Evaluation Of Serum MicroRNA Levels And Mutations Using Next-Generation Sequencing Of Liquid Biopsies From Metastatic Pancreatic Cancer Patients: A Turkish Pilot Study

INTRODUCTION: Pancreatic cancer is highly aggressive and at the time of diagnosis, 80% of patients are in the metastatic stage. Personalized therapy guided by genomic biomarkers for pancreatic cancer has only recently begun to be investigated.This study aimed to comprehensively identify possible activating and pathological mutations in metastatic pancreatic cancer with NGS of liquid biopsies and to investigate miRNAs and mutations as therapeutic targets as we evaluated their relationships and effect on prognoses
METHODS: Seventeen patients and 20 healthy volunteers were included in the study. Blood samples were taken from the patients, cell-free DNA was isolated from the serum, and mutation profiles were analyzed by NGS. Serum miRNA levels were analyzed by isolating circulating miRNA from the same samples from all groups.
RESULTS: In patients with G288G synonymous mutants in the HNF1A gene compared to non-mutant patients, miR-17, miR-24, and miR-150 levels were found to be statistically significantly lower;The miR-17 and miR-146a levels of patients with a TP53 gene Pro72Arg mutation were found to be statistically significantly higher than that of the non-mutant group Survival was lower with the c.2472 C>T mutation located in exon 18 of the PDGFRA gene; higher in patients with P72R mutations in the TP53 gene and those with miRNA 17 and 146 upregulation carrying this mutation.
DISCUSSION AND CONCLUSION: This study is clinically meaningful in revealing possible pathogenic mutations detected in tumor cells circulating in metastatic pancreatic cancer, both in terms of prognostic value and whether the information can be used to target treatment, including gene therapy.