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

Autor: Demiray, A.G., Demiray, A.
Jazyk: angličtina
Rok vydání: 2023
Předmět:
cancer patient
frameshift mutation
Kaplan Meier method
microRNA 24
overall survival
protein p53
data analysis
tumor cell
cancer prognosis
Article
high throughput sequencing
computer assisted tomography
liquid biopsies
male
pancreas cancer
cancer diagnosis
controlled study
diagnostic test accuracy study
human
gene mutation
cancer survival
hidden Markov model
neutral mutation
DNA extraction
pancreas metastasis
clinical article
receiver operating characteristic
liquid biopsy
microRNA
missense mutation
adult
microRNA 146a
pilot study
Pancreatic cancer
bioinformatics
personalized medicine
DNA isolation
human tissue
pancreas adenocarcinoma
aged
female
sensitivity and specificity
real time polymerase chain reaction
gene expression
histopathology
next-generation sequencing
blood sampling
circulating free DNA
upregulation
Popis: Pancreatic cancer is highly aggressive and at the time of diagnosis, 80% of patients are in the metastatic stage. Personalize d 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 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. 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. 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. © 2023, Yuzuncu Yil Universitesi Tip Fakultesi. All rights reserved.
Databáze: OpenAIRE