Department of Gynecology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Xuzhou Medical University, Xuzhou, China.
PLoS One. 2023 Aug 15;18(8):e0290031. doi: 10.1371/journal.pone.0290031. eCollection 2023.
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.
长链非编码 RNA (LncRNA) PAXIP1 反义 RNA 1 (PAXIP1-AS1) 被发现可促进卵巢癌 (OC) 细胞系中 OC 细胞的增殖、迁移、EMT 和凋亡，但 PAXIP1-AS1 表达与 OC 患者临床特征、预后和免疫浸润的关系及其调控网络尚不清楚。从癌症基因组图谱 (TCGA) 数据库中收集了 379 份 OC 组织。从 GTEx 联合 TCGA 数据库中收集了 427 份 OC 组织和 88 份正常卵巢组织。从 GSE138866 中收集了 130 份 OC 样本。Kruskal-Wallis 检验、Wilcoxon 符号秩检验、逻辑回归、Kaplan-Meier 方法、Cox 回归分析、基因集富集分析 (GSEA) 和免疫浸润分析用于评估临床特征与 PAXIP1-AS1 表达、预后因素的关系，并确定 PAXIP1-AS1 在功能中的显著参与。实时定量 PCR 用于验证 OC 细胞系中 PAXIP1-AS1 的表达。OC 中低表达 PAXIP1-AS1 与年龄 (P = 0.045)、组织学分级 (P = 0.011) 和淋巴浸润 (P = 0.004) 有关。低 PAXIP1-AS1 表达预测总生存期 (OS) 较差 (HR: 0.71; 95% CI: 0.55-0.92; P = 0.009)、无进展间隔 (PFS) (HR: 1.776; 95% CI: 1.067-2.955; P = 0.001) 和疾病特异性生存期 (DSS) (HR: 0.67; 95% CI: 0.51-0.89; P = 0.006)。PAXIP1-AS1 表达 (HR: 0.711; 95% CI: 0.542-0.934; P = 0.014) 与 OC 患者的 PFS 独立相关。GSEA 表明，嗜中性粒细胞脱颗粒、白细胞介素信号、G 蛋白偶联受体配体结合、G 蛋白α I 信号事件、VEGFAVEGFR-2 信号通路、naba 分泌因子、A 类 1 视紫红质样受体、PI3K-Akt 信号通路和粘着斑-PI3K-Akt-mTOR 信号通路在 PAXIP1-AS1 高表达表型中差异富集。与 IOSE29 细胞系相比，OC 细胞系中 PAXIP1-AS1 明显下调。PAXIP1-AS1 的表达与免疫浸润有关。来自 GSE138866 的低表达 PAXIP1-AS1 与较差的 OS 相关 (HR: 0.52; 95% CI: 0.34-0.80; P = 0.003)。PAXIP1-AS1 高表达组和低表达组之间存在一些基因组变异。OC 中低表达 PAXIP1-AS1 与生存和免疫浸润不良显著相关。PAXIP1-AS1 可能是一种有前途的 OC 预后生物标志物和免疫治疗反应预测因子。
