Advances in medical sciences · 2025
Genetic instability at the PTEN locus and altered miRNA-21 and miRNA-200a expression in gastric cancer patients in Poland.
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Dzikowiec Magdalena, Galant Sandra, Lik Przemysław, Migdalska-Sęk Monika, Nejc Dariusz, Piekarski Janusz, Majos Alicja, Brzeziańska-Lasota Ewa, Pastuszak-Lewandoska Dorota
Аннотация
PURPOSE: Gastric cancer is often diagnosed late, and is associated with poor long-term prognosis. The aim of the study was to look for non-invasive potential biomarkers involved in gastric carcinogenesis, with diagnostic or prognostic significance.
MATERIAL/METHODS: Gastric tissue samples, from three different regions of the stomach, including the primary tumor, macroscopically unchanged gastric tissues, as well as serum, were collected from patients diagnosed with gastric cancer. Serum samples were also obtained from a control group. The analyzed parameters were: expression levels of PTEN, miRNA-21 and miRNA-200a using qPCR method and the frequency of LOH/MSI at the PTEN locus using four microsatellite markers.
RESULTS: The obtained results revealed significantly decreased expression of PTEN in gastric tumor tissue and statistically significant differences between the studied tissue samples from different stomach regions. PTEN expression in patients with LOH/MSI was decreased two-fold compared to patients without genetic instability, indicating a potential mechanism of gene silencing. Another mechanism of PTEN silencing could be due to miRNA activity: significant negative correlations were found between PTEN and the studied miRNAs expression levels. In serum, miRNA-21 expression was increased in the group of patients, while miRNA-200a expression was decreased, and the differences were statistically significant compared to controls. Receiver operating characteristic curve analysis for miRNA-200a revealed 92 % sensitivity and 77 % specificity.
CONCLUSIONS: The obtained results suggest that miRNA-21 and miRNA-200a could be considered as diagnostic biomarkers differentiating patients with gastric cancer from healthy individuals; however, it should be verified on a larger group of patients.
MATERIAL/METHODS: Gastric tissue samples, from three different regions of the stomach, including the primary tumor, macroscopically unchanged gastric tissues, as well as serum, were collected from patients diagnosed with gastric cancer. Serum samples were also obtained from a control group. The analyzed parameters were: expression levels of PTEN, miRNA-21 and miRNA-200a using qPCR method and the frequency of LOH/MSI at the PTEN locus using four microsatellite markers.
RESULTS: The obtained results revealed significantly decreased expression of PTEN in gastric tumor tissue and statistically significant differences between the studied tissue samples from different stomach regions. PTEN expression in patients with LOH/MSI was decreased two-fold compared to patients without genetic instability, indicating a potential mechanism of gene silencing. Another mechanism of PTEN silencing could be due to miRNA activity: significant negative correlations were found between PTEN and the studied miRNAs expression levels. In serum, miRNA-21 expression was increased in the group of patients, while miRNA-200a expression was decreased, and the differences were statistically significant compared to controls. Receiver operating characteristic curve analysis for miRNA-200a revealed 92 % sensitivity and 77 % specificity.
CONCLUSIONS: The obtained results suggest that miRNA-21 and miRNA-200a could be considered as diagnostic biomarkers differentiating patients with gastric cancer from healthy individuals; however, it should be verified on a larger group of patients.