研究 PPT2 在卵巢癌预后和免疫治疗结果中的作用。
Investigating PPT2's role in ovarian cancer prognosis and immunotherapy outcomes.
发表日期:2024 Oct 11
作者:
Hui Xu, Yan Zhang, Zhen Xie, Xiao-Feng Xie, Wen-Lan Qiao, Miao Wang, Bei-Bei Zhao, Tian Hua
来源:
Journal of Ovarian Research
摘要:
卵巢癌(OC)仍然是妇科恶性肿瘤死亡的主要原因,并且尚未确定可靠的分子生物标志物来预测 OC 的结果。棕榈酰蛋白硫酯酶 2 (PPT2) 基因与代谢密切相关,但在 OC 中研究较少。本研究旨在确定 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谱 (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,然后进行 Kaplan-Meier 分析、单变量 Cox 回归、多变量 Cox 回归、列线图,并进行校准来评估和验证PPT2的作用。基因集富集分析(GSEA)用于找出与PPT2密切相关的通路。进行过表达实验来探讨PPT2的功能。我们的研究结果表明,在 TCGA、GTEx 数据集和 GEO 数据集中,与正常卵巢组织相比,OC 组织中 PPT2 mRNA 表达明显下调。这种差异表达也在我们的内部数据集中在 mRNA 和蛋白质水平上得到了证实。在 TCGA、几个 GEO 数据集和我们的内部数据集中,PPT2 表达的减少与较低的存活率相关。多变量分析显示,在 TCGA 和 GEO 中,PPT2 是预测 OC 患者更好结果的独立因素。通过单样本 GSEA (ssGSEA) 揭示免疫浸润与 PPT2 表达之间存在负相关。此外,PPT2 与上调的免疫评分、基质评分和估计评分呈负相关,这表明 PPT2 表达低的患者可能从免疫治疗中受益更多。许多化学药物在 PPT2 高表达的患者中显示出较低的 IC50。在对几个 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OC细胞增殖。我们的结果表明,PPT2 被认为是 OC 的有利预后生物标志物,并且对于预测免疫治疗和化疗的反应可能至关重要。需要进一步研究以充分了解 PPT2 与 OC 患者免疫治疗疗效之间的关系。© 2024。作者。
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.© 2024. The Author(s).