Background. The present study is aimed at evaluating the functional and clinical values of P3H4 in lung adenocarcinoma. Moreover, we also investigated the downstream pathways that P3H4 might participate in. Methods. The differential expression analysis was used to identify genes differentially expressed in lung adenocarcinoma tissues as compared with normal tissues. Survival analysis was used to test the association between P3H4 and survival time. Gene set enrichment analysis was conducted to explore the downstream pathways. CCK8 and transwell were employed to examine the impact of P3H4 on cell phenotypes. Results. P3H4 was highly upregulated in LUAD tissues at both RNA and protein levels. Moreover, the LUAD patients, who had high expression of P3H4, were also observed to have shorter disease-free survival and overall survival. These results demonstrated that P3H4 could be used as a prognostic biomarker for LUAD. Moreover, we also found that it was the copy number alterations (CNAs), not DNA methylation, that regulated the RNA expression of P3H4, indicating that its upregulation might be partially resulted from the CNAs. Furthermore, functional experiments revealed that the A549 and H1299 cells with siRNA treatment (siP3H4) exhibited significantly decreased cell proliferation after 24 hours, migratory ability, and invasiveness. Functionally, the upregulated proteins in the P3H4 high expression group were mainly enriched in tumor microenvironment-related pathways such as phagosome, focal adhesion, and ECM-receptor interaction and cancer-related pathways such as bladder cancer pathway, proteoglycans in cancer, and hippo signaling pathway. Conclusion. The present study systematically evaluated the functional and clinical values of P3H4 in LUAD, and explored the related biological pathways. P3H4 might promote LUAD progression through regulating tumor microenvironment-related pathways.

中文翻译：

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P3H4 过表达作为肺腺癌的预后因素

背景。本研究旨在评估 P3H4 在肺腺癌中的功能和临床价值。此外，我们还研究了 P3H4 可能参与的下游途径。方法。差异表达分析用于鉴定与正常组织相比在肺腺癌组织中差异表达的基因。生存分析用于测试 P3H4 与生存时间之间的关联。进行基因集富集分析以探索下游途径。CCK8 和transwell 用于检查P3H4 对细胞表型的影响。结果. P3H4 在 LUAD 组织中在 RNA 和蛋白质水平上都高度上调。此外，还观察到 P3H4 高表达的 LUAD 患者的无病生存期和总生存期较短。这些结果表明 P3H4 可用作 LUAD 的预后生物标志物。此外，我们还发现调节 P3H4 的 RNA 表达的是拷贝数改变 (CNA)，而不是 DNA 甲基化，表明其上调可能部分由 CNA 引起。此外，功能实验表明，经 siRNA 处理 (siP3H4) 的 A549 和 H1299 细胞在 24 小时后表现出显着降低的细胞增殖、迁移能力和侵袭性。在功能上，结论。本研究系统评价了 P3H4 在 LUAD 中的功能和临床价值，并探索了相关的生物学途径。P3H4 可能通过调节肿瘤微环境相关通路促进 LUAD 进展。