Implication of Gastric Cancer Molecular Genetic Markers in Surgical Practice

Abstract

Introduction: We have investigated aberrant methylation of genes CDH1, RASSF1A, MLH1, N33, DAPK, expression of genes hTERT, MMP7, MMP9, BIRC5 (survivin), PTGS2, and activity of telomerase of 106 gastric tumor samples obtained intra-operatively and 53 gastric tumor samples from the same group of patients obtained endoscopically before surgery. Biopsy specimens obtained from 50 patients with chronic calculous cholecystitis were used as a control group. Together with tissue samples obtained from different sites remote to tumors, a total of 727 samples have been studied. The selected parameters comprise a system of molecular markers that can be used in both diagnostics of gastric cancer and in dynamic monitoring of patients after surgery. Special attention was paid to the use of molecular markers for the diagnostics of malignant process in the material obtained endoscopically since the efficacy of morphological diagnostics in biopsies is compromised by intratumoral heterogeneity, which may prevent reliable identification of tumor cells in the sampling. Our data indicated that certain molecular genetic events provided more sensitive yet specific markers of the tumor. Conclusion: We demonstrated that molecular profiles detected in preoperative biopsies were confirmed by the material obtained intra-operatively. The use of endoscopic material facilitates gastric tumors pre-operative diagnostics, improving early detection of gastric cancer and potential effective treatment strategies.

Retracted: Transcription activation of microRNA‐25 by PEA3 augments progression of gastric cancer through suppressing SIK1

“…GC remains a heavy burden and a huge challenge to the modern society with limited effective treatments for patients at advanced stages. In the field of genetics, genetic markers and genetic molecular mechanisms accountable for the progression of GC have aroused wide concerns (Nemtsova et al, 2017;Raimondi et al, 2018;Xiao et al, 2020;Yin et al, 2020). In the present study, we reported a novel PEA3/miR-25/SIK1 axis which potentially plays crucial functions in GC progression with the possible involvement of the Wnt/β-catenin signaling pathway.…”

Clinical relevance of somatic mutations in main driver genes detected in gastric cancer patients by next-generation DNA sequencing

“…Loss of CDH1 expression appears after inactivation of both copies, where one allele can be mutant, and the second allele is inactivated by promotor methylation in approximately 50% of cases. We have previously demonstrated that CDH1 promoter methylation is associated with the diffuse Lauren type and locally advanced GC 13 . Other studies have shown the prognostic relevance of CDH1 mutations in diffuse GC, where the presence of somatic mutations in this gene was associated with a decrease in patient survival, regardless of the stage of the disease 14 .…”

Roles of E-cadherin and Noncoding RNAs in the Epithelial–mesenchymal Transition and Progression in Gastric Cancer

“…Hypermethylation of various genes in gastric tissues is currently associated with a higher risk of tumorigenesis. Hypermethylation of CDH1 and other genes was observed in nontumor mucosa samples from GC patients [54,55].…”