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Mazurek M, Jaros M, Gliwa AM, Sitarz MZ, Dudzińska E, Zinkiewicz K, Sitarz R. Epstein-Barr Virus (EBV) and Human Papilloma Virus (HPV) in Gastric Cancers, with Special Reference to Gastric Cancer at a Young Age-A Pilot Study in Poland. Int J Mol Sci 2025; 26:711. [PMID: 39859425 PMCID: PMC11765604 DOI: 10.3390/ijms26020711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 01/06/2025] [Accepted: 01/07/2025] [Indexed: 01/27/2025] Open
Abstract
Gastric cancer (GC) is one of the most common cancers in the world. It is a multi-factorial disease influenced by both genetic and environmental factors such as diet, obesity, radiation exposure, and infectious agents. Viral infections usually lead to chronic inflammation, which can initiate the development of cancers. To date, only a few studies have been published about Epstein-Barr virus (EBV) and human papillomavirus (HPV) infections in the context of the development of GC. In particular, research on the development of cancer among people under 45 years of age, including the impacts of EBV and HPV, is rare, and clear results have not been obtained. The aim of this study was to analyze the frequency of occurrence of EBV and HPV in GC, particularly in early-onset gastric cancer (EOGC). Tissue material from 135 patients with GC, including 84 men and 51 women, was examined. RT-PCR was performed to detect EBV, and PCR was performed to detect HPV. There were no significant impacts of EBV and HPV infections on any subtype of GC. There was also no statistically significant dependence of gender and location of the tumor on any subtype of GC. Further research on the impacts of infectious agents such as EBV and HPV on GC should be conducted using larger populations.
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Affiliation(s)
- Marek Mazurek
- Department of Surgical Oncology, Masovian Cancer Hospital, 05-135 Wieliszew, Poland;
- Department of Normal, Clinical and Imaging Anatomy, Medical University of Lublin, 20-950 Lublin, Poland; (M.J.); (A.M.G.)
| | - Małgorzata Jaros
- Department of Normal, Clinical and Imaging Anatomy, Medical University of Lublin, 20-950 Lublin, Poland; (M.J.); (A.M.G.)
| | - Anna M. Gliwa
- Department of Normal, Clinical and Imaging Anatomy, Medical University of Lublin, 20-950 Lublin, Poland; (M.J.); (A.M.G.)
| | - Monika Z. Sitarz
- Department of Conservative Dentistry with Endodontics, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Ewa Dudzińska
- Department of Dietetics and Nutrition Education, Medical University of Lublin, 20-093 Lublin, Poland;
| | - Krzysztof Zinkiewicz
- Independent Laboratory of Diagnostic, Interventional Endoscopy of the Department of Oncology, Medical University of Lublin, 20-081 Lublin, Poland;
| | - Robert Sitarz
- Department of Normal, Clinical and Imaging Anatomy, Medical University of Lublin, 20-950 Lublin, Poland; (M.J.); (A.M.G.)
- Department of Surgical Oncology, St. John’s Cancer Center, 20-090 Lublin, Poland
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Dokanei S, Minai‐Tehrani D, Moghoofei M, Rostamian M. Investigating the relationship between Epstein-Barr virus infection and gastric cancer: A systematic review and meta-analysis. Health Sci Rep 2024; 7:e1976. [PMID: 38505684 PMCID: PMC10948593 DOI: 10.1002/hsr2.1976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 02/06/2024] [Accepted: 02/28/2024] [Indexed: 03/21/2024] Open
Abstract
Background and Aims Gastric cancer (GC) is a common cancer type worldwide, and various factors can be involved in its occurrence. One of these factors is Epstein-Barr virus (EBV) infection. In this regard, a systematic review and meta-analysis was conducted to achieve a better understanding of the EBV prevalence in GC samples. Methods English databases were searched and studies that reported the prevalence and etiological factors of EBV related to GC from July 2007 to November 2022 were retrieved. The reported data were selected based on the inclusion and exclusion criteria. The pooled prevalence of EBV infection with 95% confidence intervals was calculated. Quality assessment, heterogeneity testing, and publication bias assessment were also performed. The literature search showed 953 studies, of which 87 studies met our inclusion criteria and were used for meta-analysis. Results The pooled prevalence of EBV infection related to GC was estimated to be 9.5% (95% confidence interval [CI]: 8.2%-11%) in the general population. The prevalence of EBV infection related to GC by gender was 13.5% (95% CI: 11.1%-16.3%) in males and 7.6% (95% CI: 5.4%-10.6%) in females. No significant differences were observed in terms of geographical region. Out of the 87 studies included in the meta-analysis, the most common diagnostic test was in situ hybridization (58 cases). Conclusions Altogether, the results indicated that EBV infection is one of the important factors in the development of GC. However, this does not necessarily mean that EBV infection directly causes GC since other factors may also be involved in the development of GC. Therefore, it is recommended to conduct extensive epidemiological studies on various aspects of the relationship between this virus and GC, which can provide valuable information for understanding the relationship between EBV and GC.
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Affiliation(s)
- Saman Dokanei
- Faculty of Life Sciences and BiotechnologyShahid Beheshti University (GC)TehranIran
| | | | - Mohsen Moghoofei
- Department of Microbiology, Faculty of MedicineKermanshah University of Medical SciencesKermanshahIran
| | - Mosayeb Rostamian
- Infectious Diseases Research Center, Health InstituteKermanshah University of Medical SciencesKermanshahIran
- Student Research CommitteeKermanshah University of Medical SciencesKermanshahIran
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Kim JH, Kim N, Song DH, Choi Y, Jeon EB, Kim S, Jun YK, Yoon H, Shin CM, Park YS, Lee DH, Oh HJ, Lee HS, Park YS, Ahn SH, Suh YS, Park DJ, Kim HH, Kim JW, Kim JW, Lee KW, Chang W, Park JH, Lee YJ, Lee KH, Kim YH, Ahn S. Sex-dependent different clinicopathological characterization of Epstein-Barr virus-associated gastric carcinoma: a large-scale study. Gastric Cancer 2024; 27:221-234. [PMID: 38212543 PMCID: PMC10896815 DOI: 10.1007/s10120-023-01460-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 12/16/2023] [Indexed: 01/13/2024]
Abstract
BACKGROUND Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) has been reported to account for approximately 5-16% of all GCs with good prognosis compared to EBV-negative GC. We evaluated the clinicopathological characteristics of EBVaGC including survival rate in South Korea. METHODS A total of 4,587 patients with GC who underwent EBV in situ hybridization (EBV-ISH) were prospectively enrolled at the Seoul National University Bundang Hospital from 2003 to 2021. Age, sex, smoking status, cancer type and stage, tumor size and location, histological type, molecular features and survival information were analyzed. RESULTS A total of 456 patients with GC (9.9%) were positive for EBV. The EBVaGC group displayed a higher proportion of males (P < 0.001), a predominant presence in the proximal stomach (P < 0.001), a higher proportion of undifferentiated cancer (P < 0.001), and a lower cancer stage (P = 0.004) than the EBV-negative group. Cox multivariate analyses revealed age (hazard ratio [HR] = 1.025, P < 0.001), tumor size (HR = 1.109, P < 0.001), and cancer stage (stage2 HR = 4.761, P < 0.001; stage3 HR = 13.286, P < 0.001; stage4 HR = 42.528, P < 0.001) as significant risk factors for GC-specific mortality, whereas EBV positivity was inversely correlated (HR = 0.620, P = 0.022). Furthermore, the EBVaGC group displayed statistically significant survival advantages over the EBV-negative cancer group in terms of both overall (P = 0.021) and GC-specific survival (P = 0.007) on the Kaplan-Meier survival curve. However, this effect was evident only in males. CONCLUSIONS EBVaGC patients showed better prognoses despite their association with proximal location and poorly differentiated histology in male, probably due to the difference in immunity between males and females.
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Affiliation(s)
- Ji-Hyun Kim
- Departments of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam, Gyeonggi-Do, 13620, South Korea
| | - Nayoung Kim
- Departments of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam, Gyeonggi-Do, 13620, South Korea.
- Departments of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
| | - Du Hyun Song
- Departments of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam, Gyeonggi-Do, 13620, South Korea
| | - Yonghoon Choi
- Departments of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam, Gyeonggi-Do, 13620, South Korea
| | - Eun-Bi Jeon
- Departments of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam, Gyeonggi-Do, 13620, South Korea
| | - Sihyun Kim
- Departments of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam, Gyeonggi-Do, 13620, South Korea
| | - Yu Kyung Jun
- Departments of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam, Gyeonggi-Do, 13620, South Korea
| | - Hyuk Yoon
- Departments of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam, Gyeonggi-Do, 13620, South Korea
| | - Cheol Min Shin
- Departments of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam, Gyeonggi-Do, 13620, South Korea
| | - Young Soo Park
- Departments of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam, Gyeonggi-Do, 13620, South Korea
| | - Dong Ho Lee
- Departments of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam, Gyeonggi-Do, 13620, South Korea
- Departments of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
| | - Hyeon Jeong Oh
- Departments of Pathology, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Hye Seung Lee
- Departments of Pathology, Seoul National University College of Medicine, Seoul, South Korea
| | - Young Suk Park
- Departments of Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Sang-Hoon Ahn
- Departments of Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Yun-Suhk Suh
- Departments of Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Do Joong Park
- Departments of Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea
- Departments of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Hyung Ho Kim
- Departments of Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea
- Departments of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Ji-Won Kim
- Departments of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam, Gyeonggi-Do, 13620, South Korea
| | - Jin Won Kim
- Departments of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam, Gyeonggi-Do, 13620, South Korea
| | - Keun-Wook Lee
- Departments of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam, Gyeonggi-Do, 13620, South Korea
- Departments of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
| | - Won Chang
- Departments of Radiology, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Ji Hoon Park
- Departments of Radiology, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Yoon Jin Lee
- Departments of Radiology, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Kyoung Ho Lee
- Departments of Radiology, Seoul National University Bundang Hospital, Seongnam, South Korea
- Departments of Radiology, Seoul National University College of Medicine, Seoul, South Korea
| | - Young Hoon Kim
- Departments of Radiology, Seoul National University Bundang Hospital, Seongnam, South Korea
- Departments of Radiology, Seoul National University College of Medicine, Seoul, South Korea
| | - Soyeon Ahn
- Division of Statistics, Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, South Korea
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Low YH, Loh CJL, Peh DYY, Chu AJM, Han S, Toh HC. Pathogenesis and therapeutic implications of EBV-associated epithelial cancers. Front Oncol 2023; 13:1202117. [PMID: 37901329 PMCID: PMC10600384 DOI: 10.3389/fonc.2023.1202117] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Accepted: 09/07/2023] [Indexed: 10/31/2023] Open
Abstract
Epstein-Barr virus (EBV), one of the most common human viruses, has been associated with both lymphoid and epithelial cancers. Undifferentiated nasopharyngeal carcinoma (NPC), EBV associated gastric cancer (EBVaGC) and lymphoepithelioma-like carcinoma (LELC) are amongst the few common epithelial cancers that EBV has been associated with. The pathogenesis of EBV-associated NPC has been well described, however, the same cannot be said for primary pulmonary LELC (PPLELC) owing to the rarity of the cancer. In this review, we outline the pathogenesis of EBV-associated NPC and EBVaGCs and their recent advances. By drawing on similarities between NPC and PPLELC, we then also postulated the pathogenesis of PPLELC. A deeper understanding about the pathogenesis of EBV enables us to postulate the pathogenesis of other EBV associated cancers such as PPLELC.
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Affiliation(s)
- Yi Hua Low
- Duke-NUS Medical School, Singapore, Singapore
| | | | - Daniel Yang Yao Peh
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Axel Jun Ming Chu
- Singapore Health Services Internal Medicine Residency Programme, Singapore, Singapore
| | - Shuting Han
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Han Chong Toh
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
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Vidal-Realpe A, Dueñas-Cuellar RA, Niño-Castaño VE, Mora-Obando DL, Arias-Agudelo JJ, Bolaños HJ. Clinical and pathologic characteristics of gastric adenocarcinoma associated with Epstein-Barr virus in a region with a high incidence of gastric cancer in Colombia. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2023; 88:256-266. [PMID: 35810098 DOI: 10.1016/j.rgmxen.2021.10.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 10/18/2021] [Indexed: 02/07/2023]
Abstract
INTRODUCTION AND AIMS Epstein-Barr virus (EBV) infection is an etiologic factor in EBV-associated gastric carcinoma (EBVaGC). The aim of our study was to describe the clinical and histopathologic characteristics of EBV infection in intestinal-type gastric adenocarcinoma samples. MATERIAL AND METHODS Of 180 paraffin-embedded gastrectomy samples, 28 were studied. Chromogenic in situ hybridization was performed to detect EBV. Sociodemographic and histopathologic data were obtained from the patients' clinical histories. RESULTS A total of 21.4% of the samples were positive for EBV. The predominant morphologic characteristic was the lace pattern, with dense inflammatory infiltration. Fifty percent of the EBVaGC+ patients were men, and the median age of the positive patients was 59 years (range: 50-75); 77.2% of the EBVaGC- patients were men, and the median age of the negative patients was 66 years (range: 34-89). Helicobacter pylori infection was associated with 10.7% of the EBVaGC+ patients and 53.6% of the EBVaGC- patients. In the EBVaGC+ patients, the cardia was the most frequent tumor location (17.9%), 7.1% had histologic grades 2 and 3, and 17.9% presented with Borrmann classification type III. In the EBVaGC- patients, the cardia and fundus were the most frequent tumor locations (71.4%), 35.7% had histologic grade 2, and 39.3% and 21.4% presented with Borrmann classification type III and IV, respectively. CONCLUSIONS The present study describes the clinical and histopathologic characteristics associated with EBVaGC positivity. Those data may aid in the selection of cases that are candidates for analysis through molecular methods aimed at identifying EBV infection in intestinal-type gastric adenocarcinoma.
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Affiliation(s)
- A Vidal-Realpe
- Programa de Medicina, Grupo de Investigación en Inmunología y Enfermedades Infecciosas, Facultad de Ciencias de la Salud, Universidad del Cauca, Popayán, Cauca, Colombia
| | - R A Dueñas-Cuellar
- Departamento de Patología, Grupo de Investigación en Inmunología y Enfermedades Infecciosas, Facultad de Ciencias de la Salud, Universidad del Cauca, Popayán, Cauca, Colombia
| | - V E Niño-Castaño
- Departamento de Patología, Grupo de Investigación en Inmunología y Enfermedades Infecciosas, Facultad de Ciencias de la Salud, Universidad del Cauca, Popayán, Cauca, Colombia
| | - D L Mora-Obando
- Grupo de Investigación en Inmunología y Enfermedades Infecciosas, Facultad de Ciencias de la Salud, Universidad del Cauca, Popayán, Cauca, Colombia
| | - J J Arias-Agudelo
- Médico Especialista en Patología Anatómica y Clínica, Bogotá, Colombia
| | - H J Bolaños
- Departamento de Patología, Grupo de Investigación en Inmunología y Enfermedades Infecciosas, Facultad de Ciencias de la Salud, Universidad del Cauca, Popayán, Cauca, Colombia.
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Xie C, Zhong LY, Bu GL, Zhao GX, Yuan BY, Liu YT, Sun C, Zeng MS. Anti-EBV antibodies: Roles in diagnosis, pathogenesis, and antiviral therapy. J Med Virol 2023; 95:e28793. [PMID: 37212266 DOI: 10.1002/jmv.28793] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 05/02/2023] [Accepted: 05/03/2023] [Indexed: 05/23/2023]
Abstract
Epstein-Barr virus (EBV) infection is prevalent in global population and associated with multiple malignancies and autoimmune diseases. During the infection, EBV-harbored or infected cell-expressing antigen could elicit a variety of antibodies with significant role in viral host response and pathogenesis. These antibodies have been extensively evaluated and found to be valuable in predicting disease diagnosis and prognosis, exploring disease mechanisms, and developing antiviral agents. In this review, we discuss the versatile roles of EBV antibodies as important biomarkers for EBV-related diseases, potential driving factors of autoimmunity, and promising therapeutic agents for viral infection and pathogenesis.
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Affiliation(s)
- Chu Xie
- State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China
| | - Lan-Yi Zhong
- State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China
| | - Guo-Long Bu
- State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China
| | - Ge-Xin Zhao
- State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China
| | - Bo-Yu Yuan
- State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China
| | - Yuan-Tao Liu
- State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China
| | - Cong Sun
- State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China
| | - Mu-Sheng Zeng
- State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China
- Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Guangzhou, China
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Li G, Zhou Z, Wang Z, Wang Z. Assessing Epstein-Barr virus in gastric cancer: clinicopathological features and prognostic implications. Infect Agent Cancer 2023; 18:11. [PMID: 36803802 PMCID: PMC9938970 DOI: 10.1186/s13027-023-00489-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Accepted: 02/14/2023] [Indexed: 02/21/2023] Open
Abstract
BACKGROUND Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) was a unique molecular subtype of gastric cancer (GC). However, the clinicopathological characteristics and prognostic role of EBV infection remains unclear. We aimed to evaluate the clinicopathological features of EBVaGC and its role on prognosis. METHODS EBV-encoded RNA (EBER) in situ hybridization method was used to evaluate the EBV status in GC. The serum tumor markers AFP, CEA, CA19-9 and CA125 of patients were detected before treatment. HER2 expression and microsatellite instability (MSI) status was evaluated according to established criteria. The relationship between EBV infection and clinicopathological factors as well as its role on prognosis were investigated. RESULTS 420 patients were enrolled in the study and of 53 patients (12.62%) were identified as EBVaGC. EBVaGC was more common in males (p = 0.001) and related to early T stage (p = 0.045), early TNM stage (p = 0.001) and lower level of serum CEA (p = 0.039). No association could be found between EBV infection and HER2 expression, MSI status and other factors (p all > 0.05). Kaplan-Meier analysis revealed that both the overall survival and disease-free survival of EBVaGC patients were similar to that of EBV-negative GC (EBVnGC) patients (p = 0.309 and p = 0.264, respectively). CONCLUSION EBVaGC was more common in males and in patients with the early T stage and TNM stage as well as patients with lower serum CEA level. Difference in overall survival and disease-free survival between EBVaGC and EBVnGC patients cannot be detected.
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Affiliation(s)
- Guanghua Li
- grid.412615.50000 0004 1803 6239Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Zhongshan 2nd Street, No. 58, Guangzhou, 510080 Guangdong China
| | - Zhihao Zhou
- grid.412615.50000 0004 1803 6239Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Zhongshan 2nd Street, No. 58, Guangzhou, 510080 Guangdong China
| | - Zhixiong Wang
- grid.412615.50000 0004 1803 6239Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Zhongshan 2nd Street, No. 58, Guangzhou, 510080 Guangdong China
| | - Zhao Wang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Zhongshan 2nd Street, No. 58, Guangzhou, 510080, Guangdong, China.
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Kinases and therapeutics in pathogen mediated gastric cancer. Mol Biol Rep 2022; 49:2519-2530. [PMID: 35031925 DOI: 10.1007/s11033-021-07063-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 12/08/2021] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Many pathogens have coexisted with humans for millennia and can cause chronic inflammation which is the cause of gastritis. Gastric cancer (GC) is associated with 8.8% of cancer related deaths, making it one of the leading causes of cancer related deaths worldwide. This review is intended to give brief information about Helicobacter pylori (H. pylori), Epstein-Barr virus (EBV), human cytomegalovirus (HCMV) role in GC and associated kinases. These organisms can trigger multiple cellular pathways aiming for unnatural cellular proliferation, apoptosis, migration and inflammatory response. Kinases also can activate and deactivate the signalling leading to aforementioned pathways. Therefore, studying kinases is inevitable. MATERIAL AND METHODS This review is the comprehensive collection of information from different data sources such as journals, book, book chapters and verified online information. CONCLUSION Kinase amplifications could be used as diagnostic, prognostic, and predictive biomarkers in various cancer types. Hence targeting kinase and related signalling molecules could be considered as a potential approach to prevent cancer through these organisms. Here we summarize the brief information about the role of kinases, signalling and their therapeutics in GC concerning H. pylori, EBV and HCMV.
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Manuel Lopes de Sousa H, Patrícia Costa Ribeiro J, Basílio Timóteo M. Epstein-Barr Virus-Associated Gastric Cancer: Old Entity with New Relevance. Infect Dis (Lond) 2021. [DOI: 10.5772/intechopen.93649] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Gastric cancer (GC) represents a major public health issue worldwide, being the fifth most common cancer and one of the leading causes of death by cancer. In 2014, The Cancer Genome Atlas (TCGA) established that tumors positive for Epstein-Barr virus (EBV) are considered a specific subtype of GC (EBVaGC). Several meta-analyses have shown that EBVaGC represents almost 10% of all gastric cancer worldwide, with small differences in the geographic distribution. This tumor subtype has a high potential of being clinically relevant and studies have shown that it has specific features, a better prognosis, and increased overall survival. In this review, we summarize some of the most frequent aspects of EBVaGC, including the specific features of this GC subtype, data regarding the potential steps of EBVaGC carcinogenesis, and perspectives on treatment opportunities.
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de Fátima Aquino Moreira-Nunes C, de Souza Almeida Titan Martins CN, Feio D, Lima IK, Lamarão LM, de Souza CRT, Costa IB, da Silva Maués JH, Soares PC, de Assumpção PP, Burbano RMR. PD-L1 Expression Associated with Epstein-Barr Virus Status and Patients' Survival in a Large Cohort of Gastric Cancer Patients in Northern Brazil. Cancers (Basel) 2021; 13:3107. [PMID: 34206307 PMCID: PMC8268941 DOI: 10.3390/cancers13133107] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 05/31/2021] [Accepted: 06/03/2021] [Indexed: 12/15/2022] Open
Abstract
Gastric cancer (GC) is a worldwide health problem, making it one of the most common types of cancer, in fifth place of all tumor types, and the third highest cause of cancer deaths in the world. There is a subgroup of GC that consists of tumors infected with the Epstein-Barr virus (EBV) and is characterized mainly by the overexpression of programmed cell death protein-ligand-1 (PD-L1). In the present study, we present histopathological and survival data of a thousand GC patients, associated with EBV status and PD-L1 expression. Of the thousand tumors analyzed, 190 were EBV-positive and the vast majority (86.8%) had a high relative expression of mRNA and PD-L1 protein (p < 0.0001) in relation to non-neoplastic control. On the other hand, in EBV-negative samples, the majority had a low PD-L1 expression of RNA and protein (p < 0.0001). In the Kaplan-Meier analysis, the probability of survival and increased overall survival of EBV-positive GC patients was impacted by the PD-L1 overexpression (p < 0.0001 and p = 0.004, respectively). However, the PD-L1 low expression was correlated with low overall survival in those patients. Patients with GC positive for EBV, presenting PD-L1 overexpression can benefit from immunotherapy treatments and performing the quantification of PD-L1 in gastric neoplasms should be adopted as routine.
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Affiliation(s)
- Caroline de Fátima Aquino Moreira-Nunes
- Laboratory of Molecular Biology, Department of Clinical Medicine, Ophir Loyola Hospital, Belém, 66063-240 PA, Brazil; (C.N.d.S.A.T.M.); (D.F.); (I.K.L.); (P.C.S.)
- Laboratory of Pharmacogenetics, Department of Medicine, Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza, 60430-275 CE, Brazil
| | | | - Danielle Feio
- Laboratory of Molecular Biology, Department of Clinical Medicine, Ophir Loyola Hospital, Belém, 66063-240 PA, Brazil; (C.N.d.S.A.T.M.); (D.F.); (I.K.L.); (P.C.S.)
| | - Isamu Komatsu Lima
- Laboratory of Molecular Biology, Department of Clinical Medicine, Ophir Loyola Hospital, Belém, 66063-240 PA, Brazil; (C.N.d.S.A.T.M.); (D.F.); (I.K.L.); (P.C.S.)
| | - Leticia Martins Lamarão
- Foundation Center for Hemotherapy and Hematology of Pará (HEMOPA), Department of Sorology, Belém, 66033-000 PA, Brazil;
| | | | - Igor Brasil Costa
- Department of Virology, Evandro Chagas Institute, Ananindeua, 67030-000 PA, Brazil;
| | - Jersey Heitor da Silva Maués
- Hematology and Transfusion Medicine Center, Laboratory of Molecular and Cell Biology, Department of Medicine, University of Campinas, Campinas, 13083-970 SP, Brazil;
| | - Paulo Cardoso Soares
- Laboratory of Molecular Biology, Department of Clinical Medicine, Ophir Loyola Hospital, Belém, 66063-240 PA, Brazil; (C.N.d.S.A.T.M.); (D.F.); (I.K.L.); (P.C.S.)
| | - Paulo Pimentel de Assumpção
- Oncology Research Center, Department of Biological Sciences, Federal University of Pará, Belém, 66073-005 PA, Brazil;
| | - Rommel Mário Rodríguez Burbano
- Laboratory of Molecular Biology, Department of Clinical Medicine, Ophir Loyola Hospital, Belém, 66063-240 PA, Brazil; (C.N.d.S.A.T.M.); (D.F.); (I.K.L.); (P.C.S.)
- Oncology Research Center, Department of Biological Sciences, Federal University of Pará, Belém, 66073-005 PA, Brazil;
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11
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TCGA-TCIA-Based CT Radiomics Study for Noninvasively Predicting Epstein-Barr Virus Status in Gastric Cancer. AJR Am J Roentgenol 2021; 217:124-134. [PMID: 33955777 DOI: 10.2214/ajr.20.23534] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE. The purpose of this study was to investigate the value of TCGA-TCIA (The Cancer Genome Atlas and The Cancer Imaging Archive)-based CT radiomics for noninvasive prediction of Epstein-Barr virus (EBV) status in gastric cancer (GC). MATERIALS AND METHODS. A total of 133 patients with pathologically confirmed GC (94 in the training cohort and 39 in the validation cohort) who were identified from the TCGA-TCIA public data repository and two hospitals were retrospectively enrolled in the study. Two-dimensional and 3D radiomics features were extracted to construct corresponding radiomics signatures. Then, 2D and 3D nomograms were built by combining radiomics signatures and clinical information on the basis of multivariable analysis. Their performance and clinical practicability were determined, validated, and compared with respect to discrimination, calibration, reclassification, and time spent on tumor segmentation. RESULTS. Both 2D and 3D nomograms were robust and showed good calibration. The AUCs of the 2D and 3D nomograms showed no significant difference in the training cohort (0.919 vs 0.945, respectively; p = .41) or validation cohort (0.939 vs 0.955, respectively; p = .71). The net reclassification index showed that the 3D nomogram revealed no significant improvement in risk reclassification when compared with the 2D nomogram in the training cohort (net reclassification index, 0.68%; p = .14) and the validation cohort (net reclassification index, 6.06%; p = .08). Of note, the time spent on 3D segmentation (median, 907 seconds) was higher than that spent on 2D segmentation (median, 129 seconds). CONCLUSION. The 2D and 3D radiomics nomograms might have the potential to be used as effective tools for prediction of EBV in GC. When time spent on segmentation is considered, the 2D nomogram is more highly recommended for clinical application.
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12
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Liu W, Zhang Y, Luo B. Long Non-coding RNAs in Gammaherpesvirus Infections: Their Roles in Tumorigenic Mechanisms. Front Microbiol 2021; 11:604536. [PMID: 33519750 PMCID: PMC7843584 DOI: 10.3389/fmicb.2020.604536] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 12/10/2020] [Indexed: 12/12/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) regulate gene expression at the epigenetic, transcriptional, or posttranscriptional level by interacting with protein, DNA, and RNA. Emerging evidence suggests that various lncRNAs are abnormally expressed and play indispensable roles in virus-triggered cancers. Besides, a growing number of studies have shown that virus-encoded lncRNAs participate in tumorigenesis. However, the functions of most lncRNAs in tumors caused by oncogenic viruses and their underlying mechanisms remain largely unknown. In this review, we summarize current findings regarding lncRNAs involved in cancers caused by Epstein–Barr virus (EBV) and Kaposi’s sarcoma herpesvirus (KSHV). Additionally, we discuss the contribution of lncRNAs to tumor occurrence, development, invasion, and metastasis; the roles of lncRNAs in key signaling pathways and their potential as biomarkers and therapeutic targets for tumor diagnostics and treatment.
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Affiliation(s)
- Wen Liu
- Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao, China
| | - Yan Zhang
- Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao, China.,Department of Clinical Laboratory, Zibo Central Hospital, Zibo, China
| | - Bing Luo
- Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao, China
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Pyo JS, Kim NY, Kang DW. Clinicopathological Significance of EBV-Infected Gastric Carcinomas: A Meta-Analysis. ACTA ACUST UNITED AC 2020; 56:medicina56070345. [PMID: 32668573 PMCID: PMC7404405 DOI: 10.3390/medicina56070345] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 07/02/2020] [Accepted: 07/09/2020] [Indexed: 02/06/2023]
Abstract
Background and objectives: The present study aims to elucidate the clinicopathologic significance of Epstein-Barr virus (EBV) infection in gastric carcinomas (GCs) through a meta-analysis. Materials and Methods: Sixty-one eligible studies were included in the present meta-analysis. The included patients, with and without EBV infection, were 2063 and 17,684, respectively. We investigated the clinicopathologic characteristics and various biomarkers, including programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs). Results: The estimated EBV-infected rate of GCs was 0.113 (95% confidence interval (CI): 0.088-0.143). The EBV infection rates in GC cells were 0.138 (95% CI: 0.096-0.194), 0.103 (95% CI: 0.077-0.137), 0.080 (95% CI: 0.061-0.106), and 0.042 (95% CI: 0.016-0.106) in the population of Asia, America, Europe, and Africa, respectively. There was a significant difference between EBV-infected and noninfected GCs in the male: female ratio, but not other clinicopathological characteristics. EBV infection rates were higher in GC with lymphoid stroma (0.573, 95% CI: 0.428-0.706) than other histologic types of GCs. There were significant differences in high AT-rich interactive domain-containing protein 1A (ARID1A) and PD-L1 expressions, and high CD8+ TILs between EBV-infected and noninfected GCs. Conclusions: Our results showed that EBV infection of GCs was frequently found in male patients and GCs with lymphoid stroma. EBV infection was significantly correlated with ARID1A and PD-L1 expressions and CD8+ TILs in GCs.
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Affiliation(s)
- Jung-Soo Pyo
- Department of Pathology, Daejeon Eulji University Hospital, Eulji University School of Medicine, Daejeon 35233, Korea;
| | - Nae-Yu Kim
- Department of Internal Medicine, Daejeon Eulji University Hospital, Eulji University School of Medicine, Daejeon 35233, Korea;
| | - Dong-Wook Kang
- Department of Pathology, Chungnam National University Sejong Hospital, 20 Bodeum 7-ro, Sejong 30099, Korea
- Department of Pathology, Chungnam National University School of Medicine, 266 Munhwa Street, Daejeon 35015, Korea
- Correspondence: ; Tel.: +82-10-8561-9895
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14
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Tavakoli A, Monavari SH, Solaymani Mohammadi F, Kiani SJ, Armat S, Farahmand M. Association between Epstein-Barr virus infection and gastric cancer: a systematic review and meta-analysis. BMC Cancer 2020; 20:493. [PMID: 32487043 PMCID: PMC7268387 DOI: 10.1186/s12885-020-07013-x] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 05/27/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Numerous studies conducted over the past 30 years have pointed to the presence of Epstein-Barr virus (EBV) in gastric cancer samples. This study was aimed to provide a meta-analytic review of the prevalence of EBV in gastric cancer patients, and to clarify the relationship between EBV infection and gastric cancer. METHODS A literature search was performed electronically using online databases for English language publications until July 1, 2019. The pooled EBV prevalence and 95% confidence intervals (CIs) were estimated using a random-effects model. To determine the association between EBV and gastric cancer, pooled odds ratio (OR) and its 95% CI were computed for case-control studies. Two separate analyses were performed on data from case-control studies with matched and non-match pairs designs to calculate the pooled estimates of ORs. RESULTS The pooled prevalence of EBV in 20,361 gastric cancer patients was 8.77% (95% CI: 7.73-9.92%; I2 = 83.2%). There were 20 studies with matched pairs design, including tumor and tumor-adjacent normal tissue pairs from 4116 gastric cancer patients. The pooled ORs were 18.56 (95% CI: 15.68-21.97; I2 = 55.4%) for studies with matched pairs design and 3.31 (95% CI: 0.95-11.54; I2 = 55.0%) for studies with non-matched pairs design. The proportion of EBV-associated gastric cancer among male cases was significantly higher than among female cases (10.83%, vs. 5.72%) (P < 0.0001). However, the pooled OR estimate for EBV-associated gastric cancer was significantly higher among females (21.47; 95% CI: 15.55-29.63; I2 = 0%) than in males (14.07; 95% CI: 10.46-18.93; I2 = 49.0%) (P = 0.06). EBV was more prevalent in the cardia (12.47%) and the body (11.68%) compared to the antrum (6.29%) (P = 0.0002). CONCLUSIONS EBV infection is associated with more than 18 times increase the risk of gastric cancer. Although the prevalence of EBV was higher in male patients than in female patients with gastric cancer, women are more likely than men to develop EBV-associated gastric cancer. Our findings showed that using tumor-adjacent normal tissues as the control group provides more robust and accurate results regarding the relationship between EBV infection and gastric cancer.
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Affiliation(s)
- Ahmad Tavakoli
- Research Center of Pediatric Infectious Diseases, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
| | - Seyed Hamidreza Monavari
- Department of Medical Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | | | - Seyed Jalal Kiani
- Department of Medical Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Saber Armat
- Department of Biology, College of Science, Shiraz University, Shiraz, Iran
| | - Mohammad Farahmand
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
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15
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Liu W, Luo B. The impact of EBV on the epigenetics of gastric carcinoma. Future Virol 2020. [DOI: 10.2217/fvl-2019-0148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
EBV is an important human tumor virus and is closely related to the occurrence of a variety of tumors, involving 10% of gastric cancer. In EBV-associated gastric carcinoma (EBVaGC), EBV expresses restrict viral genes including EBV nuclear antigen 1, EBV encoded small RNAs, Bam HI-A rightward transcripts, latent membrane protein 2A and miRNAs. The role of EBV in gastric carcinogenesis has received increasing attention and is considered to be another pathogenic factor in addition to Helicobacter pylori. A typical characteristic of EBVaGC is the extensive methylation of viral and host genome. Combined with other epigenetic mechanisms, EBV infection acts as an epigenetic driver of EBVaGC oncogenesis. In this review we discuss recent findings of EBV effect on host epigenetic alterations in EBVaGC and its role in oncogenic process.
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Affiliation(s)
- Wen Liu
- Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao, PR China
| | - Bing Luo
- Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao, PR China
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16
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Corvalán AH, Ruedlinger J, de Mayo T, Polakovicova I, Gonzalez-Hormazabal P, Aguayo F. The Phylogeographic Diversity of EBV and Admixed Ancestry in the Americas⁻Another Model of Disrupted Human-Pathogen Co-Evolution. Cancers (Basel) 2019; 11:cancers11020217. [PMID: 30769835 PMCID: PMC6406347 DOI: 10.3390/cancers11020217] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Revised: 12/19/2018] [Accepted: 12/20/2018] [Indexed: 12/24/2022] Open
Abstract
Epstein-Barr virus (EBV) is an etiological agent for gastric cancer with significant worldwide variations. Molecular characterizations of EBV have shown phylogeographical variations among healthy populations and in EBV-associated diseases, particularly the cosegregated BamHI-I fragment and XhoI restriction site of exon 1 of the LMP-1 gene. In the Americas, both cosegregated variants are present in EBV carriers, which aligns with the history of Asian and European human migration to this continent. Furthermore, novel recombinant variants have been found, reflecting the genetic makeup of this continent. However, in the case of EBV-associated gastric cancer (EBV-associated GC), the cosegregated European BamHI-“i” fragment and XhoI restriction site strain prevails. Thus, we propose that a disrupted coevolution between viral phylogeographical strains and mixed human ancestry in the Americas might explain the high prevalence of this particular gastric cancer subtype. This cosegregated region contains two relevant transcripts for EBV-associated GC, the BARF-1 and miR-BARTs. Thus, genome-wide association studies (GWAS) or targeted sequencing of both transcripts may be required to clarify their role as a potential source of this disrupted coevolution.
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Affiliation(s)
- Alejandro H Corvalán
- Department of Hematology and Oncology, Pontificia Universidad Catolica de Chile, Santiago 8330034, Chile.
- Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Catolica de Chile, Santiago 8330034, Chile.
| | - Jenny Ruedlinger
- Department of Hematology and Oncology, Pontificia Universidad Catolica de Chile, Santiago 8330034, Chile.
- Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Catolica de Chile, Santiago 8330034, Chile.
| | - Tomas de Mayo
- Department of Hematology and Oncology, Pontificia Universidad Catolica de Chile, Santiago 8330034, Chile.
- Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Catolica de Chile, Santiago 8330034, Chile.
- Faculty of Sciences, School of Medicine, Universidad Mayor, Santiago 7510041, Chile.
| | - Iva Polakovicova
- Department of Hematology and Oncology, Pontificia Universidad Catolica de Chile, Santiago 8330034, Chile.
- Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Catolica de Chile, Santiago 8330034, Chile.
| | - Patricio Gonzalez-Hormazabal
- Program of Human Genetics, Instituto Ciencias Biomedicas, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile.
| | - Francisco Aguayo
- Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Catolica de Chile, Santiago 8330034, Chile.
- Department of Basic and Clinical Oncology, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile.
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Amoueian S, Attaranzadeh A, Gholamimoallem Z, Sadeghi M, Hashemi SM, Allahyari A. Epstein–Barr Virus Infection in Adult Patients with Gastric Cancer in Northeast of Iran. Indian J Med Paediatr Oncol 2018. [DOI: 10.4103/ijmpo.ijmpo_132_17] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Abstract
Background: Epstein–Barr virus (EBV) is a DNA virus from human herpes virus that associates with many of the human cancers including gastric cancer (GC). Aims: The aim of the present study was to report infection of EBV in adult patients with GC in Northeast of Iran and the correlation between a number of clinicopathology factors with EBV status. Materials and Methods: In a case–control study in 2016, 56 GC patients and 56 controls were selected for the analysis. All patients had gastric adenocarcinoma untreated patients with age >18 years. EBV status detected by the polymerase chain reaction method. Results: Out of 56 GC patients, 35 (62.5%) were EBV positivity and out of 56 controls 3 (5.4%) were EBV positivity (P < 0.001). There is not a significant correlation between the variables with the EBV status (P > 0.05). Furthermore, the progression-free survival rate for the patients with EBV negativity was 95.2% compared with 82.9% for EBV positivity (P = 0.174). Conclusions: This study reported a very high prevalence of EBV-associated GC in the Northeast of Iran compared with other areas of the World and showed a significant correlation between EBV infection and incidence of GC.
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Affiliation(s)
- Sakineh Amoueian
- Department of Pathology, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Armin Attaranzadeh
- Department of Pathology, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zeinab Gholamimoallem
- Department of Hematology and Medical Oncology, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Masoud Sadeghi
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Seyed-Mehdi Hashemi
- Department of Hematology and Medical Oncology, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Abolghasem Allahyari
- Department of Hematology and Medical Oncology, Mashhad University of Medical Sciences, Mashhad, Iran
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18
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Naseem M, Barzi A, Brezden-Masley C, Puccini A, Berger MD, Tokunaga R, Battaglin F, Soni S, McSkane M, Zhang W, Lenz HJ. Outlooks on Epstein-Barr virus associated gastric cancer. Cancer Treat Rev 2018; 66:15-22. [PMID: 29631196 DOI: 10.1016/j.ctrv.2018.03.006] [Citation(s) in RCA: 143] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Revised: 03/28/2018] [Accepted: 03/29/2018] [Indexed: 12/11/2022]
Abstract
Epstein-Barr virus associated gastric cancer (EBVaGC) comprises approximately 10% of gastric carcinomas. Multiple factors contribute to tumorigenesis, including EBV driven hypermethylation of tumor suppressor genes, inflammatory changes in gastric mucosa, host immune evasion by EBV and changes in cell cycle pathways. The unique molecular characteristics of EBVaGC, such as programmed death ligand 1 (PD-L1) overexpression, highlight the potential for using EBV as a biomarker for response to immunotherapy. Few studies have reported benefit from immunotherapy in EBV positive cancers, and clinical trials investigating the impact of checkpoint inhibitors in EBVaGC are currently underway. This review provides the most recent updates on molecular pathophysiology, epidemiology, clinical features and treatment advances pertaining to EBVaGC.
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Affiliation(s)
- Madiha Naseem
- Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, USA
| | - Afsaneh Barzi
- Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, USA
| | - Christine Brezden-Masley
- Division of Hematology/Oncology, Department of Medicine, St. Michael's Hospital, University of Toronto, Canada
| | - Alberto Puccini
- Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, USA
| | - Martin D Berger
- Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, USA
| | - Ryuma Tokunaga
- Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, USA
| | - Francesca Battaglin
- Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, USA; Clinical and Experimental Oncology Department, Medical Oncology Unit 1, Veneto Institute of Oncology IRCCS, Padua, Italy
| | - Shivani Soni
- Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, USA
| | - Michelle McSkane
- Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, USA
| | - Wu Zhang
- Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, USA
| | - Heinz-Josef Lenz
- Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, USA.
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Ribeiro J, Oliveira A, Malta M, Oliveira C, Silva F, Galaghar A, Afonso LP, Neves MC, Medeiros R, Pimentel-Nunes P, Sousa H. Clinical and pathological characterization of Epstein-Barr virus-associated gastric carcinomas in Portugal. World J Gastroenterol 2017; 23:7292-7302. [PMID: 29142476 PMCID: PMC5677199 DOI: 10.3748/wjg.v23.i40.7292] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Revised: 07/27/2017] [Accepted: 08/15/2017] [Indexed: 02/07/2023] Open
Abstract
AIM To determine the prevalence of Epstein-Barr virus (EBV)-associated gastric carcinomas in the North Region of Portugal and to study its clinicopathological characteristics.
METHODS We have performed a retrospective study including a total of 179 consecutive patients with gastric cancer (GC) submitted to gastrectomy during 2011 at the Portuguese Oncology Institute of Porto. Clinical and pathological data was collected from individual clinical records and inserted on a database with unique codification. Tumour tissues were collected from the institutional tumour bank. EBV was detected by in situ hybridization for the detection of EBV-encoded small RNAs (EBERs) and EBV latent proteins (LMP1 and LMP2A) were detected by immunohistochemistry.
RESULTS The analysis showed that EBV-associated gastric carcinomas (EBVaGC) represents 8.4% (15/179) of all GC cases, with a significant differential distribution among histological types (P < 0.001): 100% (3/3) of medullary carcinomas, 100% (1/1) of adenosquamous carcinoma, 8.7% (8/92) of tubular adenocarcinomas, 8.0% (2/25) of mixed carcinomas and 2% (1/51) in poorly cohesive carcinomas. The analysis revealed a higher predominance of EBVaGC in the upper third and middle (cardia, fundus and body) of the stomach (P = 0.041), a significant lower number of regional lymph nodes invasion (P = 0.025) and a tendency for better prognosis (P = 0.222). EBV latent protein expression revealed that all EBVaGC cases were LMP1-negative, nevertheless 6 cases (40%) expressed LPM2A, which reveals that these cases show a distinct EBV-Latency profile (latency II-like).
CONCLUSION EBVaGC represents 8.4% of all GC in the North Region of Portugal. The EBV-infected patients have specific clinic-pathological features that should be further explored to develop new strategies of management and treatment.
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Affiliation(s)
- Joana Ribeiro
- Molecular Oncology and Viral Pathology Group, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
- Faculty of Medicine of Porto University, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
| | - Andreia Oliveira
- Molecular Oncology and Viral Pathology Group, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
| | - Mariana Malta
- Molecular Oncology and Viral Pathology Group, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
| | - Claudia Oliveira
- Molecular Oncology and Viral Pathology Group, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
| | - Fernanda Silva
- Department of Pathology, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
| | - Ana Galaghar
- Department of Pathology, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
| | - Luís Pedro Afonso
- Department of Pathology, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
| | - Maria Cassiano Neves
- Medical Oncology Department, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
- Instituto CUF de Oncologia, Rua Mário Botas, 1998-018 Lisbon, Portugal
| | - Rui Medeiros
- Molecular Oncology and Viral Pathology Group, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
- Virology Service, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
- Research Department - Portuguese League Against Cancer (Liga Portuguesa Contra o Cancro - Núcleo Regional do Norte), Estrada Interior da Circunvalação nº 6657, 4200- 172 Porto, Portugal
| | - Pedro Pimentel-Nunes
- Gastroenterology Service, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
- CINTESIS - Center for Health Technology and Services Research (Centro de Investigação Médica, Faculdade de Medicina da Universidade do Porto), Rua Dr. Plácido da Costa, 4200-450 Porto, Portugal
| | - Hugo Sousa
- Molecular Oncology and Viral Pathology Group, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
- Virology Service, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
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20
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Popa E, Schnoll‐Sussman F, Jesudian A, Nandakumar G, Shah MA. Uncommon Cancers of the Stomach. TEXTBOOK OF UNCOMMON CANCER 2017:395-415. [DOI: 10.1002/9781119196235.ch27] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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21
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朱 晓, 李 夏, 李 素, 于 红. Advances in research of Epstein-Barr virus-associated gastric carcinoma. Shijie Huaren Xiaohua Zazhi 2017; 25:1375. [DOI: 10.11569/wcjd.v25.i15.1375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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22
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A protein and mRNA expression-based classification of gastric cancer. Mod Pathol 2016; 29:772-84. [PMID: 27032689 DOI: 10.1038/modpathol.2016.55] [Citation(s) in RCA: 121] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2015] [Revised: 02/09/2016] [Accepted: 02/10/2016] [Indexed: 12/14/2022]
Abstract
The overall survival of gastric carcinoma patients remains poor despite improved control over known risk factors and surveillance. This highlights the need for new classifications, driven towards identification of potential therapeutic targets. Using sophisticated molecular technologies and analysis, three groups recently provided genetic and epigenetic molecular classifications of gastric cancer (The Cancer Genome Atlas, 'Singapore-Duke' study, and Asian Cancer Research Group). Suggested by these classifications, here, we examined the expression of 14 biomarkers in a cohort of 146 gastric adenocarcinomas and performed unsupervised hierarchical clustering analysis using less expensive and widely available immunohistochemistry and in situ hybridization. Ultimately, we identified five groups of gastric cancers based on Epstein-Barr virus (EBV) positivity, microsatellite instability, aberrant E-cadherin, and p53 expression; the remaining cases constituted a group characterized by normal p53 expression. In addition, the five categories correspond to the reported molecular subgroups by virtue of clinicopathologic features. Furthermore, evaluation between these clusters and survival using the Cox proportional hazards model showed a trend for superior survival in the EBV and microsatellite-instable related adenocarcinomas. In conclusion, we offer as a proposal a simplified algorithm that is able to reproduce the recently proposed molecular subgroups of gastric adenocarcinoma, using immunohistochemical and in situ hybridization techniques.
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Bae JM, Kim EH. Epstein-Barr Virus and Gastric Cancer Risk: A Meta-analysis With Meta-regression of Case-control Studies. J Prev Med Public Health 2016; 49:97-107. [PMID: 27055546 PMCID: PMC4829373 DOI: 10.3961/jpmph.15.068] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2015] [Accepted: 02/01/2016] [Indexed: 12/13/2022] Open
Abstract
Objectives: Research on how the risk of gastric cancer increases with Epstein-Barr virus (EBV) infection is lacking. In a systematic review that investigated studies published until September 2014, the authors did not calculate the summary odds ratio (SOR) due to heterogeneity across studies. Therefore, we include here additional studies published until October 2015 and conduct a meta-analysis with meta-regression that controls for the heterogeneity among studies. Methods: Using the studies selected in the previously published systematic review, we formulated lists of references, cited articles, and related articles provided by PubMed. From the lists, only case-control studies that detected EBV in tissue samples were selected. In order to control for the heterogeneity among studies, subgroup analysis and meta-regression were performed. Results: In the 33 case-control results with adjacent non-cancer tissue, the total number of test samples in the case and control groups was 5280 and 4962, respectively. In the 14 case-control results with normal tissue, the total number of test samples in case and control groups was 1393 and 945, respectively. Upon meta-regression, the type of control tissue was found to be a statistically significant variable with regard to heterogeneity. When the control tissue was normal tissue of healthy individuals, the SOR was 3.41 (95% CI, 1.78 to 6.51; I-squared, 65.5%). Conclusions: The results of the present study support the argument that EBV infection increases the risk of gastric cancer. In the future, age-matched and sex-matched case-control studies should be conducted.
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Affiliation(s)
- Jong-Myon Bae
- Department of Preventive Medicine, Jeju National University School of Medicine, Jeju, Korea
| | - Eun Hee Kim
- Department of Preventive Medicine, Jeju National University School of Medicine, Jeju, Korea
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24
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Liu X, Liu J, Qiu H, Kong P, Chen S, Li W, Zhan Y, Li Y, Chen Y, Zhou Z, Xu D, Sun X. Prognostic significance of Epstein-Barr virus infection in gastric cancer: a meta-analysis. BMC Cancer 2015; 15:782. [PMID: 26498209 PMCID: PMC4619309 DOI: 10.1186/s12885-015-1813-9] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2015] [Accepted: 10/16/2015] [Indexed: 02/08/2023] Open
Abstract
Background The prognostic significance of Epstein-Barr virus (EBV) infection in gastric cancer (GC) remains unclear. Recently, a number of studies have investigated the association between EBV infection and the prognosis of GC with controversial results. We therefore conducted a meta-analysis to assess its prognostic significance. Methods PubMed and EMBASE were searched for studies up to October 1, 2014. We investigated the association between EBV infection with survival in patients with GC. The pooled hazard ratio (HR) and its 95 % confidence interval (CI) were calculated to evaluate risk. Results A final analysis of 8,336 patients with GC from 24 studies was performed. Our analysis results indicated that the pooled HR was 0.67 (95 % CI: 0.55–0.79; Z = 11.18, P < 0.001). Subgroup analyses stratified by region revealed that the protective role of EBV infection only remained in the Asian population (HR: 0.62, 95 % CI: 0.48–0.75; P < 0.001). When stratified by study quality and statistical methodology, the protective role could also be identified in high quality studies (HR: 0.67, 95 % CI: 0.55–0.79) and in univariate analysis studies (HR: 0.62, 95 % CI: 0.50–0.74). There was no evidence of significant heterogeneity and publication bias. Conclusions The presence of EBV has a favorable impact on GC patient’s survival, especially in an Asian population. Future updated studies, especially large-scale randomized controlled studies stratified by region, are warranted as validation studies. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1813-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Xuechao Liu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. .,Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, 651# East Dongfeng Road, Guangzhou, 510000, Guangdong Province, China.
| | - Jianjun Liu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. .,Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, 651# East Dongfeng Road, Guangzhou, 510000, Guangdong Province, China.
| | - Haibo Qiu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. .,Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, 651# East Dongfeng Road, Guangzhou, 510000, Guangdong Province, China.
| | - Pengfei Kong
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. .,Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, 651# East Dongfeng Road, Guangzhou, 510000, Guangdong Province, China.
| | - Shangxiang Chen
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. .,Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, 651# East Dongfeng Road, Guangzhou, 510000, Guangdong Province, China.
| | - Wei Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. .,Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, 651# East Dongfeng Road, Guangzhou, 510000, Guangdong Province, China.
| | - Youqing Zhan
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. .,Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, 651# East Dongfeng Road, Guangzhou, 510000, Guangdong Province, China.
| | - Yuanfang Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. .,Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, 651# East Dongfeng Road, Guangzhou, 510000, Guangdong Province, China.
| | - Yingbo Chen
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. .,Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, 651# East Dongfeng Road, Guangzhou, 510000, Guangdong Province, China.
| | - Zhiwei Zhou
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. .,Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, 651# East Dongfeng Road, Guangzhou, 510000, Guangdong Province, China.
| | - Dazhi Xu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. .,Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, 651# East Dongfeng Road, Guangzhou, 510000, Guangdong Province, China.
| | - Xiaowei Sun
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. .,Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, 651# East Dongfeng Road, Guangzhou, 510000, Guangdong Province, China.
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Cárdenas-Mondragón MG, Torres J, Flores-Luna L, Camorlinga-Ponce M, Carreón-Talavera R, Gomez-Delgado A, Kasamatsu E, Fuentes-Pananá EM. Case–control study of Epstein–Barr virus and Helicobacter pylori serology in Latin American patients with gastric disease. Br J Cancer 2015; 112:1866-73. [PMID: 25996206 PMCID: PMC4580389 DOI: 10.1038/bjc.2015.175] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Revised: 04/21/2015] [Accepted: 04/29/2015] [Indexed: 02/07/2023] Open
Abstract
Background: Chronic tissue damage induced by Helicobacter pylori (HP)-driven inflammation is considered the main risk of gastric carcinoma (GC). Epstein–Barr virus (EBV) infection has also been associated with GC. In this study, we aim to address the role of EBV in inflammatory GC precursor lesions and its added risk to HP infection. Methods: Antibodies against EBV, HP and the bacterial virulence factor CagA were measured in sera from 525 Mexican and Paraguayan patients with gastric disease. Gastric samples were characterised according to the updated Sydney classification and associations were estimated between antibody responses and severity of both tissue damage and inflammation. Results: We found significant associations (odd ratios and trends) between EBV and HP copositivity and premalignant lesions and intestinal-type GC. The EBV and HP coinfection was also significantly associated with increased infiltration of immune cells. No association was found between EBV and the less inflammation-driven diffuse-type GC. Conclusions: Our study suggests that EBV co-participates with HP to induce severe inflammation, increasing the risk of progression to intestinal-type GC.
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Affiliation(s)
- M G Cárdenas-Mondragón
- Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias (UIMEIP), Hospital de Pediatría, CMN Siglo-XXI, Instituto Mexicano del Seguro Social (IMSS), Avenida Cuauhtémoc 330, Colonia Doctores, Delegación Cuauhtémoc, Ciudad de México, DF, CP 06720, México
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Chen XZ, Chen H, Castro FA, Hu JK, Brenner H. Epstein-Barr virus infection and gastric cancer: a systematic review. Medicine (Baltimore) 2015; 94:e792. [PMID: 25997049 PMCID: PMC4602887 DOI: 10.1097/md.0000000000000792] [Citation(s) in RCA: 94] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2015] [Revised: 03/26/2015] [Accepted: 03/28/2015] [Indexed: 02/07/2023] Open
Abstract
Epstein-Barr virus (EBV) infection is found in a subset of gastric cancers. Previous reviews have exclusively focused on EBV-encoded small RNA (EBER) positivity in gastric cancer tissues, but a comprehensive evaluation of other type of studies is lacking.We searched the PubMed database up to September, 2014, and performed a systematic review.We considered studies comparing EBV nucleic acids positivity in gastric cancer tissue with positivity in either adjacent non-tumor tissue of cancer patients or non-tumor mucosa from healthy individuals, patients with benign gastric diseases, or deceased individuals. We also considered studies comparing EBV antibodies in serum from cancer patients and healthy controls.Selection of potentially eligible studies and data extraction were performed by 2 independent reviewers. Due to the heterogeneity of studies, we did not perform formal meta-analysis.Forty-seven studies (8069 cases and 1840 controls) were identified. EBER positivity determined by in situ hybridization (ISH) was significantly higher in cancer tissues (range 5.0%-17.9%) than in adjacent mucosa from the same patients or biopsies from all control groups (almost 0%). High EBV nuclear antigen-1 (EBNA-1) positivity by PCR was found in gastric cancer tissues, but most were not validated by ISH or adjusted for inflammatory severity and lymphocyte infiltration. Only 4 studies tested for EBV antibodies, with large variation in the seropositivities of different antibodies in both cases and controls, and did not find an association between EBV seropositivity and gastric cancer.In summary, tissue-based ISH methods strongly suggest an association between EBV infection and gastric cancer, but PCR method alone is invalid to confirm such association. Very limited evidence from serological studies and the lack of novel antibodies warrant further investigations to identify potential risk factors of EBV for gastric cancer.
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Affiliation(s)
- Xin-Zu Chen
- From the Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany (X-ZC, HC, FAC, HB); Department of Gastrointestinal Surgery (X-ZC, J-KH); Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China (X-ZC, J-KH); and German Cancer Consortium (DKTK), Heidelberg, Germany (HB)
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27
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Khan G, Hashim MJ. Global burden of deaths from Epstein-Barr virus attributable malignancies 1990-2010. Infect Agent Cancer 2014; 9:38. [PMID: 25473414 PMCID: PMC4253616 DOI: 10.1186/1750-9378-9-38] [Citation(s) in RCA: 177] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Accepted: 10/09/2014] [Indexed: 12/26/2022] Open
Abstract
Background Epstein-Barr virus (EBV) is an oncogenic virus implicated in the pathogenesis of a number of human malignancies of both lymphoid and epithelial origin. Thus, a comprehensive and up-to-date analysis focused on the global burden of EBV-attributable malignancies is of significant interest. Methods Based on published studies, we estimated the proportion of Burkitt’s lymphoma (BL), Hodgkin’s lymphoma (HL), nasopharyngeal carcinoma NPC), gastric carcinoma (GC) and post-transplant lymphoproliferative disease (PTLD) attributable to EBV, taking into consideration age, sex and geographical variations. This proportion was then imputed into the Global Burden of Disease 2010 dataset to determine the global burden of each EBV-attributable malignancy in males and females in 20 different age groups and 21 world regions from 1990 to 2010. Results The analysis showed that the combined global burden of deaths in 2010 from all EBV-attributable malignancies was 142,979, representing 1.8% of all cancer deaths. This burden has increased by 14.6% over a period of 20 years. All 5 EBV-attributable malignancies were more common in males in all geographical regions (ratio of 2.6:1). Gastric cancer and NPC accounted for 92% of all EBV-attributable cancer deaths. Almost 50% of EBV-attributed malignancies occurred in East Asia. This region also had the highest age-standardized death rates for both NPC and GC. Conclusions Approximately 143,000 deaths in 2010 were attributed to EBV-associated malignancies. This figure is likely to be an underestimate since some of the less prevalent EBV-associated malignancies have not been included. Moreover, the global increase in population and life-expectancy will further increase the overall burden of EBV-associated cancer deaths. Development of a suitable vaccine could have a substantial impact on reducing this burden. Electronic supplementary material The online version of this article (doi:10.1186/1750-9378-9-38) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Gulfaraz Khan
- Department of Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Muhammad Jawad Hashim
- Department of Family Medicine, College of Medicine and Health Sciences (Tawam Hospital Campus), United Arab Emirates University, Al Ain, P.O. Box 17666, United Arab Emirates
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28
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Zeng Z, Huang H, Huang L, Sun M, Yan Q, Song Y, Wei F, Bo H, Gong Z, Zeng Y, Li Q, Zhang W, Li X, Xiang B, Li X, Li Y, Xiong W, Li G. Regulation network and expression profiles of Epstein-Barr virus-encoded microRNAs and their potential target host genes in nasopharyngeal carcinomas. SCIENCE CHINA-LIFE SCIENCES 2014; 57:315-326. [PMID: 24532457 DOI: 10.1007/s11427-013-4577-y] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2013] [Accepted: 10/25/2013] [Indexed: 12/11/2022]
Abstract
Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC) tumorigenesis. However, the mechanism(s) connecting EBV infection and NPC remain unclear. Recently, a new class of EBV microRNAs (miRNAs) has been described. To determine how EBV miRNAs control the expression of host genes, and to understand their potential role in NPC tumorigenesis, we profiled the expression of 44 mature EBV miRNAs and potential host genes in NPC and non-tumor nasopharyngeal epithelial tissues. We found that 40 EBV miRNAs from the BART transcript were highly expressed in NPC. Analysis of potential BART miRNA target genes revealed that 3140 genes and several important pathways might be involved in the carcinogenesis of NPC. A total of 105 genes with potential EBV miRNA binding sites were significantly downregulated, suggesting that EBV miRNAs may regulate these genes and contribute to NPC carcinogenesis. An EBV miRNA and host gene regulation network was generated to provide useful clues for validating of EBV miRNA functions in NPC tumorigenesis.
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Affiliation(s)
- ZhaoYang Zeng
- Hunan Provincial Tumor Hospital, Xiangya School of Medicine, Central South University, Changsha, 410013, China.,Key Laboratory of Carcinogenesis of Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, 410078, China.,Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, 410013, China
| | - HongBin Huang
- Key Laboratory of Carcinogenesis of Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, 410078, China.,Key Laboratory of Information System Engineering, National University of Defense Technology, Changsha, 410073, China
| | - LiLi Huang
- Key Laboratory of Carcinogenesis of Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, 410078, China
| | - MengXi Sun
- Key Laboratory of Carcinogenesis of Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, 410078, China
| | - QiJia Yan
- Key Laboratory of Carcinogenesis of Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, 410078, China
| | - YaLi Song
- Key Laboratory of Carcinogenesis of Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, 410078, China
| | - Fang Wei
- Key Laboratory of Carcinogenesis of Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, 410078, China
| | - Hao Bo
- Key Laboratory of Carcinogenesis of Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, 410078, China
| | - ZhaoJian Gong
- Key Laboratory of Carcinogenesis of Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, 410078, China
| | - Yong Zeng
- Hunan Provincial Tumor Hospital, Xiangya School of Medicine, Central South University, Changsha, 410013, China
| | - Qiao Li
- Key Laboratory of Carcinogenesis of Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, 410078, China
| | - WenLing Zhang
- Key Laboratory of Carcinogenesis of Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, 410078, China
| | - XiaYu Li
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, 410013, China
| | - Bo Xiang
- Key Laboratory of Carcinogenesis of Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, 410078, China
| | - XiaoLing Li
- Key Laboratory of Carcinogenesis of Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, 410078, China
| | - Yong Li
- Department of Biochemistry and Molecular Biology and Center for Genetics and Molecular Medicine, School of Medicine, University of Louisville, Louisville, KY, 40202, USA
| | - Wei Xiong
- Hunan Provincial Tumor Hospital, Xiangya School of Medicine, Central South University, Changsha, 410013, China. .,Key Laboratory of Carcinogenesis of Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, 410078, China. .,Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, 410013, China.
| | - GuiYuan Li
- Hunan Provincial Tumor Hospital, Xiangya School of Medicine, Central South University, Changsha, 410013, China. .,Key Laboratory of Carcinogenesis of Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, 410078, China. .,Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, 410013, China.
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29
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Camargo MC, Kim WH, Chiaravalli AM, Kim KM, Corvalan AH, Matsuo K, Yu J, Sung JJY, Herrera-Goepfert R, Meneses-Gonzalez F, Kijima Y, Natsugoe S, Liao LM, Lissowska J, Kim S, Hu N, Gonzalez CA, Yatabe Y, Koriyama C, Hewitt SM, Akiba S, Gulley ML, Taylor PR, Rabkin CS. Improved survival of gastric cancer with tumour Epstein-Barr virus positivity: an international pooled analysis. Gut 2014; 63:236-43. [PMID: 23580779 PMCID: PMC4384434 DOI: 10.1136/gutjnl-2013-304531] [Citation(s) in RCA: 289] [Impact Index Per Article: 26.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND OBJECTIVE About 9% of gastric carcinomas have Epstein-Barr virus (EBV) in the tumour cells, but it is unclear whether viral presence influences clinical progression. We therefore examined a large multicentre case series for the association of tumour EBV status with survival after gastric cancer diagnosis, accounting for surgical stage and other prognostic factors. METHODS We combined individual-level data on 4599 gastric cancer patients diagnosed between 1976 and 2010 from 13 studies in Asia (n=8), Europe (n=3), and Latin America (n=2). EBV positivity of tumours was assessed by in situ hybridisation. Mortality HRs for EBV positivity were estimated by Cox regression models stratified by study, adjusted for distributions of sex (71% male), age (mean 58 years), stage (52% tumour-node-metastasis stages III or IV), tumour histology (49% poorly differentiated, 57% Lauren intestinal-type), anatomic subsite (70% non-cardia) and year of diagnosis. Variations by study and continent were assessed using study-specific HRs for EBV positivity. RESULTS During median 3.0 years follow-up, 49% of patients died. Stage was strongly predictive of mortality, with unadjusted HRs (vs stage I) of 3.1 for stage II, 8.1 for stage III and 13.2 for stage IV. Tumour EBV positivity was 8.2% overall and inversely associated with stage (adjusted OR: 0.79 per unit change). Adjusted for stage and other confounders, EBV positivity was associated with lower mortality (HR, 0.72; 95% CI 0.61 to 0.86), with low heterogeneity among the study populations (p=0.2). The association did not significantly vary across patient or tumour characteristics. There was no significant variation among the three continent-specific HRs (p=0.4). CONCLUSIONS Our findings suggest that tumour EBV positivity is an additional prognostic indicator in gastric cancer. Further studies are warranted to identify the mechanisms underlying this protective association.
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Affiliation(s)
- M Constanza Camargo
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA
| | - Woo-Ho Kim
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
| | | | - Kyoung-Mee Kim
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Alejandro H Corvalan
- Department of Hematology and Oncology, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Keitaro Matsuo
- Division of Molecular Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan
| | - Jun Yu
- Department of Medicine and Therapeutics, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
| | - Joseph J Y Sung
- Department of Medicine and Therapeutics, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
| | | | - Fernando Meneses-Gonzalez
- Programa de Residencia en Epidemiología, Dirección General Adjunta de Epidemiología, Secretaría de Salud, México City, México
| | - Yuko Kijima
- Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Shoji Natsugoe
- Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Linda M Liao
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA
| | - Jolanta Lissowska
- Division of Cancer Epidemiology and Prevention, M Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland
| | - Sung Kim
- Division of Cancer Epidemiology and Prevention, M Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland
| | - Nan Hu
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA
| | - Carlos A Gonzalez
- Unit of Nutrition, Environment and Cancer, Epidemiology Research Program, Catalan Institute of Oncology, Barcelona, Spain; on behalf of the Euro-gast EPIC study
| | - Yashushi Yatabe
- Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Chihaya Koriyama
- Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Stephen M Hewitt
- Tissue Array Research Program and Applied Molecular Pathology Laboratory, Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland, USA
| | - Suminori Akiba
- Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Margaret L Gulley
- Department of Pathology and Laboratory Medicine, The Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Philip R Taylor
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA
| | - Charles S Rabkin
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA
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Guo H, Wang T, Su HX. Epstein-Barr virus and gastric cancer. Shijie Huaren Xiaohua Zazhi 2013; 21:1616-1622. [DOI: 10.11569/wcjd.v21.i17.1616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer ranks second among malignancies in terms of global incidence. Epstein-Barrvirus (EBV)-associated gastric carcinoma (EBVaGC) is a recently recognized entity, which is defined by the presence of EBV in gastric carcinoma cells. EBVaGC represents about 10% of gastric carcinoma cases worldwide. It is estimated that there are over 80000 new EBVaGC cases in the world annually. EBVaGC shows some distinct clinical and pathological characteristics. The observation that EBV-encoded small RNA is expressed in cancer cells but not in surrounding normal epithelial cells strongly suggests that EBV plays an etiological role in gastric carcinogenesis. In this review, we discuss the relationship between EBV and gastric carcinogenesis.
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Jiang C. Translational medicine in China I: perspectives from Chinese physicians and scientists. SCIENCE CHINA-LIFE SCIENCES 2012; 54:1071-3. [PMID: 22227895 PMCID: PMC7099172 DOI: 10.1007/s11427-011-4260-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/20/2011] [Indexed: 12/11/2022]
Affiliation(s)
- ChengYu Jiang
- Department of Biochemistry and Molecular Biology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005 China
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Camargo MC, Murphy G, Koriyama C, Pfeiffer RM, Kim WH, Herrera-Goepfert R, Corvalan AH, Carrascal E, Abdirad A, Anwar M, Hao Z, Kattoor J, Yoshiwara-Wakabayashi E, Eizuru Y, Rabkin CS, Akiba S. Determinants of Epstein-Barr virus-positive gastric cancer: an international pooled analysis. Br J Cancer 2011; 105:38-43. [PMID: 21654677 PMCID: PMC3137422 DOI: 10.1038/bjc.2011.215] [Citation(s) in RCA: 136] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Revised: 05/10/2011] [Accepted: 05/15/2011] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Meta-analyses of the published literature indicate that about 9% of gastric cancers contain Epstein-Barr virus (EBV), with consistent and significant differences by sex and anatomic subsite. This study aimed to identify additional determinants of EBV positivity and their joint effects. METHODS From 15 international populations with consistent laboratory testing for EBV, we pooled individual-level data for 5081 gastric cancer cases including information on age, sex, subsite, histologic type, diagnostic stage, geographic region, and period of diagnosis. First, we combined population-specific EBV prevalence estimates using random effects meta-analysis. We then aggregated individual-level data to estimate odds ratios of EBV positivity in relation to all variables, accounting for within-population clustering. RESULTS In unadjusted analyses, EBV positivity was significantly higher in males, young subjects, non-antral subsites, diffuse-type histology, and in studies from the Americas. Multivariable analyses confirmed significant associations with histology and region. Sex interacted with age (P=0.003) and subsite (P=0.002) such that male predominance decreased with age for both subsites. The positivity of EBV was not significantly associated with either stage or time period. CONCLUSION Aggregating individual-level data provides additional information over meta-analyses. Distinguishing histologic and geographic features as well as interactions among age, sex, and subsite further support classification of EBV-associated gastric cancer as a distinct aetiologic entity.
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Affiliation(s)
- M C Camargo
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 6120 Executive Boulevard., Rockville, MD 20852, USA.
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