Department of Breast Surgery, Zhujiang Hospital, Southern Medical University, Guangdong, China.
Department of Thoracic Surgery, Zhujiang Hospital, Southern Medical University, Guangdong, China.
PLoS Comput Biol. 2024 Nov 6;20(11):e1012284. doi: 10.1371/journal.pcbi.1012284. eCollection 2024 Nov.
Prolyl-4-hydroxylase subunit alpha3 (P4HA3) is a triple helical procollagen synthesis protein. The role of P4HA3 in cancer development is not well known and lacks comprehensive analyses among human cancers. This study aimed to investigate the relationship between P4HA3 expression and anti-tumor immunity and its prognostic value in pan-cancer. P4HA3 expression was analyzed from TIMER2.0, GTEx, GEPIA2.0 and TCGA databases. Genetic and DNA methylation alterations, survival analysis and proteins co-expression analysis of P4HA3 in cBio Cancer Genomics Portal, TCGA, GSCA and TIMER2.0. The correlation between P4HA3 expression and immune infiltration was analyzed by TIDE, XCELL, MCPCOUNTER, and EPIC. We performed EdU and transwell experiments to evaluate the influence of P4HA3 on the proliferation, migration and invasion abilities of different tumors. Patients derived xenograft (PDX) and subcutaneous transplantation models were utilized to explore the correlation between P4HA3 and immunotherapy response in triple-negative breast cancer (TNBC). Among 33 types of cancers, P4HA3 had generally different expression between different tumors, further analysis showed that the expression of P4HA3 was correlated with the cells infiltration of the tumor microenvironment (TME). The expression of P4HA3 was positively with the cell proliferation markers and epithelial-mesenchymal transition (EMT) markers. Moreover, P4HA3 deficiency inhibited the proliferation, migration and invasion abilities of tumor cells, and promoted anti-tumor immunotherapy of PD-1/PD-L1 inhibitor. This pan-cancer analysis of P4HA3 provides a comprehensive understanding of its oncogenic and prognosis role in different cancers, P4HA3 abnormal expression could be a useful biomarker for predicting the effectiveness of immunotherapy in cancer patients.
脯氨酰-4-羟化酶亚基α3（P4HA3）是一种三螺旋原胶原合成蛋白。P4HA3 在癌症发展中的作用尚不清楚，并且在人类癌症中缺乏全面的分析。本研究旨在探讨 P4HA3 表达与抗肿瘤免疫的关系及其在泛癌中的预后价值。从 TIMER2.0、GTEx、GEPIA2.0 和 TCGA 数据库中分析 P4HA3 的表达。在 cBio Cancer Genomics Portal、TCGA、GSCA 和 TIMER2.0 中分析 P4HA3 的遗传和 DNA 甲基化改变、生存分析和蛋白质共表达分析。通过 TIDE、XCELL、MCPCOUNTER 和 EPIC 分析 P4HA3 表达与免疫浸润的相关性。我们进行 EdU 和 Transwell 实验，以评估 P4HA3 对不同肿瘤增殖、迁移和侵袭能力的影响。利用患者来源的异种移植（PDX）和皮下移植模型探讨 P4HA3 与三阴性乳腺癌（TNBC）免疫治疗反应的相关性。在 33 种癌症中，P4HA3 在不同肿瘤之间的表达普遍不同，进一步分析表明，P4HA3 的表达与肿瘤微环境（TME）中细胞浸润有关。P4HA3 的表达与细胞增殖标志物和上皮-间充质转化（EMT）标志物呈正相关。此外，P4HA3 缺失抑制肿瘤细胞的增殖、迁移和侵袭能力，并促进 PD-1/PD-L1 抑制剂的抗肿瘤免疫治疗。这项对 P4HA3 的泛癌分析提供了对其在不同癌症中的致癌和预后作用的全面理解，P4HA3 异常表达可能是预测癌症患者免疫治疗效果的有用生物标志物。
