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PAXIP1-AS1与卵巢癌的免疫浸润相关,并预测着预后不良。

PAXIP1-AS1 is associated with immune infiltration and predicts poor prognosis in ovarian cancer.

发表日期:2023
作者: Buze Chen, Xiaoyuan Lu, Qingmei Zhou, Qing Chen, Siyan Zhu, Guilin Li, Hui Liu
来源: Immunity & Ageing

摘要:

长非编码RNA(LncRNA)PAXIP1反义RNA1(PAXIP1-AS1)在卵巢癌(OC)细胞中促进增殖、迁移、EMT和凋亡。但PAXIP1-AS1表达与OC患者的临床特征、预后、免疫浸润以及其调控网络的关系尚不清楚。从癌症基因组图谱(TCGA)数据库中收集了379个OC组织。从GTEX与TCGA结合的数据库中收集了427个OC组织和88个正常卵巢组织。从GSE138866中收集了130个OC样本。采用Kruskal-Wallis检验、威尔科克森符号秩检验、逻辑回归、Kaplan-Meier法、Cox回归分析、基因集富集分析(GSEA)和免疫浸润分析评估临床特征与PAXIP1-AS1表达之间的关系、预后因素,并确定PAXIP1-AS1在功能中的重要作用。利用qRT-PCR验证了OC细胞系中PAXIP1-AS1的表达。 OC中低PAXIP1-AS1表达与年龄(P = 0.045)、组织级别(P = 0.011)和淋巴侵袭(P = 0.004)有关。低PAXIP1-AS1表达预示着较差的总生存(HR:0.71;95%CI:0.55-0.92;P = 0.009)、无病进展生存时间(PFS)(HR:1.776;95% CI:1.067-2.955;P = 0.001)和疾病特定生存(DSS)(HR:0.67;95%CI:0.51-0.89;P = 0.006)。 PAXIP1-AS1表达与OC患者的PFS独立相关(HR:0.711;95%CI:0.542-0.934;P = 0.014)。GSEA显示与PAXIP1-AS1高表达表型显著富集的差异包括中性粒细胞去颗粒化、白细胞介素信号通路、GPCR配体结合、G alpha I信号事件、VEGFA-VEGFR-2信号通路、naba分泌因子、A 1类类似视紫红功能受体、PI3K-Akt信号通路和聚焦性粘附-PI3K-Akt-mTOR信号通路。与IOSE29细胞株相比,PAXIP1-AS1在OC细胞株中显着下调。 PAXIP1-AS1的表达与免疫浸润有关。 GSE138866结果显示PAXIP1-AS1低表达与较差的总生存(HR:0.52; 95%CI:0.34-0.80;P = 0.003)相关。 PAXIP1-AS1高表达组与低表达组之间存在一些基因组变异。PAXIP1-AS1低表达与OC的较差生存和免疫浸润显著相关。对于OC,PAXIP1-AS1可能成为有希望的预后生物标志物和免疫治疗的响应指标。 版权: © 2023 Chen等。这是一篇根据Creative Commons Attribution License的开放获取文章,允许在任何媒介下自由使用、分发和复制,只要保持原始作者和来源的署名不变。
The long non-coding RNA (LncRNA) PAXIP1 antisense RNA 1 (PAXIP1-AS1) was found to promote proliferation, migration, EMT, and apoptosis of ovarian cancer (OC) cells in OC cell lines, but the relationship between PAXIP1-AS1 expression and clinical characteristics, prognosis, and immune infiltration of OC patients and its regulatory network are unclear. 379 OC tissues were collected from The Cancer Genome Atlas (TCGA) database. 427 OC tissues and 88 normal ovarian tissues were collected from GTEx combined TCGA database. 130 OC samples were collected from GSE138866. Kruskal-Wallis test, Wilcoxon sign-rank test, logistic regression, Kaplan-Meier method, Cox regression analysis, Gene set enrichment analysis (GSEA), and immuno-infiltration analysis were used to evaluate the relationship between clinical characteristics and PAXIP1-AS1 expression, prognostic factors, and determine the significant involvement of PAXIP1-AS1 in function. QRT-PCR was used to validate the expression of PAXIP1-AS1 in OC cell lines. Low PAXIP1-AS1 expression in OC was associated with age (P = 0.045), histological grade (P = 0.011), and lymphatic invasion (P = 0.004). Low PAXIP1-AS1 expression predicted a poorer overall survival (OS) (HR: 0.71; 95% CI: 0.55-0.92; P = 0.009), progression free interval (PFS) (HR: 1.776; 95% CI: 1.067-2.955; P = 0.001) and disease specific survival (DSS) (HR: 0.67; 95% CI: 0.51-0.89; P = 0.006). PAXIP1-AS1 expression (HR: 0.711; 95% CI: 0.542-0.934; P = 0.014) was independently correlated with PFS in OC patients. GSEA demonstrated that neutrophil degranulation, signaling by Interleukins, GPCR-ligand binding, G alpha I signaling events, VEGFAVEGFR-2 signaling pathway, naba secreted factors, Class A 1 Rhodopsin-Like Receptors, PI3K-Akt signaling pathway, and Focal Adhesion-PI3K-Akt-mTOR-signaling pathway were differentially enriched in PAXIP1-AS1 high expression phenotype. PAXIP1-AS1 was significantly downregulated in OC cell lines compared with IOSE29 cell line. The expression of PAXIP1-AS1 was associated with immune infiltration. low expression of PAXIP1-AS1 was correlated with poor OS (HR: 0.52; 95% CI: 0.34-0.80; P = 0.003) from GSE138866. There were some genomic variations between the PAXIP1-AS1 high and low expression groups. Low expression of PAXIP1-AS1 was significantly associated with poor survival and immune infiltration in OC. PAXIP1-AS1 could be a promising prognosis biomarker and response to immunotherapy for OC.Copyright: © 2023 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.