Jean Paul Nshizirungu1, Sanae Bennis1, Ihsane Mellouki2, Dafr-Allah Benajah3, Nada Lahmidani3, Hicham El Bouhaddoutti4, Karim Ibn Majdoub4, Sidi Adil Ibrahimi5, Sónia Pires Celeiro6,7, Marta Viana-Pereira6,7, Rui Manuel Reis6,7,8. 1. Biomedical and Translational Research Laboratory, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez, Morocco. 2. Faculty of Medicine and Pharmacy, Abdelmalek Essaadi University, Tangier, Morocco. 3. Department of Gastroenterology, Hassan II University Hospital, Fez, Morocco. 4. Department of Visceral Surgery, Hassan II University Hospital, Fez, Morocco. 5. Department of General Surgery, Hassan II University Hospital, Fez, Morocco. 6. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal. 7. ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal. 8. Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
Abstract
Aim: To investigate correlations between microsatellite instability (MSI) and the phenotype, clinicopathological features, and overall survival (OS) in Moroccan gastric cancer (GC) patients. We evaluated the mutation frequency of 22 MSI-target genes in MSI-positive tumors. Materials and Methods: MSI evaluation were performed for 97 gastric tumors by multiplex polymerase chain reaction (PCR) using a panel of five quasimonomorphic mononucleotide repeat markers (NR27, NR21, NR24, BAT25, and BAT26). The mutation profiles of 22 MSI-target genes were assessed by multiplex PCR and genotyping. Kaplan-Meier curves, the log-rank test, and the Cox proportional hazard regression model were used to conduct survival analyses. Results: Microsatellite stable (MSS) status was observed in 77/97 (79.4%) gastric cancer samples, MSI-Low in 7 (7.2%) samples, and MSI-High (MSI-H) in 13 (13.4%) cases. The MSI-H phenotype was significantly associated with older age (p = 0.004), tumor location (p < 0.001), and intestinal-type of Lauren classification (p < 0.001). Among the 22 MSI target genes analyzed, the most frequently altered genes were HSP110 (84.6%), EGFR (30.8%), BRCA2 (23.1%), MRE11 (23.1%), and MSH3 (23.1%). Multivariate analysis revealed the MSS phenotype (Hazard ratio, 0.23; 95% confidence interval, 0.7-7.4; p = 0.014) as an independent indicator of poor prognosis in our population. Conclusions: This study is the first analysis of MSI in Moroccan GC patients. MSI-H GCs have distinct clinicopathological features and an improved OS. We have identified candidate target genes altered in MSI-positive tumors with potential clinical implications. These findings can guide immunotherapy designed for Moroccan GC patients.
Aim: To investigate correlations between microsatellite instability (MSI) and the phenotype, clinicopathological features, and overall survival (OS) in Moroccan gastric cancer (GC) patients. We evaluated the mutation frequency of 22 MSI-target genes in MSI-positive tumors. Materials and Methods: MSI evaluation were performed for 97 gastric tumors by multiplex polymerase chain reaction (PCR) using a panel of five quasimonomorphic mononucleotide repeat markers (NR27, NR21, NR24, BAT25, and BAT26). The mutation profiles of 22 MSI-target genes were assessed by multiplex PCR and genotyping. Kaplan-Meier curves, the log-rank test, and the Cox proportional hazard regression model were used to conduct survival analyses. Results: Microsatellite stable (MSS) status was observed in 77/97 (79.4%) gastric cancer samples, MSI-Low in 7 (7.2%) samples, and MSI-High (MSI-H) in 13 (13.4%) cases. The MSI-H phenotype was significantly associated with older age (p = 0.004), tumor location (p < 0.001), and intestinal-type of Lauren classification (p < 0.001). Among the 22 MSI target genes analyzed, the most frequently altered genes were HSP110 (84.6%), EGFR (30.8%), BRCA2 (23.1%), MRE11 (23.1%), and MSH3 (23.1%). Multivariate analysis revealed the MSS phenotype (Hazard ratio, 0.23; 95% confidence interval, 0.7-7.4; p = 0.014) as an independent indicator of poor prognosis in our population. Conclusions: This study is the first analysis of MSI in Moroccan GC patients. MSI-H GCs have distinct clinicopathological features and an improved OS. We have identified candidate target genes altered in MSI-positive tumors with potential clinical implications. These findings can guide immunotherapy designed for Moroccan GC patients.
Authors: Jean Paul Nshizirungu; Sanae Bennis; Ihsane Mellouki; Mohammed Sekal; Dafr-Allah Benajah; Nada Lahmidani; Hicham El Bouhaddouti; Karim Ibn Majdoub; Sidi Adil Ibrahimi; Sónia Pires Celeiro; Marta Viana-Pereira; Fernanda Franco Munari; Guilherme Gomes Ribeiro; Vinicius Duval; Iara Santana; Rui Manuel Reis Journal: Dis Markers Date: 2021-07-28 Impact factor: 3.434