Background: PERP, a member of the peripheral myelin protein gene family, is a new therapeutic target in cancer. The relationships between PERP and immune cell infiltration in lung cancer have not been studied. Therefore, the role of PERP in the tumour microenvironment (TME) of lung cancer needs to be further explored.
Methods: In this study, we explored the association between PERP expression and clinical characteristics by analysing data from the TCGA database. Cox regression and Kaplan‒Meier methods were used to investigate the relationship between the expression of PERP and overall survival in patients with lung adenocarcinoma (LUAD). The relationship between PERP expression and the degree of infiltration of specific immune cell subsets in LUAD was evaluated using the TIMER database and GEPIA. We also performed GO enrichment analysis and KEGG enrichment analysis to reveal genes coexpressed with PERP using the Coexpedia database. Finally, we verified the expression and function of PERP in LUAD tissues and the A549 cell line by RT‒PCR, Western blot, CCK-8, IHC, and wound healing assays. The mouse model was used to study the in vivo effects of PERP.
Results: According to our results, PERP expression was significantly higher in LUAD tissues and associated with the clinical characteristics of the disease. Survival was independently associated with PERP in LUAD patients. We further verified that PERP might regulate B-cell infiltration in LUAD to affect the prognosis of LUAD. To identify PERP-related signalling pathways in LUAD, we performed a genome-aggregation analysis (GSEA) between low and high PERP expression datasets. LUAD cells express higher levels of PERP than paracarcinoma cells, and PERP inhibits the proliferation and metastasis of A549 cells through apoptosis.
Conclusion: PERP may affect the prognosis of lung adenocarcinoma by inhibiting apoptosis and is associated with immune cell infiltration.



中文翻译：

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PERP可能通过抑制细胞凋亡影响肺腺癌的预后

背景： PERP是外周髓磷脂蛋白基因家族的成员，是癌症的新治疗靶点。PERP 与肺癌免疫细胞浸润之间的关系尚未研究。因此，PERP在肺癌肿瘤微环境（TME）中的作用有待进一步探讨。
方法：在本研究中，我们通过分析 TCGA 数据库的数据探讨了 PERP 表达与临床特征之间的关联。采用Cox回归和Kaplan-Meier法探讨肺腺癌（LUAD）患者PERP表达与总生存期的关系。使用TIMER数据库和GEPIA评估PERP表达与LUAD中特定免疫细胞亚群浸润程度之间的关系。我们还使用 Coexpedia 数据库进行了 GO 富集分析和 KEGG 富集分析，以揭示与 PERP 共表达的基因。最后，我们通过 RT-PCR、Western blot、CCK-8、IHC 和伤口愈合实验验证了 LUAD 组织和 A549 细胞系中 PERP 的表达和功能。使用小鼠模型来研究 PERP 的体内效应。
结果：根据我们的结果，PERP 表达在 LUAD 组织中显着较高，并且与该疾病的临床特征相关。LUAD 患者的生存率与 PERP 独立相关。我们进一步验证了PERP可能调节LUAD中B细胞的浸润从而影响LUAD的预后。为了确定 LUAD 中与 PERP 相关的信号通路，我们在低和高 PERP 表达数据集之间进行了基因组聚合分析 (GSEA)。LUAD细胞比癌旁细胞表达更高水平的PERP，并且PERP通过凋亡抑制A549细胞的增殖和转移。
结论： PERP可能通过抑制细胞凋亡影响肺腺癌的预后，并与免疫细胞浸润有关。