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Objective <p>This study aimed to explore potential associations between polyunsaturated fatty acid (PUFA) metabolism and laryngeal cancer (LC) using a combination of Mendelian randomization (MR) and integrative bioinformatics, while investigating its potential immunogenic implications.</p> Methods <p>Transcriptomic data from the GEO database were integrated to identify differentially expressed genes (DEGs) in LC. Gene Set Enrichment Analysis (GSEA) was performed in addition to Gene Ontology and KEGG enrichment analyses to characterize biological functions. MR analysis was employed to assess the potential causal link between PUFA metabolism and LC risk. PUFA-associated genes were screened for druggability using the DGIdb database. Furthermore, an lncRNA–miRNA–mRNA (ceRNA) regulatory network was constructed, and immune cell infiltration in LC was profiled using CIBERSORT with LM22 signature matrix to uncover immunoregulatory associations with PUFA pathway genes.</p> Results <p>A total of 730 DEGs were identified from a combined cohort of 30 LC and 31 normal samples. GSEA and enrichment analysis revealed significant involvement in fatty acid metabolism and immune-related pathways. MR analysis demonstrated a statistically significant but modest association between PUFA metabolism and LC risk (OR = 0.9996, 95% CI = 0.9992–0.9999, <i>p</i> = 0.020). A network of key PUFA pathway genes (e.g., ADH1B, ADH1A, ALDH7A1, CYP2J2, PTGIS) was linked with multiple drug targets. A focused sub-network of regulatory interactions among lncRNAs, miRNAs, and mRNAs was elucidated. Immune infiltration analysis revealed distinct correlations between pathway gene expression and immune cell populations, particularly showing PTGIS positively correlated with activated mast cells and negatively with naive B cells.</p> Conclusions <p>Our findings suggest a potential mechanistic link between PUFA metabolism and LC susceptibility, generating hypotheses that PUFA-associated pathways may modulate immune microenvironment characteristics. This computational study provides preliminary insights into potential immunometabolic therapeutic strategies in laryngeal cancer that warrant experimental validation.</p>

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An integrative bioinformatic and Mendelian randomization study exploring the role of polyunsaturated fatty acid metabolism in laryngeal cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月29日

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  • Lina Peng,
  • Haibin Ma,
  • Longchao Qin,
  • Qian Zhao,
  • Xueyan Ren,
  • Zihao Wang,
  • Jing Hu,
  • Haiping Han

摘要

Objective

This study aimed to explore potential associations between polyunsaturated fatty acid (PUFA) metabolism and laryngeal cancer (LC) using a combination of Mendelian randomization (MR) and integrative bioinformatics, while investigating its potential immunogenic implications.

Methods

Transcriptomic data from the GEO database were integrated to identify differentially expressed genes (DEGs) in LC. Gene Set Enrichment Analysis (GSEA) was performed in addition to Gene Ontology and KEGG enrichment analyses to characterize biological functions. MR analysis was employed to assess the potential causal link between PUFA metabolism and LC risk. PUFA-associated genes were screened for druggability using the DGIdb database. Furthermore, an lncRNA–miRNA–mRNA (ceRNA) regulatory network was constructed, and immune cell infiltration in LC was profiled using CIBERSORT with LM22 signature matrix to uncover immunoregulatory associations with PUFA pathway genes.

Results

A total of 730 DEGs were identified from a combined cohort of 30 LC and 31 normal samples. GSEA and enrichment analysis revealed significant involvement in fatty acid metabolism and immune-related pathways. MR analysis demonstrated a statistically significant but modest association between PUFA metabolism and LC risk (OR = 0.9996, 95% CI = 0.9992–0.9999, p = 0.020). A network of key PUFA pathway genes (e.g., ADH1B, ADH1A, ALDH7A1, CYP2J2, PTGIS) was linked with multiple drug targets. A focused sub-network of regulatory interactions among lncRNAs, miRNAs, and mRNAs was elucidated. Immune infiltration analysis revealed distinct correlations between pathway gene expression and immune cell populations, particularly showing PTGIS positively correlated with activated mast cells and negatively with naive B cells.

Conclusions

Our findings suggest a potential mechanistic link between PUFA metabolism and LC susceptibility, generating hypotheses that PUFA-associated pathways may modulate immune microenvironment characteristics. This computational study provides preliminary insights into potential immunometabolic therapeutic strategies in laryngeal cancer that warrant experimental validation.