Research Paper|Volume 14, Issue 22|pp 9056—9089

Circadian rhythm-related factors of PER and CRY family genes function as novel therapeutic targets and prognostic biomarkers in lung adenocarcinoma

Chin-Chou Wang^2,^3,⁴, Wei-Hsun Lin¹, Su-Chi Ku^5,^6,⁷, Wan-Jou Shen⁸, Hoang Dang Khoa Ta⁶, Gangga Anuraga^6,⁹, Fang-Wen Liu¹, Chiu-Fan Shen², Shu-He Wang¹, Chia-Chen Yang¹, Chih-Yang Wang^5,^6,¹⁰, Wei-Jan Wang^1,¹¹

¹Department of Biological Science and Technology, China Medical University, Taichung 40676, Taiwan
²Divisions of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
³Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
⁴Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi 613016, Taiwan
⁵Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
⁶Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, Taiwan
⁷School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
⁸Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung 40402, Taiwan
⁹Department of Statistics, Faculty of Science and Technology, Universitas PGRI Adi Buana, Surabaya, East Java 60234, Indonesia
¹⁰TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 11031, Taiwan
¹¹Research Center for Cancer Biology, China Medical University, Taichung 40676, Taiwan

* Equal contribution

Received: January 26, 2022Accepted: November 2, 2022Published: November 16, 2022

https://doi.org/10.18632/aging.204386

Copyright: © 2022 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The period (PER) and cryptochrome (CRY) families play critical roles in circadian rhythms. The imbalance of circadian factors may lead to the occurrence of cancer. Expressions of PER and CRY family members decrease in various cancers. Nevertheless, expression levels, genetic variations, and molecular mechanisms of PER and CRY family members in lung adenocarcinoma (LUAD) and their correlations with prognoses and immune infiltration in LUAD patients are still unclear. In this study, to identify their biological functions in LUAD development, comprehensive high-throughput techniques were applied to analyze the relationships of expressions of PER and CRY family members with genetic variations, molecular mechanisms, and immune infiltration. The present results showed that transcription levels of PER1 and CRY2 in LUAD were significantly downregulated. High expression levels of PER2, PER3, CRY1, and CRY2 indicated longer overall survival. Some cancer signaling pathways were related to PER and CRY family members, such as cell-cycle, histidine metabolism, and progesterone-mediated oocyte maturation pathways. Expressions of PER and CRY family members significantly affected the infiltration of different immune cells. In conclusion, our findings may help better understand the molecular basis of LUAD, and provide new perspectives of PER and CRY family members as novel biomarkers for LUAD.