Clinical characteristics and prognostic significance of TCGA and ACRG classification in gastric cancer among the Chinese population

Abstract

Molecular classifications of gastric cancer (GC) by the Asian Cancer Research Group (ACRG) and The Cancer Genome Atlas Consortium (TCGA) are useful for diagnosis and treatment of GC. However, their clinical significance is unknown. The present study aims to explore the associations between subtypes of GC and prognosis of patients with GC. Immunohistochemistry (IHC) was used in the ACRG molecular classification of GC, while next‑generation sequencing technology was used in TCGA molecular classification. The results indicated that, out of a total of 65 cases of GC, some were classified as Epstein‑Barr virus positive type (9.2%, 6 of 65), some as microsatellite instability (MSI) type (23.1%, 15 of 65), some as gene stable type (21.5%, 14 of 65) and some as chromosome instability type (46.2%, 30 of 65) according to TCGA typing standard. Of the total 65 GC cases, some were classified as MSI (21.5%, 14 of 65), some as microsatellite stable/epithelial‑mesenchymal transition (MSS/EMT; 20.0%, 13 of 65), some as MSS/tumor protein 53 active (TP53+; 15.4%, 10 of 65) and some as MSS/TP53 inactive (43.1%, 28 of 65) according to ACRG typing standard. ARCG molecular subtype (P=0.010) and Lauren classification (P=0.011) were independently correlated with the overall survival of patients with GC. In conclusion, TCGA classification based on a Chinese population is the same as TCGA typing based on a European population in terms of proportion and clinical characteristics, but there are differences in gene amplification and gene mutation. ACRG molecular classification could be performed by IHC analysis and may be a valuable independent prognostic marker for patients with GC.

Keywords: gastric cancer; Asian Cancer Research Group; The Cancer Genome Atlas Consortium; next‑generation sequencing; immunohistochemical staining; prognosis.

Figure 1.

TCGA molecular classification of GC. (A) Flow diagram illustrating how GC divided according to TCGA molecular classification. (B) Differences in gender among subtypes. (C) Differences in age among classification. (D) Differences in tumor location among classification. TCGA, The Cancer Genome Atlas; GC, gastric cancer; EBV, Epstein-Barr virus; MSI, microsatellite instability; GS, gene stable; CIN, chromosome instability; EGJ, gastro-esophageal junction.

Figure 2.

Significantly mutated and amplified genes in gastric cancer. (A) Mutated genes. (B) Amplified genes.

Figure 3.

Heat map for the mutated and amplified genes. EBV, Epstein-Barr virus; MSI, microsatellite instability; GS, gene stable; CIN, chromosome instability.

Figure 4.

Multiple markers expression in gastric cancer by immunohistochemistry staining. (A) MLH1 positive staining. (B) MLH1 negative staining. (C) E-cadherin positive staining, (D) E-cadherin negative staining. (E) Vimentin positive staining. (F) Vimentin negative staining. (G) MDM2 positive staining. (H) MDM2 negative staining. (I) P21 positive staining and (J) P21 negative staining. Magnification (a), ×200; (b), ×400. MLH1, MutL protein homolog 1; MDM2, mouse double minute 2 homolog; P21, cyclin-dependent kinase inhibitor 1A.

Figure 5.

ACRG molecular classification of GC. (A) Flow diagram illustrating how GC divided according to ACRG molecular classification. (B) Differences in tumor location among subtypes. (C) Differences in Lauren classification among subtypes. ACRG, Asian Cancer Research Group; GC, gastric cancer; MSI, microsatellite instability; MSS, microsatellite stable; EMT, epithelial-mesenchymal transition; TP53, tumor protein 53; EGJ, gastro-esophageal junction.

Figure 6.

Kaplan-Meier curves for the overall survival of 65 patients with gastric cancer. (A) Lauren classification, (B) postoperative adjuvant chemotherapy, (C) ACRG molecular subtypes, (D) TCGA molecular subtypes, (E) Polygenic mutation and (F) Polygenic amplification. XELOX, capecitabine combined with oxaliplatin; SOX, S1 combined with oxaliplatin; MSI, microsatellite instability; MSS, microsatellite stable; EMT, epithelial-mesenchymal transition; TP53, tumor protein 53; EBV, Epstein-Barr virus; MSI, microsatellite instability; GS, gene stable; CIN, chromosome instability.