Downregulation of the circadian Period family genes is positively correlated with poor head and neck squamous cell carcinoma prognosis

ABSTRACT

We investigated the relationship between head and neck squamous cell carcinoma (HNSCC) and the mRNA and protein expression levels of the circadian genes of the Period (Per) family, Per1, Per2 and Per3. Tissue sections of HNSCC and normal head and neck tissues from two patient cohorts from two different hospitals were collected to assess the mRNA and protein expressions of the three Per family genes using real-time quantitative PCR (RT-PCR) and immunohistochemistry (IHC). The clinicopathological features and disease prognosis for the latter cohort were analyzed through IHC and statistical methods. Protein positive expression levels of the three Per family genes in HNSCC tissues was found to be approximately two times lower than that in normal tissues (p < .01). Moreover, patients with locally advanced HNSCC showed significantly greater downregulation of Per1, Per2 and Per3 mRNA expression levels as compared to patients with early-stage cancer (p < .05). Immunohistochemical examination of HNSCC patient tissues revealed a positive correlation between the Per family protein expression and the clinical tumor staging (p < .05). In addition, the Per protein-positive expression group showed higher 3-year survival rates [overall survival (OS) and progression-free survival (PFS)] as assessed by Kaplan-Meier plots and statistical analysis (p < .05). Our findings confirm the positive correlation between Per family gene expression and survival outcomes and support their role as prognostic markers for HNSCC.

KEYWORDS:

• Head and neck squamous cell carcinoma (HNSCC)
• normal tissues of the head and neck
• circadian gene
• Per1
• Per2
• Per3
• real-time quantitative PCR
• immunohistochemistry

Acknowledgments

The authors would like to thank the Clinical Research Center of the Guizhou Medical University.

Availability of data and materials

All data generated or analyzed during this study are included in this published article.

Authors’ contributions

Yuanyuan Li analyzed and interpreted the patient data,and drafted the manuscript. Ye Tian and Feng Jin gived advices on conception and design.Jian Jiang Zhou, Fang Yu and Xiao Yan He provided technical guidance. Xiao Feng Duan provided tissue samples. Rui Wang collected the patient data. All authors read and approved the final manuscript.

Competing interests

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Ethics approval and consent to participate

All procedures were conducted with the approval of the Ethics Committee of the Guizhou Provincial Cancer Hospital.

Additional information

Funding

This study was supported by the Guizhou Provincial Department of Education Innovation Group Major Research Project [Guizhou Teaching grant no. KY[2017]38].