Integration of multi-omics data to unveil the molecular landscape and role of piRNAs in early-onset colorectal cancer

  • 0Department of Colorectal Surgery and Oncology, The Second Affiliated Hospital, School of Public Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

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Summary

This summary is machine-generated.

Early-onset colorectal cancer (EOCRC) shows rising incidence and aggression. PIWIL1-associated piRNAs, particularly FR019089, are key regulators of EOCRC metastasis and invasion, offering potential as prognostic biomarkers.

Area Of Science

  • Oncology
  • Molecular Biology
  • Genomics

Background

  • Early-onset colorectal cancer (EOCRC) incidence is increasing, with more metastatic and invasive cases.
  • Understanding the molecular drivers of EOCRC aggressiveness is crucial.

Purpose Of The Study

  • To elucidate the molecular mechanisms underlying EOCRC using comprehensive multi-omics profiling.
  • To identify key drivers of metastatic and invasive potential in EOCRC.

Main Methods

  • Multi-omics profiling (genome, epigenome, transcriptome) of 515 colorectal cancer (CRC) cases (69 EOCRC, 446 late-onset CRC [LOCRC]).
  • Validation using RNA-seq, scRNA-seq, in vitro functional assays, and survival analysis.
  • Investigated PIWIL1/piRNA expression and function in EOCRC.

Main Results

  • EOCRC shares a similar mutational landscape with LOCRC but shows distinct chromosomal deletions and metabolic reprogramming.
  • PIWIL1 and its downstream piRNAs (FR019019, FR019089, FR132045) were identified as EOCRC-specific, with lower expression in EOCRC.
  • Overexpression of FR019089/FR019019 suppressed EOCRC cell migration and invasion; low FR019089 correlated with poorer survival.

Conclusions

  • Multi-omics analysis reveals PIWIL1-associated piRNAs modulate EOCRC metastasis and invasion.
  • FR019089 demonstrates potential as a prognostic biomarker for risk stratification and management of EOCRC patients.

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