研究PPT2在卵巢癌预后和免疫疗法结果中的作用

卵巢癌（OC）仍然是妇科恶性肿瘤中死亡率的主要原因，并且鉴定可靠的分子生物标志物预测OC的结果尚未实现。在OC中稀疏研究的基因棕榈酰蛋白硫酯酶2（PPT2）与代谢密切相关。这项研究旨在确定OC中PPT2表达，预后，免疫浸润和潜在分子机制之间的关联。我们从癌症基因组图集（TCGA），基因型 - 组织表达（GTEX）和基因表达综合（GEO）数据库中获得了RNA-SEQ和临床数据，然后是Kaplan-Meier分析，Univariate Cox Recressions，Multivariate Cox Recression，Multivariate Cox回归，提名，提名，提名，校准，评估和校准，并评估PCT22。基因集富集分析（GSEA）用于找出与PPT2紧密相关的途径。进行过表达实验以探索PPT2的功能。我们的发现表明，与TCGA，GTEX数据集和GEO数据集中的正常卵巢组织相比，OC组织中的PPT2 mRNA表达明显是下调。在我们的内部数据集中，在mRNA和蛋白质水平上都证实了这种差异表达。 PPT2表达的降低与TCGA，几个GEO数据集和我们内部数据集的生存率降低相关。多变量分析表明，PPT2是预测TCGA和GEO中OC患者更好结果的独立因素。通过单样本GSEA（SSGSEA），免疫浸润和PPT2表达之间揭示了负相关。此外，PPT2与上调的免疫评分，基质评分和估计评分负相关，这表明PPT2表达低的患者可能受益于免疫疗法。在高PPT2表达的患者中，许多化学剂显示出较低的IC50。在几个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，我们发现PPT2在体外抑制了OC细胞的增殖。我们的结果表明，PPT2被认为是OC的有利的预后生物标志物，对于预测对免疫疗法和化学疗法的反应可能至关重要。需要进一步的研究以充分了解OC患者的PPT2与免疫疗法功效之间的关系。

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.