LINC00941 Promotes Cell Malignant Behavior and Is One of Five Costimulatory Molecule-Related lncRNAs That Predict Prognosis in Renal Clear Cell Carcinoma.

Background and Objectives: A significant role was played by costimulatory molecules in renal cancer. However, the lncRNAs regulating costimulatory molecules have not been fully investigated. Materials and Methods: Data from the next-sequence file and clinical data were downloaded from the Cancer Genome Atlas (TCGA) database. All analyses were conducted using the R and GraphPad Prism software. Results: A total of 1736 costimulatory molecule-related lncRNAs were determined under the threshold of |Cor| > 0.5 and p-value < 0.001. Furthermore, a prognosis prediction signature consisting of five lncRNAs: LINC00941, AC016773.1, AL162171.1, HOTAIRM1, and AL109741.1 was established with great prediction ability. By combining risk score and clinical parameters, a nomogram plot was constructed for better clinical practice. A biological enrichment analysis indicated that E2F targets, coagulation, IL6/JAK/STAT3 signaling, G2/M checkpoint, and allograft rejection pathways were activated in high-risk patients. Furthermore, a higher infiltration level of resting CD4+ T cell, M2 macrophage, and resting mast cells, while a lower CD8+ T cell infiltration was observed in high-risk patients. It is worthy of note that, low-risk patients might respond better to PD-1 checkpoint therapy. A correlation analysis of LINC00941 revealed that it was positively correlated with Th2 cells, Th1 cells, macrophages, and Treg cells, but negatively correlated with Th17 cells. A pathway enrichment analysis indicated that the pathways of the inflammatory response, G2M checkpoint, and IL6/JAK/STAT3 signaling were significantly activated in patients with high LINC00941 expression. In vitro experiments indicated that LINC00941 can enhance the malignant biological behaviors of renal cancer cells. Conclusions: Our study established a costimulatory molecule-related lncRNAs-based prognosis model with a great prediction prognosis. In addition, LINC00941 could enhance the malignant biological behaviors of renal cancer cells.

Integrated Analysis of the Role of Enolase 2 in Clear Cell Renal Cell Carcinoma.

Enolase 2 (ENO2) has increasingly been documented in multiple cancers in recent years. However, the role of ENO2 in clear cell renal carcinoma (ccRCC) has not been fully explored. In the present study, open-access data were downloaded from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and the Human Protein Atlas (HPA) databases. All statistical analyses were performed in R and GraphPad Prism 8 softwares. Results showed that ENO2 was overexpressed in ccRCC tissues and cell lines and correlated with worse clinical features and prognosis. In vitro experiments indicated that the inhibition of ENO2 could hamper the malignant behaviors of ccRCC cells. Gene Set Enrichment Analysis showed that epithelial-mesenchymal transition, KRAS signaling, inflammatory response, angiogenesis, hypoxia, and WNT/ß-catenin pathways were upregulated in the ENO2 high-expression group; whereas adipogenesis, DNA repair, and androgen response pathways were downregulated. Immune infiltration analysis indicated that patients with high ENO2 levels might have higher M2 macrophages and lower Î³ß T cells in the tumor microenvironment, which may account to some extent for the worse prognosis of ENO2. Moreover, it was found that patients with low and high ENO2 expression might be more sensitive to PD-1 therapy and CTLA-4 therapy, respectively. In addition, patients with high ENO2 expression showed lower sensitivity to common chemotherapy drugs for ccRCC, including axitinib, cisplatin, gemcitabine, pazopanib, sunitinib, and temsirolimus. Overall, these results suggest that ENO2 is a potential prognosis biomarker of ccRCC and could affect the malignant biological behavior of cancer cells, highlighting its value as a potential therapeutic target.