• Huafeng Pan, Wei Wei, Guanghou Fu, Jiaren Pan, and Baiye Jin.
• Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
• Medicina (Kaunas). 2023 Jan 17; 59 (2).

AbstractBackground 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.

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