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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1464259

Exploring potential therapeutic targets for small cell lung cancer based on Transcriptomics combined with Mendelian randomisation analysis

Provisionally accepted
Zhicheng Liao Zhicheng Liao Pengcheng Jia Pengcheng Jia Yifan Li Yifan Li *Zhihui Zheng Zhihui Zheng *Jizhou Zhang Jizhou Zhang *
  • Wenzhou TCM Hospital of Zhejiang Chinese Medical University, Wenzhou, Zhejiang Province, China

The final, formatted version of the article will be published soon.

    The main objective of this study was to explore and identify new genetic targets in small-cell lung cancer (SCLC) through transcriptomics analysis and Mendelian randomization (MR) analysis, which will help in the subsequent development of new therapeutic interventions. Methods: In this study, we extracted the SCLC dataset from the Gene Expression Omnibus (GEO) database, processed the data, and screened out differentially expressed genes (DEGs) using R software. Based on expression quantitative trait loci data and the genome-wide association study data of SCLC, MR analysis was used to screen the genes closely related to SCLC disease, which intersect with DEGs to obtain co-expressed genes (CEGs), and the biological functions and pathways of CEGs were further explored by enrichment analysis. In addition, the CIBERSORT algorithm was applied to assess the level of immune cell infiltration in SCLC and to analyze the correlation between CEGs and immune cells. Meanwhile, we performed a survival analysis on these five CEGs using an independent cohort of SCLC patients. Finally, the results for the target genes were validated. Results: In this study, 857 DEGs were identified, including 443 up-regulated and 414 down-regulated genes, and 5 CEGs (PSAT1, PSRC1, COLEC12, PLLP, HP) that were significantly associated with SCLC were identified through further intersecting. The results of enrichment analyses indicated that CEGs play important roles in several key functions and pathways.Immune-cell-related analysis revealed the unique distribution of immune cell infiltration in SCLC and the mechanism of immune cell regulation by CEGs. Survival analysis results indicated that PSRC1 was significantly correlated with the overall survival of SCLC, and the survival rate of the high-expression group was markedly lower than that of the low-expression group. Finally, the consistency of the results between the validation group analyses and MR analysis confirmed that the results of this study is reliable. Conclusion: The CEGs and their associated functions and pathways screened in this study may be potential targets of therapeutic intervention in SCLC by targeting specific molecular pathways.

    Keywords: Small Cell Lung Cancer, Differentially expressed genes, expression quantitative trait loci, Mendelian Randomization Analysis, Co-expressed genes, Immune Cell Infiltration

    Received: 13 Jul 2024; Accepted: 27 Dec 2024.

    Copyright: © 2024 Liao, Jia, Li, Zheng and Zhang. 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:
    Yifan Li, Wenzhou TCM Hospital of Zhejiang Chinese Medical University, Wenzhou, Zhejiang Province, China
    Zhihui Zheng, Wenzhou TCM Hospital of Zhejiang Chinese Medical University, Wenzhou, Zhejiang Province, China
    Jizhou Zhang, Wenzhou TCM Hospital of Zhejiang Chinese Medical University, Wenzhou, Zhejiang Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.