Zhang Yanna, Du Ting, Chen Xiancheng
State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Noncoding RNA and Drug Discovery Key Laboratory of Sichuan Province, Chengdu Medical College, Chengdu, China.
Front Oncol. 2022 Feb 8;12:818977. doi: 10.3389/fonc.2022.818977. eCollection 2022.
Although the effect of pseudogene ANXA2P2 on some tumors has been reported in a few literatures, the therapeutic potential and prognostic value of ANXA2P2 in ovarian serous cystadenocarcinoma (OV) have not been elucidated.
The correlation for ANXA2P2 expression patterns to prognostic characteristics, tumor immune microenvironment, immune cell infiltration level, tumor mutation burden (TMB), tumor microsatellite instability (MSI), drug sensitivity, and pathway function enrichment were investigated in pan-carcinoma TCGA and GTEx databases. Subsequently, the role of ANXA2P2 expression levels in the pathway enrichments and prognosis prediction in OV were further explored using weighted correlation network analysis (WGCNA) analysis, gene mutation analysis, and risk-independent prognostic analysis.
ANXA2P2 was frequently overexpressed in a variety of tumors compared with normal tissues. The correlation analysis for prognostic characteristics, tumor immune microenvironment, immune cell infiltration level, TMB, MSI, drug sensitivity, and pathway function enrichment revealed that ANXA2P2 expression patterns might deal a significant impact on the pathogenesis, development, and prognosis of various tumors. Then, GSVA, GSEA, WGCNA, gene mutation, and independent prognostic analysis for OV have indicated that high expression in ANXA2P2 could be mostly enriched in TNF-α signaling--NF-κB, epithelial-mesenchymal transition, apical junction, IL-6-JAK STAT3 signaling, etc., which were also proved to act as crucial factors on tumorigenesis, development, invasion, and metastasis. The mutation of TP53 (94%), TTN (24%), and CSMD3 (9%) in the biological process of tumor had been confirmed by relevant studies. Finally, the independent prognostic analysis demonstrated that ANXA2P2 expression in OV contributes greatly to the dependability of 3- and 5-year survival prediction.
In summary, our findings might provide a helpful foundation for prospective explorative researches, afford new strategies for the clinical treatment, deal prognosis prediction, and give new hope for OV patients.
尽管已有少数文献报道了假基因ANXA2P2对某些肿瘤的影响，但ANXA2P2在卵巢浆液性囊腺癌（OV）中的治疗潜力和预后价值尚未阐明。
在泛癌TCGA和GTEx数据库中研究ANXA2P2表达模式与预后特征、肿瘤免疫微环境、免疫细胞浸润水平、肿瘤突变负担（TMB）、肿瘤微卫星不稳定性（MSI）、药物敏感性和通路功能富集之间的相关性。随后，使用加权基因共表达网络分析（WGCNA）、基因突变分析和风险独立预后分析进一步探讨ANXA2P2表达水平在OV通路富集和预后预测中的作用。
与正常组织相比，ANXA2P2在多种肿瘤中经常过度表达。对预后特征、肿瘤免疫微环境、免疫细胞浸润水平、TMB、MSI、药物敏感性和通路功能富集的相关性分析表明，ANXA2P2表达模式可能对各种肿瘤的发病机制、发展和预后产生重大影响。然后，对OV的基因集变异分析（GSVA）、基因集富集分析（GSEA）、WGCNA、基因突变和独立预后分析表明，ANXA2P2的高表达主要富集在TNF-α信号通路-NF-κB、上皮-间质转化、顶端连接、IL-6-JAK STAT3信号通路等中，这些也被证明是肿瘤发生、发展、侵袭和转移的关键因素。相关研究已证实肿瘤生物学过程中TP53（94%）、TTN（24%）和CSMD3（9%）的突变。最后，独立预后分析表明，OV中ANXA2P2的表达对3年和5年生存预测的可靠性有很大贡献。
总之，我们的研究结果可能为前瞻性探索性研究提供有益的基础，为临床治疗提供新策略，进行预后预测，并为OV患者带来新希望。
