miR-194 as predictive biomarker of responsiveness to neoadjuvant chemoradiotherapy in patients with locally advanced rectal adenocarcinoma.
Edoardo D'AngeloCarlo ZanonFrancesca SensiMaura DigitoMassimo RuggeMatteo FassanMarco ScarpaSalvatore PucciarelliDonato NittiMarco AgostiniPublished in: Journal of clinical pathology (2017)
Using biopsy samples collected at diagnosis, mir-194 was significantly upregulated in patients responding to treatment (p value=0.016). The data was confirmed with qRT-PCR (p value=0.0587) and ISH (p value=0.026). Protein-protein interaction network and pathway enrichment analysis reveal a possible mechanism of susceptibility to pCRT involving Wnt pathway via its downstream mediator TRAF6. Finally, we interrogated the Comparative Toxicogenomics Database database in order to identify those chemical compounds able to mimic the biological effects of miR-194 as new possible therapeutic option in LARC treatment. The present study combining miRNA expression profiling with integrative computational biology identified miR-194 as predictive biomarker of response to pCRT. Using known and predicted drug mechanism of action, we then identified possible chemical compounds for further in vitro validation.
Keyphrases
- locally advanced
- cell proliferation
- rectal cancer
- long non coding rna
- long noncoding rna
- protein protein
- neoadjuvant chemotherapy
- squamous cell carcinoma
- end stage renal disease
- radiation therapy
- small molecule
- ejection fraction
- stem cells
- phase ii study
- newly diagnosed
- chronic kidney disease
- single cell
- prognostic factors
- machine learning
- dna methylation
- lymph node
- patient reported outcomes
- transcription factor
- network analysis
- artificial intelligence
- study protocol
- replacement therapy