Y Yang1, Y Q Liu2, X H Wang3, K Ji1, Z W Li2, J Bai4, A R Yang4, Y Hu3, H B Han3, Z Y Li1, Z D Bu1, X J Wu1, L H Zhang1, J F Ji1. 1. Department of Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education; Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing 100142, China. 2. Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education; Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing 100142, China. 3. Department of Biobank, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education; Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing 100142, China. 4. Berry Oncology Corporation, Beijing 102206, China.
Abstract
OBJECTIVE: Epstein-Barr virus associated gastric cancer (EBVaGC) is different from the traditional gastric cancer (Epstein-Barr virus non-associated gastric cancer, EBVnGC), and has unique clinicopathological features. This study investigated the largest single center cancer series so as to establish the clinicopathological and molecular characteristics of EBVaGC in China. METHODS: A retrospective analysis was conducted on EBVaGC and EBVnGC patients diagnosed at Peking University Cancer Hospital from 2003 to 2018 by comparing their clinicopathological features and prognosis. The gastric cancer (GC) dataset of public database was analyzed to obtain differentially expressed genes. The expression of important genes and their association with prognosis of GC were verified in GC tissues from our hospital. RESULTS: In this study, 3 241 GC patients were included, and a total of 163 EBVaGC (5.0%) patients were identified. Compared with EBVnGC, EBVaGC was higher in male and younger patients, and positively associated with remnant GC, poorly differentiated adenocarcinoma, and mixed type GC. EBVaGC was inversely related to lymph node metastasis. The 5-year survival rate of EBVnGC and EBVaGC was 59.6% and 63.2% respectively (P<0.05). In order to explore molecular features of EBVaGC, the Cancer Genome Atlas (TCGA) dataset was analyzed (n=240), and 7 404 significant differentially expressed genes were obtained, involving cell proliferation, apoptosis, invasion and metastasis. The down-regulated invasion/metastasis gene SALL4 and the up-regulated immune checkpoint gene PD-L1 were important molecular features of EBVaGC. Validation of these two genes in large GC series showed that the majority of the EBVaGC was SALL4 negative (1/92, 1.1%, lower than EBVnGC, 303/1 727, 17.5%), and that PD-L1 was mostly positive in EBVaGC (81/110, 73.6%, higher than EBVnGC, 649/2 350, 27.6%). GC patients with SALL4 negative and PD-L1 positive were often associated with better prognosis. CONCLUSION: EBVaGC is a unique subtype of GC with less metastasis and a good prognosis. It also has a distinct molecular background. The down-regulation of invasion/metastasis gene SALL4 and up-regulation of immune checkpoint gene PD-L1 are important molecular features.
OBJECTIVE:Epstein-Barr virus associated gastric cancer (EBVaGC) is different from the traditional gastric cancer (Epstein-Barr virus non-associated gastric cancer, EBVnGC), and has unique clinicopathological features. This study investigated the largest single center cancer series so as to establish the clinicopathological and molecular characteristics of EBVaGC in China. METHODS: A retrospective analysis was conducted on EBVaGC and EBVnGC patients diagnosed at Peking University Cancer Hospital from 2003 to 2018 by comparing their clinicopathological features and prognosis. The gastric cancer (GC) dataset of public database was analyzed to obtain differentially expressed genes. The expression of important genes and their association with prognosis of GC were verified in GC tissues from our hospital. RESULTS: In this study, 3 241 GC patients were included, and a total of 163 EBVaGC (5.0%) patients were identified. Compared with EBVnGC, EBVaGC was higher in male and younger patients, and positively associated with remnant GC, poorly differentiated adenocarcinoma, and mixed type GC. EBVaGC was inversely related to lymph node metastasis. The 5-year survival rate of EBVnGC and EBVaGC was 59.6% and 63.2% respectively (P<0.05). In order to explore molecular features of EBVaGC, the Cancer Genome Atlas (TCGA) dataset was analyzed (n=240), and 7 404 significant differentially expressed genes were obtained, involving cell proliferation, apoptosis, invasion and metastasis. The down-regulated invasion/metastasis gene SALL4 and the up-regulated immune checkpoint gene PD-L1 were important molecular features of EBVaGC. Validation of these two genes in large GC series showed that the majority of the EBVaGC was SALL4 negative (1/92, 1.1%, lower than EBVnGC, 303/1 727, 17.5%), and that PD-L1 was mostly positive in EBVaGC (81/110, 73.6%, higher than EBVnGC, 649/2 350, 27.6%). GC patients with SALL4 negative and PD-L1 positive were often associated with better prognosis. CONCLUSION:EBVaGC is a unique subtype of GC with less metastasis and a good prognosis. It also has a distinct molecular background. The down-regulation of invasion/metastasis gene SALL4 and up-regulation of immune checkpoint gene PD-L1 are important molecular features.
Authors: L Zhang; Z Xu; X Xu; B Zhang; H Wu; M Wang; X Zhang; T Yang; J Cai; Y Yan; F Mao; W Zhu; Q Shao; H Qian; W Xu Journal: Oncogene Date: 2013-11-25 Impact factor: 9.867
Authors: Kol Jia Yong; Chong Gao; Joline S J Lim; Benedict Yan; Henry Yang; Todor Dimitrov; Akira Kawasaki; Chee Wee Ong; Kwong-Fai Wong; Sanghoon Lee; Sharada Ravikumar; Supriya Srivastava; Xi Tian; Ronnie T Poon; Sheung Tat Fan; John M Luk; Yock Young Dan; Manuel Salto-Tellez; Li Chai; Daniel G Tenen Journal: N Engl J Med Date: 2013-06-13 Impact factor: 91.245
Authors: Dong Won Baek; Byung Woog Kang; Soyoon Hwang; Jong Gwang Kim; An Na Seo; Han Ik Bae; Oh Kyoung Kwon; Seung Soo Lee; Ho Young Chung; Wansik Yu Journal: Chonnam Med J Date: 2017-05-25