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ORIGINAL RESEARCH article
Front. Oncol.
Sec. Thoracic Oncology
Volume 14 - 2024 |
doi: 10.3389/fonc.2024.1438851
This article is part of the Research Topic Biomarker-Guided Strategies in NSCLC Immunotherapy View all 4 articles
The Causal Nexus between Diverse Smoking Statuses, Potential Therapeutic Targets, and NSCLC: Insights from Mendelian Randomization and Mediation Analysis
Provisionally accepted
ZhengHua Cao
1
Shengkun Zhao
1*
Tong Wu
1*
Huan Ding
2*
Zhiyu Tian
1
Feng Sun
2*
Zhuo Feng
1*
Shaodan Hu
2*
Li Shi
2*- 1 Changchun University of Chinese Medicine, Changchun, China
- 2 The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, Jilin Province, China
Objective: Lung cancer, the most prevalent malignancy, is typically diagnosed at an advanced stage.Smoking is a pivotal risk factor for NSCLC, yet the impact of various smoking statuses on NSCLC remains unclear. Thus, this study aims to explore whether different smoking statuses can causally influence NSCLC through effects on predictive targets, offering a novel perspective for NSCLC treatment. Methods: Employing dual-sample MR, MVMR, and TSMR approaches, we assessed the causal relationships between 13 distinct smoking statuses and NSCLC, using predicted potential therapeutic targets as mediators to further elucidate the causal interplay among them. Results: Among the 13 smoking statuses, current tobacco smoking, exposure to tobacco smoke outside the home, past tobacco smoking, and never smoked demonstrated causal relationships with NSCLC. MVMR analysis reveals that Current tobacco smoking is an independent risk factor for NSCLC. Utilizing NCAPD2, IL11RA, and MLC1 as mediators, IL11RA (22.2%) was found to potentially mediate the relationship between past tobacco smoking and NSCLC. Conclusion: This study, integrating bioinformatics and MR analysis, identified three potential predictive targets as mediators to investigate the causal relationships between different smoking statuses and NSCLC through potential therapeutic targets, providing new insights for the treatment and prevention of NSCLC.
Keywords: Different Smoking Statuses, NSCLC, Mendelian randomization, bioinformatics, Mediation analysis
Received: 26 May 2024; Accepted: 17 Oct 2024.
Copyright: © 2024 Cao, Zhao, Wu, Ding, Tian, Sun, Feng, Hu and Shi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Shengkun Zhao, Changchun University of Chinese Medicine, Changchun, China
Tong Wu, Changchun University of Chinese Medicine, Changchun, China
Huan Ding, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, 130021, Jilin Province, China
Feng Sun, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, 130021, Jilin Province, China
Zhuo Feng, Changchun University of Chinese Medicine, Changchun, China
Shaodan Hu, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, 130021, Jilin Province, China
Li Shi, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, 130021, Jilin Province, China
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