Period2 is associated with immune cell infiltration and is a potential diagnostic and prognostic marker for hepatocellular carcinoma

Xiaolin Chen; Qiaosu Zhao; Haibiao Wang; Kaijie Qiu; Xi Deng; Feng Xu

doi:10.3389/fmolb.2023.1264553

Period2 is associated with immune cell infiltration and is a potential diagnostic and prognostic marker for hepatocellular carcinoma

Front Mol Biosci. 2023 Nov 21:10:1264553. doi: 10.3389/fmolb.2023.1264553. eCollection 2023.

Authors

Xiaolin Chen¹, Qiaosu Zhao¹, Haibiao Wang², Kaijie Qiu², Xi Deng³, Feng Xu¹

Affiliations

¹ Department of Gastroenterology, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, China.
² Department of Hepatobiliary Surgery, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, China.
³ Department of Histopathology, Ningbo Clinical Pathology Diagnostic Center, Ningbo, China.

Abstract

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.

Keywords: Methylation; Period2; hepatocellular carcinoma; immune cell infiltration; prognostic biomarker; tumor microenvironment.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and of this article. This work was supported by the Ningbo Natural Fund Project (grant no. 2021J295, 2022J261), Ningbo Medical Center Lihuili Hospital, “Huili Fund” (2022ZD005) and Ninghai County Social Development Science and Technology Project (202301).