The goal of this work was to investigate the molecular profiles and metastasis markers in Chinese patients with gastric carcinoma (GC). In total, we performed whole exome sequencing (WES) on 74 GC patients with tumor and adjacent normal formalin-fixed, paraffin-embedded (FFPE) tissue samples. The mutation spectrum of these samples showed a high concordance with TCGA and other studies on GC. PTPRT is significantly associated with metastasis of GC, suggesting its predictive role in metastasis of GC. Patients carrying BRCA2 mutations tend not to metastasize, which may be related to their sensitivity to chemotherapy. Mutations in MACF1, CDC27, HMCN1, CDH1 and PDZD2 were moderately enriched in peritoneal metastasis (PM) samples. Furthermore, we found two genomic regions (1p36.21 and Xq26.3) were associated with PM of GC, and patients with amplification of 1p36.21 and Xq26.3 have a worse prognosis (P = 0.002, 0.01, respectively). Our analysis provides GC patients with potential markers for single and combination therapies.
Immunotherapy directed against cancer-specific neoantigens derived from non-silent mutants is a promising individualized strategy for cancer treatment. Neoantigens shared across patients could be used as a public resource for developing T cell-based therapy. To identify potential public neoantigens for therapy in gastric cancer (GC), 74 GC patients were enrolled in this study. Combined with the TCGA cohort and other published studies, whole exome sequencing data from 942 GC patients were used to detect somatic mutations and predict neoantigens shared by GC patients. The mutations pattern between our study and the TCGA cohort is comparable, and C > T is the most common substitution. The number of neoantigens was significantly higher in older patients (age ≥60) compared to younger patients (age <60), both in this study and the TCGA cohort. Recurrent neoantigens were found in eight genes (TP53, PIK3CA, PGM5, ERBB3, C6, TRIM49C, OR4C16, and KRAS) in this study. The neoantigen-associated mutations PIK3CA (p.H1047R) and TP53 (p.R175H) are common across several cancer types, indicating their potential usage. Overall, our study illustrates a comprehensive genomic landscape of GC and provides the recurrent neoantigens to facilitate further immunotherapy.
Protein expression of vascular endothelial growth factor A (VEGF-A) and matrix metalloproteinase 9 (MMP-9) was studied in gastric carcinoma patients in relation to clinicopathological characteristics and prognosis. Fifty-four samples of gastric carcinoma tissue and 15 samples of adjacent normal gastric mucosal tissue were examined immunohistochemically. Expression rates of VEGF-A (66.7%) and MMP-9 (63.0%) in carcinoma tissue were significantly higher than in normal tissue (6.7% for both proteins). VEGF-A and MMP9 expression was associated with tumour size, invasion depth, lymph node metastasis, degree of histological differentiation and pathological stage, but not age or sex. VEGF-A expression was positively correlated with that of MMP-9. Expression of VEGF-A and MMP-9 were each inversely correlated with 5-year survival. VEGF-A and MMP-9 were overexpressed in tumours compared with normal tissue; they may act together to increase carcinogenesis and the progression, invasion and metastasis of gastric carcinoma, and could be used as biomarkers for the prognosis of gastric carcinoma.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.