The incidence of renal clear cell carcinoma (ccRCC) is steadily growing, and cellular metastasis and extensive infiltration of CD8 T cells are the primary factors contributing to its undesirable prognosis. GLIPR2 (GLI pathogenesis related 2) belongs to the PR-1 family, and it was upregulated in hepatocellular carcinoma, playing a role in the regulation of epithelial cell to mesenchymal transition (EMT). However, its involvement in ccRCC remains unknown. Genes associated with tumor metastasis and CD8 T cell levels were identified through weighted gene coexpression network analysis (WGCNA) leveraging the TCGA and GEO databases. Afterwards we follow survival, univariate Cox regression, receiver operating characteristic (ROC) and drug susceptibility analyses confirmed the most influential gene. Further exploration of its molecular, metastatic, and immune properties was carried out through bioinformatics analysis and experimental validation. Initially, GLIPR2 was identified as the most influential gene via WGCNA. Our findings indicated that GLIPR2 exhibited high expression levels in ccRCC and metastatic ccRCC, and its over-expression is significantly correlated with an unfavorable prognosis. Competing endogenous RNAs (CeRNA) network analysis offered insights into the potential regulatory mechanisms governing its expression. Pathway enrichment analysis revealed the involvement of GLIPR2 in multiple pathways intertwined with immune and cellular metastasis. Meanwhile, experiments provided confirmation that GLIPR2 may facilitate the metastasis of ccRCC through EMT. However, the specific mechanisms by which GLIPR2 regulated EMT to promote invasion and migration in ccRCC required in-depth exploration. Single-cell sequencing, immune infiltration, immune survival, and immunotherapy analysis demonstrated the close association between GLIPR2 and CD8 T cells in ccRCC, as well as its potential for immunotherapeutic intervention. The upregulation of GLIPR2 in ccRCC is associated with cellular metastasis and enrichment of CD8 T cells. Herein, it may hold promising potential as a predictive independent biomarker for ccRCC metastasis, immune infiltration, and prognosis.

中文翻译：

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GLIPR2 成为肾透明细胞癌预后的潜在预测因子，与细胞转移和 CD8+ T 细胞浸润具有显着相关性


肾透明细胞癌（ccRCC）的发病率稳步增长，细胞转移和CD8 T细胞广泛浸润是导致其不良预后的主要因素。 GLIPR2（GLI发病机制相关2）属于PR-1家族，在肝细胞癌中表达上调，在上皮细胞向间质转化（EMT）的调节中发挥作用。然而，其参与 ccRCC 的情况仍不清楚。利用 TCGA 和 GEO 数据库，通过加权基因共表达网络分析 (WGCNA) 鉴定与肿瘤转移和 CD8 T 细胞水平相关的基因。随后，我们通过生存率、单变量 Cox 回归、接受者操作特征 (ROC) 和药物敏感性分析证实了最有影响力的基因。通过生物信息学分析和实验验证对其分子、转移和免疫特性进行了进一步探索。最初，GLIPR2 被 WGCNA 确定为最有影响力的基因。我们的研究结果表明，GLIPR2在ccRCC和转移性ccRCC中表现出高表达水平，其过度表达与不良预后显着相关。竞争性内源 RNA (CeRNA) 网络分析提供了对其表达的潜在调控机制的见解。通路富集分析揭示了 GLIPR2 参与与免疫和细胞转移交织在一起的多个通路。同时，实验证实GLIPR2可能通过EMT促进ccRCC转移。然而，GLIPR2调控EMT促进ccRCC侵袭和迁移的具体机制还需要深入探索。 单细胞测序、免疫浸润、免疫存活和免疫治疗分析证明了 ccRCC 中 GLIPR2 和 CD8 T 细胞之间的密切相关性及其免疫治疗干预的潜力。 ccRCC 中 GLIPR2 的上调与细胞转移和 CD8 T 细胞富集相关。在此，它作为 ccRCC 转移、免疫浸润和预后的独立预测生物标志物可能具有广阔的潜力。