研究PPT2在卵巢癌预后与免疫治疗效果中的作用

卵巢癌（OC）仍然是妇科恶性肿瘤中死亡率的首要原因，尚未找到可靠的分子生物标志物以预测OC的预后。脂肪酰蛋白硫酯酶2（PPT2）这一基因在OC中的研究较少，与代谢密切相关。本研究旨在探讨PPT2表达水平、预后、免疫浸润及潜在分子机制之间的关系。我们从癌症基因组图谱（TCGA）、基因型组织表达（GTEx）以及基因表达谱数据库（GEO）获取RNA测序数据和临床资料，然后通过Kaplan-Meier分析、单因素Cox回归、多因素Cox回归、列线图及校准曲线等方法评估并验证PPT2的作用。基因集富集分析（GSEA）被用来识别与PPT2密切相关的通路。过表达实验用于探索PPT2的功能。结果显示，在TCGA、GTEx及GEO数据集中，PPT2 mRNA在卵巢癌组织中明显低表达，且在我们的内源性样本中，PPT2的mRNA及蛋白水平也表现出差异表达。PPT2表达下降与TCGA、若干GEO数据集及我方样本中的较低生存率相关。多变量分析表明，PPT2在预测OC患者预后方面是一个独立的预后因素。在单样本GSEA（ssGSEA）分析中发现免疫浸润与PPT2表达呈负相关。此外，PPT2与免疫评分、基质评分和估算评分呈负相关，提示低PPT2表达的患者可能更适合免疫治疗。多种化学药物在高PPT2表达患者中显示出较低的半数抑制浓度（IC50）。在多个OC数据集的单细胞RNA测序（scRNA-seq）分析中，我们发现PPT2主要在内皮细胞中表达。此外，我们还发现PPT2在体外抑制卵巢癌细胞的增殖。我们的研究结果表明，PPT2被认为是卵巢癌的有利预后生物标志物，可能在预测免疫疗法和化疗反应中发挥重要作用。未来仍需进一步研究以全面理解PPT2与免疫治疗效果之间的关系。

Ovarian cancer (OC) remains the primary cause of mortality among gynecological malignancies, and the identification of reliable molecular biomarkers to prognosticate OC outcomes is yet to be achieved. The gene palmitoyl protein thioesterase 2 (PPT2), which has been sparsely studied in OC, was closely associated with metabolism. This study aimed to determine the association between PPT2 expression, prognosis, immune infiltration, and potential molecular mechanisms in OC. We obtained the RNA-seq and clinical data from The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx) and Gene Expression Omnibus (GEO) databases, then Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, nomogram, and calibration were conducted to assess and verify the role of PPT2. Gene set enrichment analysis (GSEA) was used to figure out the closely correlated pathways with PPT2. Overexpression experiment was performed to explore the function of PPT2. Our findings showed that PPT2 mRNA expression was apparent down-regulation in OC tissue compared to normal ovarian tissues in TCGA, GTEx datasets, and GEO datasets. This differential expression was also confirmed in our in-house datasets at both the mRNA and protein levels. Decreased PPT2 expression correlated with lower survival rates in TCGA, several GEO datasets, and our in-house datasets. Multivariate analysis revealed that PPT2 was an independent factor in predicting better outcomes for OC patients in TCGA and GEO. A negative correlation was revealed between immune infiltration and PPT2 expression through Single-sample GSEA (ssGSEA). Additionally, PPT2 was negatively correlated with an up-regulated immune score, stromal score, and estimate score, suggesting that patients with low PPT2 expression might benefit more from immunotherapy. Numerous chemical agents showed lower IC50 in patients with high PPT2 expression. In single-cell RNA sequencing (scRNA-seq) analysis of several OC datasets, we found PPT2 was mainly expressed in endothelial cells. Furthermore, we found that PPT2 inhibited OC cell proliferation in vitro. Our results demonstrated that PPT2 was considered a favorable prognostic biomarker for OC and may be vital in predicting response to immunotherapy and chemotherapy. Further research was needed to fully understand the relationship between PPT2 and immunotherapy efficacy in OC patients.