Exploring shared genetic factors and prognostic biomarkers in pancreatic cancer and non-alcoholic fatty liver disease: Focus on hsa-miR-29c-3p and COL11A1 axis

Abstract

Background

Pancreatic cancer (PC) has a high fatality rate and is often diagnosed late. Obesity is a significant risk factor for PC, leading to inflammation and altered gut microbiota that may contribute to its development. Non-alcoholic fatty liver disease (NAFLD) is linked to obesity but its association with PC risk remains unclear. Both PC and NAFLD may share genetic factors, and research is ongoing to understand their underlying mechanisms through comprehensive sequencing data analysis.

Method

The study utilized bioinformatics tools and databases to analyze gene expression data from PC and obese NAFLD. Differential gene expression, enrichment analysis, and protein-protein interaction analysis identified potential biomarkers and therapeutic targets. Survival analysis validated hub genes, and correlation analysis was used to evaluate the relationships between immune cells and PC. Prognostic miRNA analysis and drug sensitivity assessment revealed predictive biomarkers for drug efficacy. Statistical methods were applied to evaluate significance.

Results

The study compared gene expression profiles between PC and NAFLD, revealing 58 common genes. Important pathways such as tyrosine metabolism, fatty acid degradation, and glycolysis/gluconeogenesis were revealed by enrichment analysis to be connected to the common genes in both diseases. Notably, five hub genes (MARCO, COL11A1, CDCP1, CLEC5A, COL6A6) emerged as potential players in PC and NAFLD. Survival analysis confirmed their significance in PC prognosis. The study also identified hsa-miR-29c-3p as a promising prognostic biomarker targeting COL11A1 in PC, along with the long non-coding RNA (IncRNA) taurine-upregulated gene 1 (TUG1) axis, which was associated with poor survival of PC patients. The clinical significance of hsa-miR-29c-3p was highlighted by Receiver Operating Characteristic (ROC) curve analysis, which also provided insight into the relationships between chemo-resistance, particularly with regard to Capecitabine.

Conclusion

The study identified the shared genetic factor COL11A1 as a possible biomarker in PC and NAFLD. Notably, hsa-miR-29c-3p emerged as a promising prognostic biomarker targeting COL11A1 in PC, with implications for patient survival. These findings contribute to our understanding of the underlying mechanisms and may offer clinical significance in predicting outcomes and guiding therapeutic approaches for these challenging diseases.