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Background <p>Pancreatic cancer (PC) is characterized by a profoundly immunosuppressive and fibrotic tumor microenvironment, driven largely by cancer-associated fibroblasts (CAFs). While microRNAs (miRNAs) are key regulators in PC, their specific roles in stromal fibrosis remain poorly understood. This study aims to investigate the prognostic and fibrotic relevance of miR-4787-3p and miR-581 in PC.</p> Methods <p>We identified differentially expressed miRNAs from The Cancer Genome Atlas (TCGA) database. MiR-4787-3p and miR-581 were selected for their prognostic value using Cox regression and Kaplan-Meier analysis. Their expression was validated in vitro using a co-culture model of PC cells and CAFs, and in clinical blood and tissue samples via RT-PCR, with correlations to clinical-pathological features and fibrosis markers (TGF-β1, COL1A1) assessed.</p> Results <p>TCGA analysis revealed significant downregulation of both miRNAs in PC tissues, which correlated strongly with poor patient survival. Mechanistically, their expression was suppressed in PC cell lines co-cultured with CAFs and inversely correlated with TGF-β1 and COL1A1 levels. Consistent with these findings, miR-4787-3p and miR-581 levels were markedly lower in PC patient tissues and blood samples compared to controls, with the lowest expression observed in high-fibrosis tissues. Both miRNAs demonstrated high sensitivity and specificity for distinguishing PC from non-cancerous controls and for identifying fibrosis within tumors.</p> Conclusion <p>The downregulation of miR-4787-3p and miR-581 is a hallmark of pancreatic cancer, closely associated with tumor fibrosis and poor prognosis. These miRNAs represent promising circulating and tissue biomarker candidates for diagnosing PC and evaluating its fibrotic burden, suggesting potential utility for early detection and personalized treatment strategies.</p>

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miR-4787-3p and miR-581 as predictive biomarkers for fibrosis and prognosis in pancreatic cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月7日

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  • Peng Chen,
  • Meng Pan,
  • Guanglong Hu,
  • Zhengchao Shen,
  • Xiaolong Zeng,
  • Yuanxiang Zhang,
  • Zhiyuan Chen,
  • Chao Zhang,
  • Xiaoming Wang

摘要

Background

Pancreatic cancer (PC) is characterized by a profoundly immunosuppressive and fibrotic tumor microenvironment, driven largely by cancer-associated fibroblasts (CAFs). While microRNAs (miRNAs) are key regulators in PC, their specific roles in stromal fibrosis remain poorly understood. This study aims to investigate the prognostic and fibrotic relevance of miR-4787-3p and miR-581 in PC.

Methods

We identified differentially expressed miRNAs from The Cancer Genome Atlas (TCGA) database. MiR-4787-3p and miR-581 were selected for their prognostic value using Cox regression and Kaplan-Meier analysis. Their expression was validated in vitro using a co-culture model of PC cells and CAFs, and in clinical blood and tissue samples via RT-PCR, with correlations to clinical-pathological features and fibrosis markers (TGF-β1, COL1A1) assessed.

Results

TCGA analysis revealed significant downregulation of both miRNAs in PC tissues, which correlated strongly with poor patient survival. Mechanistically, their expression was suppressed in PC cell lines co-cultured with CAFs and inversely correlated with TGF-β1 and COL1A1 levels. Consistent with these findings, miR-4787-3p and miR-581 levels were markedly lower in PC patient tissues and blood samples compared to controls, with the lowest expression observed in high-fibrosis tissues. Both miRNAs demonstrated high sensitivity and specificity for distinguishing PC from non-cancerous controls and for identifying fibrosis within tumors.

Conclusion

The downregulation of miR-4787-3p and miR-581 is a hallmark of pancreatic cancer, closely associated with tumor fibrosis and poor prognosis. These miRNAs represent promising circulating and tissue biomarker candidates for diagnosing PC and evaluating its fibrotic burden, suggesting potential utility for early detection and personalized treatment strategies.