Reproduction of the Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG) Gastric Cancer Molecular Classifications and Their Association with Clinicopathological Characteristics and Overall Survival in Moroccan Patients

Abstract

Introduction. The Cancer Genome Atlas (TCGA) project and Asian Cancer Research Group (ACRG) recently categorized gastric cancer into molecular subtypes. Nevertheless, these classification systems require high cost and sophisticated molecular technologies, preventing their widespread use in the clinic. This study is aimed to generating molecular subtypes of gastric cancer using techniques available in routine diagnostic practice in a series of Moroccan gastric cancer patients. In addition, we assessed the associations between molecular subtypes, clinicopathological features, and prognosis. Methods. Ninety-seven gastric cancer cases were classified according to TCGA, ACRG, and integrated classifications using a panel of four molecular markers (EBV, MSI, E-cadherin, and p53). HER2 status and PD-L1 expression were also evaluated. These markers were analyzed using immunohistochemistry (E-cadherin, p53, HER2, and PD-L1), in situ hybridization (EBV and HER2 equivocal cases), and multiplex PCR (MSI). Results. Our results showed that the subtypes presented distinct clinicopathological features and prognosis. EBV-positive gastric cancers were found exclusively in male patients. The GS (TCGA classification), MSS/EMT (ACRG classification), and E-cadherin aberrant subtype (integrated classification) presented the Lauren diffuse histology enrichment and tended to be diagnosed at a younger age. The MSI subtype was associated with a better overall survival across all classifications (TCGA, ACRG, and integrated classification). The worst prognosis was observed in the EBV subtype (TCGA and integrated classification) and MSS/EMT subtype (ACRG classification). Discussion/Conclusion. We reported a reproducible and affordable gastric cancer subtyping algorithms that can reproduce the recently recognized TCGA, ACRG, and integrated gastric cancer classifications, using techniques available in routine diagnosis. These simplified classifications can be employed not only for molecular classification but also in predicting the prognosis of gastric cancer patients.

Immunohistochemical Markers of the Epithelial-to-Mesenchymal Transition (EMT) Are Related to Extensive Lymph Nodal Spread, Peritoneal Dissemination, and Poor Prognosis in the Microsatellite-Stable Diffuse Histotype of Gastric Cancer

“…In the ACRG study, more than 80% of the EMT cases were diffuse, but less than 50% of the diffuse-type cases belonged to the EMT subgroup [ 9 ]. The percentage of diffuse-type cases showing an EMT phenotype in our series (54%) was like the rate found in the ACRG study, as well as other reports [ 9 , 20 , 29 ]. In several studies, the Lauren classification was not used, and this did not allow a comparison with the present series [ 12 , 15 ].…”

“…Some reports have suggested that the EMT phenotype is correlated with younger age, diffuse/poorly differentiated histology, advanced TNM stage, and worse prognosis of GC [ 9 , 11 , 12 , 15 , 16 , 26 , 27 , 28 , 29 ]. The strong association with the diffuse histotype or undifferentiated histology may act as a confounding factor, and it is unclear if this association could explain the clinical behavior of EMT-positive tumors [ 9 , 12 , 28 , 29 ]. For this reason, we focused our analysis on MSS diffuse-type tumors.…”

Genomic analysis of matrix metalloproteinases affecting the prognosis and immunogenic profile of gastric cancer

“…We selected four datasets (GSE26901、GSE13861、GSE26899、GSE66229) about gene expression profiles of GC from GEO for the validation group. (GSE26901 from the Kosin University College of Medicine, GSE13861 from the Yonsei University Severance Hospital, GSE26899 from the Korea University Guro Hospital, and GSE66229 from the Asian Cancer Research Group) ( Cho et al, 2011 ; Oh et al, 2018 ; Nshizirungu et al, 2021 ).…”

Molecular Classifications in Gastric Cancer: A Call for Interdisciplinary Collaboration

“…As mentioned earlier, the most significant molecular systems published in GC are those of TCGA and the ACRG, which have been extensively analyzed in previous studies [ 74 , 149 , 150 , 151 , 152 , 153 , 154 ]. Nevertheless, various alternative classifications have emerged, either utilizing independent cohorts or drawing from existing databases, such as those of TCGA, the ACRG, or the Gene Expression Omnibus (GEO) repository.…”