Circadian rhythm-associated clinical relevance and Tumor Microenvironment of Non-small Cell Lung Cancer

Li, Ming; Chen, Zhencong; Jiang, Tian; Yang, Xiaodong; Du, Yajing; Liang, Jiaqi; Wang, Lin; Xi, Junjie; Lin, Miao; Feng, Mingxiang

doi:10.7150/jca.52454

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J Cancer 2021; 12(9):2582-2597. doi:10.7150/jca.52454 This issue Cite

Research Paper

Circadian rhythm-associated clinical relevance and Tumor Microenvironment of Non-small Cell Lung Cancer

Ming Li, MD^1*, Zhencong Chen, MD^1*, Tian Jiang, Ph.D.^1*, Xiaodong Yang, MD², Yajing Du, MS³, Jiaqi Liang, MS¹, Lin Wang, Ph.D.¹, Junjie Xi, MD¹, Miao Lin, MD^1✉, Mingxiang Feng, MD^1✉

1. Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.
2. Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, Shanghai, 200433, People's Republic of China.
3. Center for Tumor Diagnosis and Therapy, Jinshan Hospital, Fudan University, Shanghai 201508, People's Republic of China.
*These authors contributed equally to this work.

Citation:

Li M, Chen Z, Jiang T, Yang X, Du Y, Liang J, Wang L, Xi J, Lin M, Feng M. Circadian rhythm-associated clinical relevance and Tumor Microenvironment of Non-small Cell Lung Cancer. J Cancer 2021; 12(9):2582-2597. doi:10.7150/jca.52454. https://www.jcancer.org/v12p2582.htm

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Abstract

Objective: We aimed to explore the prognostic implication for non-small cell lung cancer (NSCLC) based on the expression profiles of circadian clock-related genes (CCRGs), and describe the changes of immune infiltration and cell functions of related to the circadian rhythm.

Methods: Univariate and multivariate Cox proportional hazard regression were performed to determine a CCRGs risk-score significantly correlated with overall survival (OS) of the training set and validation set. GO, KEGG, and GSVA indicated discrepant changes in cellular processes and signaling pathways associated with these CCRGs. Immune cell infiltration and mutation rates were investigated by the online analysis platform and the algorithm provided by works of literature.

Results: The signature-based on ten-gene signatures could independently predict the OS both in TCGA lung adenocarcinoma (p < 0.001, HR: 1.228, 95% CI: 1.158 to 1.302) and lung squamous cell carcinoma (p < 0.001, HR: 2.501, 95% CI: 2.010 to 3.117), respectively. The circadian oscillations driven by CCRGs could disturb the metabolism and cellular functions of cancer cells. The infiltration level of critical cells in specific anti-tumor immunity process was suppressed apparently. In contrast, the infiltrating of inflammatory cells and immune cells with negative regulatory effects were promoted in the high-risk group. CCRGs were evolutionarily conserved with low mutation rates, which brought difficulties to explore therapeutic targets.

Conclusion: We identified and validated a circadian rhythm signature to described clinical relevance and tumor microenvironment of NSCLC, which revealed that circadian rhythms might play an influential role in the NSCLC.

Keywords: circadian rhythm, non-small cell lung cancer, signature, prognosis, cellular function, immune infiltration

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APA

Li, M., Chen, Z., Jiang, T., Yang, X., Du, Y., Liang, J., Wang, L., Xi, J., Lin, M., Feng, M. (2021). Circadian rhythm-associated clinical relevance and Tumor Microenvironment of Non-small Cell Lung Cancer. Journal of Cancer, 12(9), 2582-2597. https://doi.org/10.7150/jca.52454.

ACS

Li, M.; Chen, Z.; Jiang, T.; Yang, X.; Du, Y.; Liang, J.; Wang, L.; Xi, J.; Lin, M.; Feng, M. Circadian rhythm-associated clinical relevance and Tumor Microenvironment of Non-small Cell Lung Cancer. J. Cancer 2021, 12 (9), 2582-2597. DOI: 10.7150/jca.52454.

NLM

CSE

Li M, Chen Z, Jiang T, Yang X, Du Y, Liang J, Wang L, Xi J, Lin M, Feng M. 2021. Circadian rhythm-associated clinical relevance and Tumor Microenvironment of Non-small Cell Lung Cancer. J Cancer. 12(9):2582-2597.

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