CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：GPD1L as a potential biomarker associated with Treg cell infiltration and lipid metabolism in clear cell renal cell carcinoma.
GPD1L as a potential biomarker associated with Treg cell infiltration and lipid metabolism in clear cell renal cell carcinoma.
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我们的结果支持 GPD1L 可能是一个有价值的生物标志物，用于预测和干预 ccRCC 进展。这些见解可能有助于揭示肿瘤细胞适应性生存与 Treg 浸润之间复杂的相互作用，这反映了 GPD1L 在 ccRCC 中的全面和系统性作用。
透明细胞肾细胞癌（ccRCC）是泌尿系统中常见的肿瘤，预后较差，但伴有高度免疫浸润。了解这种异常浸润的机制并确定相关的预后生物标志物对于改善治疗结果至关重要。
采用公共数据库（TCGA）分析GPD1L在ccRCC中的表达。通过western blotting、real time qPCR和免疫组化验证GPD1L在ccRCC细胞系和组织样本中的表达。通过生存分析、ROC曲线和Cox回归分析评估GPD1L的预测价值。我们使用GO、KEGG和基因集富集分析（GSEA）相互验证。然后进一步分析并验证单细胞测序数据集（GEO），并通过功能实验探索GPD1L在ccRCC中的功能表型。此外，基于癌症药物敏感性基因组学数据库数据库（GDSC）分析GPD1L表达水平与AKT-mTOR通路耐药之间的相关性。
我们确定甘油-3-磷酸脱氢酶1样蛋白（GPD1L）为ccRCC中的抑癌基因，GPD1L的下调可能通过增强调节性T细胞（Tregs）浸润和ccRCC中的脂质代谢重编程促进肿瘤细胞的适应性生存。我们的结果表明，在生存概率较差的ccRCC患者中，GPD1L显著减少。在机制上，GPD1L表达与Tregs浸润之间存在显著的负相关，GPD1L相关的代谢分析反映了Tregs与脂质代谢之间的相关性。此外，GPD1L表达水平还影响ccRCC的恶性表型以及对AKT和mTOR靶向治疗的耐药性。
Clear cell renal cell carcinoma (ccRCC) is a prevalent tumor in the urinary system, presenting a poor prognosis yet being accompanied by a high degree of immune infiltration. Understanding the mechanisms underlying this abnormal infiltration and identifying prognostic biomarkers in this regard is crucial for improving therapeutic outcomes.
The expression of GPD1L in ccRCC was analyzed using a common database (TCGA). The expression of GPD1L in ccRCC cell lines and tissue samples was verified by western blotting, real time qPCR and immunohistochemistry. The predictive value of GPD1L was evaluated by survival analysis, ROC curve and Cox regression analysis. We used GO, KEGG and gene set enrichment analysis (GSEA) to verify each other. Then the single cell sequencing dataset (GEO) was further analyzed and verified, and the functional phenotype of GPD1L in ccRCC was explored by functional experiments. In addition, the correlation between the expression level of GPD1L and drug resistance of AKT-mTOR pathway was analyzed based on Genomics of Drug Sensitivity in Cancer database (GDSC).
We identified glycerol-3-phosphate dehydrogenase 1-like (GPD1L) as a tumor suppressor gene in ccRCC, and downregulation of GPD1L may facilitate the adaptive survival of tumor cells via enhanced regulatory T cells (Tregs) infiltration and lipid metabolism reprogramming in ccRCC. Our results suggest that there is a significantly diminished GPD1L in ccRCC patients with poorer survival probability. Mechanically, a significant negative correlation between GPD1L expression and Tregs infiltration, and GPD1L-related metabolic analysis reflected the correlation between Tregs and lipid metabolism. In addition, GPD1L expression levels also influence the malignant phenotype of ccRCC and the drug resistance to AKT and mTOR targeted therapy.
Taken together, our results supported GPD1L could be a valuable biomarker for predicting and intervening in ccRCC progression. These insights could shed light on the complex interplay between tumor cell adaptive survival and Treg infiltration, which reflected that the comprehensive and systemic role of GPD1L in ccRCC.
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