Table2_Period2 is associated with immune cell infiltration and is a potential diagnostic and prognostic marker for hepatocellular carcinoma.XLSX

Background: Hepatocellular carcinoma (HCC) health challenge worldwide. Many studies showed that circadian rhythms play a critical role in tumor development. This study aimed to investigate the role of the circadian gene period2 (PER2) in HCC development and explore the possible mechanisms involved.
Methods: From fresh HCC tissues and paired paracancerous tissues, we measured PER2 mRNA and protein expression levels and calculated the correlations between PER2 expression and clinicopathological parameters in patients with HCC. We used transcriptome data from The Cancer Genome Atlas to mine the PER2 gene, including single gene difference analysis, single gene co-expression analysis, gene set enrichment analysis, immune infiltration analysis, and methylation analysis to explore its role and mechanism in HCC occurrence and development.
Results: PER2 expression levels were significantly lower in HCC tissues than in the paired paracancerous tissues. PER2 expression in HCC significantly correlated with neural invasion, Child-Pugh classification, and China liver cancer staging stage in HCC patients. The differentially expressed genes associated with PER2 were significantly enriched in mitochondrial oxidative phosphorylation, transcriptional translation, amino acid metabolism, and other related pathways. PER2 expression levels significantly correlated with immune cell infiltration and immune checkpoint genes and positively correlated with TP53 expression in HCC tissues. The DNA methylation status in eight CpG islands of the PER2 gene was associated with HCC outcomes.
Conclusion: PER2 is a potential diagnostic and prognostic biomarker and a promising therapeutic target in HCC.

背景：肝细胞癌（Hepatocellular carcinoma, HCC）是全球性的健康挑战。诸多研究证实，昼夜节律在肿瘤发生发展过程中发挥关键调控作用。本研究旨在探讨昼夜节律基因period2（PER2）在肝细胞癌发生发展中的作用，并揭示其潜在的分子机制。
方法：本研究收集新鲜肝细胞癌组织及配对癌旁组织，检测PER2的mRNA与蛋白表达水平，分析肝细胞癌患者的PER2表达水平与临床病理参数之间的相关性。本研究借助癌症基因组图谱（The Cancer Genome Atlas, TCGA）的转录组数据对PER2基因进行挖掘分析，涵盖单基因差异分析、单基因共表达分析、基因集富集分析、免疫浸润分析以及甲基化分析，以探究其在肝细胞癌发生发展中的作用与潜在机制。
结果：肝细胞癌组织中的PER2表达水平显著低于配对的癌旁组织。肝细胞癌患者的PER2表达水平与神经侵犯、Child-Pugh分级及中国肝癌分期显著相关。与PER2相关的差异表达基因显著富集于线粒体氧化磷酸化、转录翻译、氨基酸代谢等多条相关通路。PER2表达水平与免疫细胞浸润及免疫检查点基因表达显著相关，且在肝细胞癌组织中与TP53表达呈正相关。PER2基因8个CpG岛的DNA甲基化状态与肝细胞癌患者的预后密切相关。
结论：PER2可作为肝细胞癌潜在的诊断与预后生物标志物，同时也是极具前景的肝细胞癌治疗靶点。