novel mechanisms involved in ccRCC development and the identification of potential prognostic markers and therapeutic targets are urgently required. Salmena et al presented the competing endogenous RNA (ceRNA) hypothesis, whereby lncRNA is able to Disease Markers
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