Exploring potential therapeutic targets for small cell lung cancer based on transcriptomics combined with Mendelian randomization analysis
ObjectiveThe 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.MethodsIn this study,...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1464259/full |
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| author | Zhicheng Liao Pengcheng Jia Yifan Li Zhihui Zheng Jizhou Zhang |
| author_facet | Zhicheng Liao Pengcheng Jia Yifan Li Zhihui Zheng Jizhou Zhang |
| author_sort | Zhicheng Liao |
| collection | DOAJ |
| description | ObjectiveThe 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.MethodsIn 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.ResultsIn 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.ConclusionThe 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. |
| format | Article |
| id | doaj-art-8aabf5d62af94b20ae569aa5b099b446 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-8aabf5d62af94b20ae569aa5b099b4462025-01-13T06:10:31ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14642591464259Exploring potential therapeutic targets for small cell lung cancer based on transcriptomics combined with Mendelian randomization analysisZhicheng LiaoPengcheng JiaYifan LiZhihui ZhengJizhou ZhangObjectiveThe 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.MethodsIn 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.ResultsIn 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.ConclusionThe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1464259/fullsmall cell lung cancerdifferentially expressed genesexpression quantitative trait lociMendelian randomization analysisco-expressed genesimmune cell infiltration |
| spellingShingle | Zhicheng Liao Pengcheng Jia Yifan Li Zhihui Zheng Jizhou Zhang Exploring potential therapeutic targets for small cell lung cancer based on transcriptomics combined with Mendelian randomization analysis Frontiers in Immunology small cell lung cancer differentially expressed genes expression quantitative trait loci Mendelian randomization analysis co-expressed genes immune cell infiltration |
| title | Exploring potential therapeutic targets for small cell lung cancer based on transcriptomics combined with Mendelian randomization analysis |
| title_full | Exploring potential therapeutic targets for small cell lung cancer based on transcriptomics combined with Mendelian randomization analysis |
| title_fullStr | Exploring potential therapeutic targets for small cell lung cancer based on transcriptomics combined with Mendelian randomization analysis |
| title_full_unstemmed | Exploring potential therapeutic targets for small cell lung cancer based on transcriptomics combined with Mendelian randomization analysis |
| title_short | Exploring potential therapeutic targets for small cell lung cancer based on transcriptomics combined with Mendelian randomization analysis |
| title_sort | exploring potential therapeutic targets for small cell lung cancer based on transcriptomics combined with mendelian randomization analysis |
| topic | small cell lung cancer differentially expressed genes expression quantitative trait loci Mendelian randomization analysis co-expressed genes immune cell infiltration |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1464259/full |
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