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Exploring potential therapeutic targets for small cell lung cancer based on transcriptomics combined with Mendelian
Zhicheng Liao1, Pengcheng Jia1, Yifan Li1
1Department of Medical Oncology, Wenzhou TCM Hospital of Zhejiang Chinese Medical University, Wenzhou, China.
Objective:
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.
Insights
This study identified five co-expressed genes (CEGs) in small-cell lung cancer (SCLC) using transcriptomics and Mendelian randomization. One gene, PSRC1, is linked to poor survival, suggesting potential therapeutic targets for SCLC.
Area of Science:
- Oncology
- Genetics
- Bioinformatics
Background:
- Small-cell lung cancer (SCLC) remains a challenging disease with limited therapeutic options.
- Identifying novel genetic targets is crucial for developing effective SCLC treatments.
Purpose of the Study:
- To identify novel genetic targets in SCLC through transcriptomics and Mendelian randomization (MR) analysis.
- To explore the functional roles and therapeutic potential of identified genes in SCLC.
Main Methods:
- Utilized Gene Expression Omnibus (GEO) data for SCLC transcriptomics analysis to identify differentially expressed genes (DEGs).
- Applied MR analysis with expression quantitative trait loci (eQTL) and genome-wide association study (GWAS) data to identify SCLC-associated genes.
- Integrated DEGs and MR-identified genes to find co-expressed genes (CEGs) and performed enrichment analysis.
- Assessed immune cell infiltration using CIBERSORT and analyzed CEG correlations with immune cells.
- Conducted survival analysis on CEGs using an independent SCLC patient cohort.
Main Results:
- Identified 857 DEGs (443 up-regulated, 414 down-regulated) in SCLC.
- Discovered five CEGs (PSAT1, PSRC1, COLEC12, PLLP, HP) significantly associated with SCLC.
- Enrichment analyses revealed key functions and pathways involving CEGs.
- Found distinct immune cell infiltration patterns in SCLC and identified CEG-mediated immune regulation mechanisms.
- Survival analysis indicated PSRC1 is significantly correlated with overall SCLC survival, with higher expression linked to lower survival rates.
Conclusions:
- The identified CEGs and their associated pathways represent potential therapeutic targets for SCLC.
- Targeting specific molecular pathways involving these CEGs may lead to novel SCLC interventions.
- PSRC1 emerges as a promising prognostic biomarker and potential therapeutic target in SCLC.
