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Zhang T, Zhang Y, Leng X. Trends in gastric cancer burden in the Western Pacific region from 1990 to 2021 and projections to 2040. Front Oncol 2025; 15:1506479. [PMID: 40144216 PMCID: PMC11936811 DOI: 10.3389/fonc.2025.1506479] [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: 10/05/2024] [Accepted: 02/21/2025] [Indexed: 03/28/2025] Open
Abstract
Background Gastric cancer (GC) is a major public health concern, particularly in the Western Pacific, a high-incidence region that bears significant economic and social burdens. Methods Based on data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021, we conducted a comprehensive analysis of trends in the burden of GC in the Western Pacific from 1990 to 2021. We compared these trends with global and World Health Organization regional patterns, with a particular focus on geographic, gender, and age disparities. Health inequality was analyzed by comparing countries with different Socio-demographic Index (SDI) levels. Future trends in age-standardized rates were projected using the Bayesian Age-Period-Cohort (BAPC) model. Results The GC burden of Western Pacific region remains above the global average, but improvements have outpaced global trends. China carries the highest burden, accounting for over half of regional cases, deaths, and disability-adjusted life years. While South Korea and Japan also experience high burdens, they have achieved notable reductions. Males consistently face higher burdens across age groups. Health inequality analysis shows narrowing gaps between high- and low-SDI countries, with the burden shifting toward less developed nations. BAPC model projections indicate a further decline in the GC burden by 2040. Conclusion Despite substantial progress in countries like Japan and South Korea, continued focus is needed on less developed regions to reduce the remaining GC burden in the future.
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Affiliation(s)
- Tao Zhang
- Department of Gastric and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Yiqun Zhang
- Department of Gynecology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China
- State Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Medical University, Chongqing, China
- Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China
| | - Xiaofei Leng
- Department of Gynecology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China
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Ou L, Liu H, Peng C, Zou Y, Jia J, Li H, Feng Z, Zhang G, Yao M. Helicobacter pylori infection facilitates cell migration and potentially impact clinical outcomes in gastric cancer. Heliyon 2024; 10:e37046. [PMID: 39286209 PMCID: PMC11402937 DOI: 10.1016/j.heliyon.2024.e37046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 08/23/2024] [Accepted: 08/27/2024] [Indexed: 09/19/2024] Open
Abstract
Gastric cancer is a significant health concern worldwide. Helicobacter pylori (HP) infection is associated with gastric cancer risk, but differences between HP-infected and HP-free gastric cancer have not been studied sufficiently. The objective of this study was to investigate the effects of HP infection on the viability and migration of gastric cancer cells and identify potential underlying genetic mechanisms as well as their clinical relevance. Cell counting kit-8, lactate dehydrogenase, wound healing, and transwell assay were applied in the infection model of multiple clones of HP and multiple gastric cancer cell lines. Genes related to HP infection were identified using bioinformatics analysis and subsequently validated using real-time quantitative PCR. The association of these genes with immunity and drug sensitivity of gastric cancer was analyzed. Results showed that HP has no significant impact on viability but increases the migration of gastric cancer cells. We identified 1405 HP-upregulated genes, with their enriched terms relating to cell migration, drug, and immunity. Among these genes, the 82 genes associated with survival showed a significant impact on gastric cancer in consensus clustering and LASSO prognostic model. The top 10 hub HP-associated genes were further identified, and 7 of them were validated in HP-infected cells using real-time quantitative PCR, including ERBB4, DNER, BRINP2, KCTD16, MAPK4, THPO, and VSTM2L. The overexpression experiment showed that KCTD16 medicated the effect of HP on gastric cancer migration. Our findings suggest that HP infection may enhance the migratory potential of gastric cancer cells and these genes might be associated with immunity and drug sensitivity of gastric cancer. In human subjects with gastric cancer, HP presence in tumors may affect migration, immunity, and drug sensitivity.
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Affiliation(s)
- Ling Ou
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China
| | - Hengrui Liu
- Cancer Institute, Jinan University, Guangzhou, China
- Tianjin Yinuo Biomedical Co., Ltd, Tianjin, China
| | - Chang Peng
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China
| | - Yuanjing Zou
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China
| | - Junwei Jia
- International Pharmaceutical Engineering Lab of Shandong Province, Feixian, 273400, Shandong, China
| | - Hui Li
- International Pharmaceutical Engineering Lab of Shandong Province, Feixian, 273400, Shandong, China
| | - Zhong Feng
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China
- International Pharmaceutical Engineering Lab of Shandong Province, Feixian, 273400, Shandong, China
| | - Guimin Zhang
- Lunan Pharmaceutical Group Co., Ltd, Linyi, 276000, Shandong, China
| | - Meicun Yao
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China
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Lee HK, Shin CM, Chang YH, Yoon H, Park YS, Kim N, Lee DH. Gastric microbiome signature for predicting metachronous recurrence after endoscopic resection of gastric neoplasm. Gastric Cancer 2024; 27:1031-1045. [PMID: 38970748 DOI: 10.1007/s10120-024-01532-3] [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: 03/26/2024] [Accepted: 06/29/2024] [Indexed: 07/08/2024]
Abstract
BACKGROUND Changes in gastric microbiome are associated with gastric carcinogenesis. Studies on the association between gastric mucosa-associated gastric microbiome (MAM) and metachronous gastric cancer are limited. This study aimed to identify gastric MAM as a predictive factor for metachronous recurrence following endoscopic resection of gastric neoplasms. METHOD Microbiome analyses were conducted for 81 patients in a prospective cohort to investigate surrogate markers to predict metachronous recurrence. Gastric MAM in non-cancerous corporal biopsy specimens was evaluated using Illumina MiSeq platform targeting 16S ribosomal DNA. RESULTS Over a median follow-up duration of 53.8 months, 16 metachronous gastric neoplasms developed. Baseline gastric MAM varied with Helicobacter pylori infection status, but was unaffected by initial pathologic diagnosis, presence of atrophic gastritis, intestinal metaplasia, or synchronous lesions. The group with metachronous recurrence did not exhibit distinct phylogenetic diversity compared with the group devoid of recurrence but showed significant difference in β-diversity. The study population could be classified into two distinct gastrotypes based on baseline gastric MAM: gastrotype 1, Helicobacter-abundant; gastrotype 2: Akkermansia-abundant. Patients in gastrotype 2 showed higher risk of metachronous recurrence than gastrotype (Cox proportional hazard analysis, adjusted hazard ratio [95% confidence interval]: 5.10 [1.09-23.79]). CONCLUSIONS Gastric cancer patients can be classified into two distinct gastrotype groups by their MAM profiles, which were associated with different risk of metachronous recurrence.
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Affiliation(s)
- Ho-Kyoung Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam-Si, Gyeonggi-Do, 13620, South Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam-Si, Gyeonggi-Do, 13620, South Korea.
| | - Young Hoon Chang
- Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam-Si, Gyeonggi-Do, 13620, South Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam-Si, Gyeonggi-Do, 13620, South Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam-Si, Gyeonggi-Do, 13620, South Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam-Si, Gyeonggi-Do, 13620, South Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam-Si, Gyeonggi-Do, 13620, South Korea
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Kotelevets SM, Chekh SA, Chukov SZ. Effectiveness of serological markers of gastric mucosal atrophy in the gastric precancer screening and in cancer prevention. World J Gastrointest Endosc 2024; 16:462-471. [PMID: 39155993 PMCID: PMC11325870 DOI: 10.4253/wjge.v16.i8.462] [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] [Received: 03/13/2024] [Revised: 06/30/2024] [Accepted: 07/25/2024] [Indexed: 08/01/2024] Open
Abstract
BACKGROUND New markers are needed to improve the effectiveness of serological screening for atrophic gastritis. AIM To develop a cost-effective method for serological screening of atrophic gastritis with a high level of sensitivity. METHODS Of the 169 patients with atrophic gastritis, selected by the visual endoscopic Kimura-Takemoto method, 165 showed histological mucosal atrophy using the updated Kimura-Takemoto method. All 169 patients were examined for postprandial levels of gastrin-17 (G17) and pepsinogen-1 (PG1) using GastroPanel® (Biohit Plc, Helsinki, Finland). RESULTS We used the histological standard of five biopsies of the gastric mucosa, in accordance with the Kimura-Takemoto classification system to assess the sensitivity of G17 in detecting gastric mucosal atrophy. We also compared the morpho-functional relationships between the detected histological degree of gastric mucosal atrophy and the serological levels of G17 and PG1, as the markers of atrophic gastritis. The sensitivity of postprandial G17 was 62.2% for serological levels of G17 (range: 0-4 pmol/L) and 100% for serological G17 (range: 0-10 pmol/L) for the detection of monofocal severe atrophic gastritis. No strong correlation was found between the levels of PG1 and degree of histological atrophy determined by the Kimura-Takemoto classification system to identify the severity of mucosal atrophy of the gastric corpus. In the presented clinical case of a 63-year-old man with multifocal atrophic gastritis, there is a pronounced positive long-term dynamics of the serological marker of atrophy - postprandial G17, after five months of rennet replacement therapy. CONCLUSION Serological screening of multifocal atrophic gastritis by assessment of postprandial G17 is a cost-effective method with high sensitivity. Postprandial G17 is an earlier marker of regression of atrophic gastritis than a morphological examination of a gastric biopsy in accordance with the Sydney system. Therefore, postprandial G17 is recommended for dynamic monitoring of atrophic gastritis after treatment.
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Affiliation(s)
- Sergey M Kotelevets
- Department of Therapy, North Caucasus State Academy, Cherkessk 369000, Karachay-Cherkess Republic, Russia
| | - Sergey A Chekh
- Department of Mathematics, North Caucasus State Academy, Cherkessk 369000, Karachay-Cherkess Republic, Russia
| | - Sergey Z Chukov
- Department of Pathological Anatomy, Stavropol State Medical University, Stavropol 355017, Russia
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Hatta W, Koike T, Asano N, Hatayama Y, Ogata Y, Saito M, Jin X, Uno K, Imatani A, Masamune A. The Impact of Tobacco Smoking and Alcohol Consumption on the Development of Gastric Cancers. Int J Mol Sci 2024; 25:7854. [PMID: 39063094 PMCID: PMC11276971 DOI: 10.3390/ijms25147854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Revised: 07/09/2024] [Accepted: 07/12/2024] [Indexed: 07/23/2024] Open
Abstract
Chronic infection of Helicobacter pylori is considered the principal cause of gastric cancers, but evidence has accumulated regarding the impact of tobacco smoking and alcohol consumption on the development of gastric cancers. Several possible mechanisms, including the activation of nicotinic acetylcholine receptors, have been proposed for smoking-induced gastric carcinogenesis. On the other hand, local acetaldehyde exposure and ethanol-induced mucosal inflammation have been proposed as the mechanisms involved in the development of gastric cancers in heavy alcohol drinkers. In addition, genetic polymorphisms are also considered to play a pivotal role in smoking-related and alcohol-related gastric carcinogenesis. In this review, we will discuss the molecular mechanisms involved in the development of gastric cancers in relation to tobacco smoking and alcohol consumption.
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Affiliation(s)
- Waku Hatta
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Miyagi, Japan; (T.K.); (Y.H.); (Y.O.); (M.S.); (X.J.); (K.U.); (A.I.); (A.M.)
| | - Tomoyuki Koike
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Miyagi, Japan; (T.K.); (Y.H.); (Y.O.); (M.S.); (X.J.); (K.U.); (A.I.); (A.M.)
| | - Naoki Asano
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Miyagi, Japan; (T.K.); (Y.H.); (Y.O.); (M.S.); (X.J.); (K.U.); (A.I.); (A.M.)
- Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, 47-1 Nodayama, Medeshima-Shiode, Natori 981-1293, Miyagi, Japan
- Division of Carcinogenesis and Senescence Biology, Tohoku University Graduate School of Medicine, Natori 981-1293, Miyagi, Japan
| | - Yutaka Hatayama
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Miyagi, Japan; (T.K.); (Y.H.); (Y.O.); (M.S.); (X.J.); (K.U.); (A.I.); (A.M.)
| | - Yohei Ogata
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Miyagi, Japan; (T.K.); (Y.H.); (Y.O.); (M.S.); (X.J.); (K.U.); (A.I.); (A.M.)
| | - Masahiro Saito
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Miyagi, Japan; (T.K.); (Y.H.); (Y.O.); (M.S.); (X.J.); (K.U.); (A.I.); (A.M.)
| | - Xiaoyi Jin
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Miyagi, Japan; (T.K.); (Y.H.); (Y.O.); (M.S.); (X.J.); (K.U.); (A.I.); (A.M.)
| | - Kaname Uno
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Miyagi, Japan; (T.K.); (Y.H.); (Y.O.); (M.S.); (X.J.); (K.U.); (A.I.); (A.M.)
| | - Akira Imatani
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Miyagi, Japan; (T.K.); (Y.H.); (Y.O.); (M.S.); (X.J.); (K.U.); (A.I.); (A.M.)
| | - Atsushi Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Miyagi, Japan; (T.K.); (Y.H.); (Y.O.); (M.S.); (X.J.); (K.U.); (A.I.); (A.M.)
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Gao C, Zhang G, Zheng J, Zheng Y, Lin W, Xu G, You Y, Li D, Wang W. The value of LCI-based modified Kyoto classification risk scoring system in predicting the risk of early gastric cancer. Scand J Gastroenterol 2024; 59:859-867. [PMID: 38578144 DOI: 10.1080/00365521.2024.2338443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 03/21/2024] [Accepted: 03/29/2024] [Indexed: 04/06/2024]
Abstract
OBJECTIVE To study and compare the value of the Kyoto classification risk scoring system and the modified Kyoto classification risk scoring system based on linked color imaging (LCI) in predicting the risk of early gastric cancer. METHODS One hundred and fifty patients with pathologically confirmed non-cardia early gastric cancer by endoscopic LCI and 150 non-gastric cancer patients matched for age and gender were included. Basic patient data and whole gastric endoscopic images under LCI were collected, and the images were scored according to the LCI-based Kyoto classification risk scoring system and the LCI-based modified Kyoto classification risk scoring system. RESULTS Compared with the LCI-based Kyoto classification risk scoring system, the LCI-based modified Kyoto classification risk scoring system had a higher AUC for predicting the risk of early gastric cancer (0.723 vs. 0.784, p = 0.023), with a score of ≥3 being the best cutoff value for predicting the risk of early gastric cancer (sensitivity 61.33%, specificity 86.00%), and scores of 3 to 5 were significantly associated with early gastric carcinogenesis significantly (OR = 9.032, 95% CI: 4.995-16.330, p < 0.001). CONCLUSIONS Compared with the LCI-based Kyoto classification risk scoring system, the LCI-based Kyoto modified classification risk scoring system has a better value for predicting the risk of early gastric cancer, and the score of 3 to 5 is a high-risk factor for the risk of early gastric cancer development, which is more strongly correlated with the risk of early gastric cancer.
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Affiliation(s)
- Chao Gao
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, Fujian Medical University, Fuzhou, China
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, People's Liberation Army, Fuzhou, China
| | - Guanpo Zhang
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, Fujian Medical University, Fuzhou, China
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, People's Liberation Army, Fuzhou, China
| | - Jin Zheng
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, Fujian Medical University, Fuzhou, China
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, People's Liberation Army, Fuzhou, China
| | - Yunmeng Zheng
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, Fujian Medical University, Fuzhou, China
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, People's Liberation Army, Fuzhou, China
| | - Wulian Lin
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, Fujian Medical University, Fuzhou, China
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, People's Liberation Army, Fuzhou, China
| | - Guilin Xu
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, Fujian Medical University, Fuzhou, China
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, People's Liberation Army, Fuzhou, China
| | - Yixiang You
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, Fujian Medical University, Fuzhou, China
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, People's Liberation Army, Fuzhou, China
| | - Dazhou Li
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, Fujian Medical University, Fuzhou, China
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, People's Liberation Army, Fuzhou, China
| | - Wen Wang
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, Fujian Medical University, Fuzhou, China
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, People's Liberation Army, Fuzhou, China
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Li Y, Hahn AI, Laszkowska M, Jiang F, Zauber AG, Leung WK. Global burden of young-onset gastric cancer: a systematic trend analysis of the global burden of disease study 2019. Gastric Cancer 2024; 27:684-700. [PMID: 38570392 PMCID: PMC11193827 DOI: 10.1007/s10120-024-01494-6] [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: 10/03/2023] [Accepted: 03/13/2024] [Indexed: 04/05/2024]
Abstract
BACKGROUND While gastric cancer is generally declining globally, the temporal trend of young-onset (< 40 years) gastric cancer remains uncertain. We performed this analysis to determine the temporal trends of young-onset gastric cancer compared to late-onset cancer (≥ 40 years). METHODS We extracted cross-sectional data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. The burden of gastric cancer from 1990 to 2019 was assessed through indicators including incidence and mortality rates, which were classified at global, national, and regional levels, and according to socio-demographic indexes (SDI) and age or sex groups. Joinpoint regression analysis was used to identify specific years with significant changes. The correlation between AAPC with countries' average SDI was tested by Pearson's Test. RESULTS The global incidence rate of young-onset gastric cancer decreased from 2.20 (per 100,000) in 1990 to 1.65 in 2019 (AAPC: - 0.95; 95% confidence interval [CI] - 1.25 to - 0.65; P < 0.001). Late-onset cancer incidence also decreased from 59.53 (per 100,000) in 1990 to 41.26 in 2019 (AAPC: - 1.23; 95% CI - 1.39 to - 1.06, P < 0.001). Despite an overall decreasing trend, the incidence rate of young-onset cancer demonstrated a significant increase from 2015 to 2019 (annual percentage change [APC]: 1.39; 95% CI 0.06 to 2.74; P = 0.041), whereas no upward trend was observed in late-onset cancer. Mortality rates of young- and late-onset cancer both exhibited a significant decline during this period (AAPC: - 1.82; 95% CI - 2.15 to - 1.56; P < 0.001 and AAPC: - 1.69, 95% CI - 1.79 to - 1.59; P < 0.001). The male-to-female rate ratio for incidence and mortality in both age groups have been increasing since 1990. While countries with high SDI have had a greater decline in the incidence of late-onset gastric cancer (slope of AAPC change: - 0.20, P = 0.004), it was not observed in young-onset cancer (slope of AAPC change: - 0.11, P = 0.13). CONCLUSIONS The global incidence and mortality rates of both young- and late-onset gastric cancer have decreased since 1990. However, the incidence rate of young-onset cancer has demonstrated a small but significant upward trend since 2015. There was disparity in the decline in young-onset gastric cancer among male and high SDI countries. These findings could help to inform future strategies in preventing gastric cancer in younger individuals.
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Affiliation(s)
- Yunhao Li
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
| | - Anne I Hahn
- Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Monika Laszkowska
- Gastroenterology, Hepatology, and Nutrition Service, Department of Subspecialty Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Fang Jiang
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
| | - Ann G Zauber
- Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Wai K Leung
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China.
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Kang K, Bagaoisan MA, Zhang Y. Unveiling the Younger Face of Gastric Cancer: A Comprehensive Review of Epidemiology, Risk Factors, and Prevention Strategies. Cureus 2024; 16:e62826. [PMID: 39036206 PMCID: PMC11260356 DOI: 10.7759/cureus.62826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/20/2024] [Indexed: 07/23/2024] Open
Abstract
Gastric cancer poses a significant global health challenge, with high incidence and mortality rates each year. Despite advancements in screening and treatment, late detection remains a critical issue. Efforts to address this include raising public awareness and implementing targeted screening programs for high-risk populations. The increasing incidence of gastric cancer among younger individuals underscores the need for lifestyle adjustments and targeted interventions to mitigate risks and improve outcomes. Understanding the various factors contributing to gastric cancer risk is essential for effective prevention strategies, including Helicobacter pylori eradication, lifestyle modifications, and regular screening for high-risk groups. A comprehensive approach addressing both individual behaviors and broader societal factors is crucial in the fight against gastric cancer. This review provides an in-depth examination of gastric cancer epidemiology, risk factors, preventive measures, and screening initiatives, with a particular focus on the rising incidence among younger demographics. Emphasizing the importance of early detection and intervention, the review highlights the need for proactive screening to improve patient outcomes and reduce mortality rates. By addressing these aspects comprehensively, this paper aims to enhance the understanding of gastric cancer dynamics, particularly its incidence among younger individuals, and to inform future strategies for prevention and control.
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Affiliation(s)
- Kai Kang
- Institute of Nursing, Angeles University Foundation, Angeles City, PHL
| | | | - YuXin Zhang
- Institute of Clinical Nursing, Gansu Health Vocational College, Lanzhou, CHN
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Song DH, Kim N, Jo HH, Kim S, Choi Y, Oh HJ, Lee HS, Yoon H, Shin CM, Park YS, Lee DH, Kang SH, 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, Surh YJ. Analysis of Characteristics and Risk Factors of Patients with Single Gastric Cancer and Synchronous Multiple Gastric Cancer among 14,603 Patients. Gut Liver 2024; 18:231-244. [PMID: 36987384 PMCID: PMC10938156 DOI: 10.5009/gnl220491] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 02/02/2023] [Accepted: 02/20/2023] [Indexed: 03/30/2023] Open
Abstract
Background/Aims Synchronous multiple gastric cancer (SMGC) accounts for approximately 6% to 14% of gastric cancer (GC) cases. This study aimed to identify risk factors for SMGC. Methods A total of 14,603 patients diagnosed with GC were prospectively enrolled. Data including age, sex, body mass index, smoking, alcohol consumption, family history, p53 expression, microsatellite instability, cancer classification, lymph node metastasis, and treatment were collected. Risk factors were analyzed using logistic regression analysis between a single GC and SMGC. Results The incidence of SMGC was 4.04%, and that of early GC (EGC) and advanced GC (AGC) was 5.43% and 3.11%, respectively. Patients with SMGC were older (65.33 years vs 61.75 years, p<0.001) and more likely to be male. Lymph node metastasis was found in 27% of patients with SMGC and 32% of patients with single GC. Multivariate analysis showed that SMGC was associated with sex (male odds ratio [OR], 1.669; 95% confidence interval [CI], 1.223 to 2.278; p=0.001), age (≥65 years OR, 1.532; 95% CI, 1.169 to 2.008; p=0.002), and EGC (OR, 1.929; 95% CI, 1.432 to 2.600; p<0.001). Survival rates were affected by Lauren classification, sex, tumor size, cancer type, distant metastasis, and venous invasion but were not related to the number of GCs. However, the survival rate of AGC with SMGC was very high. Conclusions SMGC had unique characteristics such as male sex, older age, and EGC, and the survival rate of AGC, in which the intestinal type was much more frequent, was very good (Trial registration number: NCT04973631).
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Affiliation(s)
- Du Hyun Song
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Hyeong Ho Jo
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Sangbin Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yonghoon Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyeon Jeong Oh
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hye Seung Lee
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - So Hyun Kang
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Young Suk Park
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Sang-Hoon Ahn
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yun-Suhk Suh
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Do Joong Park
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Hyung Ho Kim
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Ji-Won Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jin Won Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Keun-Wook Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Won Chang
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Ji Hoon Park
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yoon Jin Lee
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Kyoung Ho Lee
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Young Hoon Kim
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Soyeon Ahn
- Division of Statistics, Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Young-Joon Surh
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul, Korea
- Cancer Research Institute, Seoul National University, Seoul, Korea
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10
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Yoo HW, Hong SJ, Kim SH. Helicobacter pylori Treatment and Gastric Cancer Risk After Endoscopic Resection of Dysplasia: A Nationwide Cohort Study. Gastroenterology 2024; 166:313-322.e3. [PMID: 37863270 DOI: 10.1053/j.gastro.2023.10.013] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Revised: 09/21/2023] [Accepted: 10/08/2023] [Indexed: 10/22/2023]
Abstract
BACKGROUND & AIMS The study investigated the association between Helicobacter pylori treatment and the risk of gastric cancer after endoscopic resection of gastric dysplasia. METHODS Patients who received endoscopic resection for gastric dysplasia between 2010 and 2020 from Korean nationwide insurance data were included. We verified the occurrence of new-onset gastric cancer and metachronous gastric neoplasm, which encompasses both cancer and dysplasia, >1 year after the index endoscopic resection. Newly diagnosed gastric cancer ≥3 years and ≥5 years was regarded as late-onset gastric cancer. A multivariable Cox regression model with H pylori treatment status as a time-dependent covariate was used to determine the risk of gastric cancer and metachronous gastric neoplasms. RESULTS Gastric dysplasia in 69,722 patients was treated with endoscopy, and 49.5% were administered H pylori therapy. During the median 5.6 years of follow-up, gastric cancer developed in 2406 patients and metachronous gastric neoplasms developed in 3342 patients. Receiving H pylori therapy was closely related to lower gastric cancer risk (adjusted hazard ratio [aHR], 0.88; 95% confidence interval [CI], 0.80-0.96). H pylori treatment also significantly decreased metachronous gastric neoplasm development (aHR, 0.76; 95% CI, 0.70-0.82). Furthermore, H pylori therapy showed a prominent protective effect for late-onset gastric cancer development at ≥3 years (aHR, 0.84; 95% CI, 0.75-0.94) and ≥5 years (aHR, 0.80; 95% CI, 0.68-0.95). CONCLUSIONS In this nationwide cohort, H pylori therapy after endoscopic resection of gastric dysplasia was associated with a reduced risk of gastric cancer and metachronous gastric neoplasm occurrence.
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Affiliation(s)
- Hae Won Yoo
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soon Chun Hyang University College of Medicine, Bucheon, Korea
| | - Su Jin Hong
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soon Chun Hyang University College of Medicine, Bucheon, Korea.
| | - Shin Hee Kim
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soon Chun Hyang University College of Medicine, Bucheon, Korea
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11
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He Y, Hu L, Qiu W, Zhu L, Zhu X, Hong M. Clinical characteristics and risk factors of Helicobacter pylori infection-associated Sjogren's syndrome. Immun Inflamm Dis 2023; 11:e994. [PMID: 37904694 PMCID: PMC10614117 DOI: 10.1002/iid3.994] [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: 03/26/2023] [Revised: 08/07/2023] [Accepted: 08/16/2023] [Indexed: 11/01/2023] Open
Abstract
OBJECTIVE Although infectious pathogens are predominant factors for inducing and maintaining immune system disorders, there exist few reports establishing the significant correlation between Helicobacter pylori (H. pylori) infection and Sjogren's syndrome. This study aims to demonstrate the correlation between Sjogren's syndrome and H. pylori infection in patients, highlighting various clinical characteristics and risk factors. METHODS A single-center retrospective observational study was conducted in patients (n = 224) admitted from January 1, 2012, to February 10, 2021, in the First Affiliated Hospital of Wenzhou Medical University (Wenzhou, China). All the recruited subjects with Sjogren's syndrome and H. pylori infection were only included by validating the available medical records online. RESULTS In this study, a total of 224 patients from January 1, 2012, to February 10, 2021, were diagnosed with Sjogren's syndrome. Among them, 94 patients (41.96%) with Sjogren's syndrome were infected with H. pylori. Accordingly, the clinical manifestations, serological and immunological characteristics, as well as gastroscopic biopsy outcomes of the recruited patients with primary Sjogren's syndrome (pSS) were reported. The multivariable analysis of the dry syndrome patients infected with H. pylori displayed hypergammaglobulinemia (odds ratio [OR], 0.354; 95% confidence interval [CI], 0.189-0.663), total cholesterol (OR, 1.158; 95% CI, 0.856-1.550), hypertension (OR, 0.227; 95% CI, 0.114-0.455), Female sex (OR, 5.778; 95% CI, 1.458-22.9), anti-SSA/Ro60 positive (OR, 2.384; 95% CI, 233-4.645), γ-GT (OR, 0.99; 95% CI, 0.99-1.00) and alkaline phosphatase (ALP, OR, 1.00; 95% CI, 0.99-1.00) levels. CONCLUSION Together, our findings demonstrated that hypergammaglobulinemia could be the independent risk factors of H. pylori infection in patients with Sjogren's syndrome, requiring the physician's advice in the future.
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Affiliation(s)
- Ye He
- Department of RheumatologyTaizhou Municipal HospitalTaizhouZhejiangPeople's Republic of China
- Department of RheumatologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangPeople's Republic of China
| | - Lingzhen Hu
- Department of RheumatologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangPeople's Republic of China
| | - Wei Qiu
- Department of DermatologicalThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouPeople's Republic of China
| | - Lixia Zhu
- Department of RheumatologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangPeople's Republic of China
| | - Xiaochun Zhu
- Department of RheumatologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangPeople's Republic of China
| | - Mingzhi Hong
- Department of Burn and Plastic SurgeryTaizhou Municipal HospitalTaizhouZhejiangPeople's Republic of China
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12
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Xie B, Xia Y, Wang X, Xiong Y, Chen SB, Zhang J, He WW. Factors associated with heterochronic gastric cancer development post-endoscopic mucosal dissection in early gastric cancer patients. World J Gastrointest Oncol 2023; 15:1644-1652. [PMID: 37746653 PMCID: PMC10514730 DOI: 10.4251/wjgo.v15.i9.1644] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 08/09/2023] [Accepted: 08/21/2023] [Indexed: 09/13/2023] Open
Abstract
BACKGROUND Endoscopic mucosal resection is an innovative method for treating early gastric cancer and has been widely used in clinical practice. AIM To analyze the factors associated with the development of heterochronic gastric cancer in patients with early gastric cancer who had undergone endoscopic mucosal dissection (EMD). METHODS A cohort of patients with early gastric cancer treated using EMD was retrospectively analyzed, and patients who developed heterochronic gastric cancer after the surgery were compared with those who did not. The effects of patient age, sex, tumor size, pathological type, and surgical technique on the development of heterochronic gastric cancer were assessed using statistical analysis. RESULTS Of the 300 patients with early gastric cancer, 150 patients developed heterochronic gastric cancer after EMD. Statistical analysis revealed that patient age (P value = XX), sex (P value = XX), tumor size (P value = XX), pathological type (P value = XX), and surgical technique (P value = XX) were significantly associated with the occurrence of heterochronic gastric cancer. CONCLUSION Age, sex, tumor size, pathological type, and surgical technique are key factors influencing the occurrence of heterochronic gastric cancer after EMD in patients with early gastric cancer. To address these factors, postoperative follow-up and management should be strengthened to improve the prognosis and survival rate of patients.
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Affiliation(s)
- Bing Xie
- Department of Spleen and Stomach, Nanjing Pu Kou District Hospital of Traditional Chinese Medicine, Pukou 210000, Jiangsu Province, China
| | - Yun Xia
- Department of Spleen and Stomach, Nanjing Pu Kou District Hospital of Traditional Chinese Medicine, Pukou 210000, Jiangsu Province, China
| | - Xia Wang
- Department of Spleen and Stomach, Nanjing Pu Kou District Hospital of Traditional Chinese Medicine, Pukou 210000, Jiangsu Province, China
| | - Yan Xiong
- Science and Education Section, Nanjing Pu Kou District Hospital of Traditional Chinese Medicine, Pukou 210000, Jiangsu Province, China
| | - Shao-Bo Chen
- Anesthesiology Department, Nanjing Pu Kou District Hospital of Traditional Chinese Medicine, Pukou 210000, Jiangsu Province, China
| | - Jie Zhang
- Department of Spleen and Stomach, Nanjing Pu Kou District Hospital of Traditional Chinese Medicine, Pukou 210000, Jiangsu Province, China
| | - Wei-Wei He
- Department of Oncology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, Jiangsu Province, China
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13
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Chen Z, Zheng Y, Fan P, Li M, Liu W, Yuan H, Liu X, Zhang Z, Wu Z, Wang Y, Ji R, Guo Q, Ye Y, Zhang J, Li X, An F, Lu L, Li Y, Wang X, Zhang J, Guan Q, Li Q, Liu M, Ren Q, Hu X, Lu H, Zhang H, Zhao Y, Gou X, Shu X, Wang J, Hu Z, Xue S, Liu J, Zhou Y. Risk factors in the development of gastric adenocarcinoma in the general population: A cross-sectional study of the Wuwei Cohort. Front Microbiol 2023; 13:1024155. [PMID: 36713177 PMCID: PMC9878447 DOI: 10.3389/fmicb.2022.1024155] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Accepted: 12/16/2022] [Indexed: 01/13/2023] Open
Abstract
Several risk factors have been identified for the development of gastric adenocarcinoma (GAC), where the control group was usually a healthy population. However, it is unclear at what stage known risk factor exert their influence toward the progression to cancer. Based on the Wuwei Cohort, we enrolled 1,739 patients with chronic non-atrophic gastritis (no-CAG), 3,409 patients with chronic atrophic gastritis (CAG), 1,757 patients with intestinal metaplasia (IM), 2,239 patients with low-grade dysplasia (LGD), and 182 patients with high-grade dysplasia (HGD) or GAC to assess the risk factors between each two consecutive stages from no-CAG to GAC/HGD using adjusted logistic regression. We found that different groups of risk factors were associated with different stages. Age, occupation of farmer, low annual family income, Helicobacter pylori (H. pylori) infection, drinking, eating hot food, histories of gastritis and peptic ulcer were associated with the development of CAG. Age, illiteracy, H. pylori infection, smoking, eating hot food, eating quickly, and histories of gastritis and gallbladder diseases were associated with the progression to IM from CAG. Male, occupation of farmer and history of peptic ulcer were associated with the development of LGD from IM. Age, male and polyp history appeared to be risk factors associated with the development of GAC/HGD from LGD. In conclusion, it seems that most risk factors function more as a set of switches that initiated the GAC carcinogenesis. H. Pylori eradication and control of other risk factors should be conducted before IM to decrease the incidence of GAC.
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Affiliation(s)
- Zhaofeng Chen
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Ya Zheng
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Ping Fan
- Gansu Wuwei Tumor Hospital, Wuwei, Gansu, China
| | - Min Li
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China
| | - Wei Liu
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China
| | - Hao Yuan
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Xin Liu
- Department of Gastroenterology, The 940th Hospital of Joint Service Logistics Support Force of Chinese People's Liberation Army, Lanzhou, Gansu, China
| | - Zhiyi Zhang
- Gansu Wuwei Tumor Hospital, Wuwei, Gansu, China
| | - Zhengqi Wu
- Gansu Wuwei Tumor Hospital, Wuwei, Gansu, China
| | - Yuping Wang
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Rui Ji
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Qinghong Guo
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Yuwei Ye
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Jinhua Zhang
- Gansu Second Provincial People’s Hospital, Lanzhou, Gansu, China
| | - Xiaohua Li
- Wuwei Liangzhou Hospital, Wuwei, Gansu, China
| | - Feng An
- Wuwei People's Hospital, Wuwei, Gansu, China
| | - Linzhi Lu
- Gansu Wuwei Tumor Hospital, Wuwei, Gansu, China
| | - Youpeng Li
- Minqin People's Hospital, Minqin, Gansu, China
| | - Xiang Wang
- Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Jun Zhang
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Quanlin Guan
- Surgical Oncology Department, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Qiang Li
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Min Liu
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Qian Ren
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Xiaobin Hu
- School of Public Health, Lanzhou University, Lanzhou, Gansu, China
| | - Hong Lu
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Hongling Zhang
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Yue Zhao
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Xi Gou
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Xiaochuang Shu
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Jun Wang
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Zenan Hu
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Siqian Xue
- Interventional Radiology Department, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Jiankang Liu
- Harvard Medical School, Cardiovascular Division, Brigham and Women’s Hospital, Boston, MA, United States
| | - Yongning Zhou
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, Gansu, China,*Correspondence: Yongning Zhou, ✉
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14
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Choi S, Kim N, Park JH, Nam RH, Song CH, Lee HS. Effect of Helicobacter pylori infection and its eradication on the expression of tight junction proteins in the gastric epithelium in relation to gastric carcinogenesis. Helicobacter 2022; 27:e12929. [PMID: 36063450 DOI: 10.1111/hel.12929] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 08/10/2022] [Accepted: 08/15/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND Tight junction proteins (TJPs) play a role in epithelial defense mechanisms. However, the effect of Helicobacter pylori (Hp) on TJPs remains unclear. This study aimed to evaluate the expression of TJPs in relation to Hp infection and eradication in gastric carcinogenesis. METHODS In total, 510 subjects (284 controls and 226 gastric cancer [GC] patients) were prospectively enrolled in the study. The expression of claudin-1 and -2 (CLDN-1, -2), occludin (OCLN), and tight junction protein 1 (TJP1) was measured based on their Hp infection status in normal corpus mucosa and evaluated following Hp eradication using quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry (IHC). RESULTS The expression of TJP1 in Hp+ controls was significantly lower than that in Hp- controls (p = 0.006), whereas it was higher in Hp+ than in Hp- GC patients (p = 0.001). Moreover, the increased expression of TJP1 in Hp+ GC patients was reduced to levels in Hp- within a year after Hp eradication and was maintained for more than 5 years. Furthermore, IHC results for TJP1 were similar to qPCR results. In particular, the higher IHC staining intensity of TJP1 in the cytosol of GC patients (p = 0.019) decreased after Hp eradication (p = 0.040). CONCLUSION Hp infection affects TJP expression. The high expression of TJP1 in Hp+ GC patients was restored to control levels after Hp eradication, suggesting that TJP1 plays a role in gastric carcinogenesis.
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Affiliation(s)
- SooIn Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University, Seoul, South Korea
| | - Ji Hyun Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University, Seoul, South Korea
| | - Ryoung Hee Nam
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Chin-Hee Song
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Hye Seung Lee
- Department of Pathology, Seoul National University, Seoul, South Korea
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15
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García-Gómez-Heras S, Fernández-Aceñero MJ, González G, Bolaños-Muñoz MDL, Franco-Rodríguez R, Paredes-González J, Ruiz-Tovar J. Involvement of Helicobacter pylori in Preoperative Gastric Findings on a Bariatric Population. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:9088. [PMID: 35897458 PMCID: PMC9332016 DOI: 10.3390/ijerph19159088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 07/16/2022] [Accepted: 07/22/2022] [Indexed: 11/16/2022]
Abstract
The prevalence of Helicobacter pylori (Hp) in bariatric patients is common and related to gastric pathology. With preoperative upper gastrointestinal endoscopy (UGE), these pathologies and the presence of Hp are diagnosed. The histopathological study of the UGE biopsies is classified based on the Sydney System, a scoring system that stages chronic gastritis (CG) and precancerous gastric lesions. The objective is to assess the histological findings of gastric biopsies during routine UGE and to determine the involvement of Hp in gastric disorders in patients undergoing bariatric surgery. A multicenter retrospective review of prospectively collected databases was performed. The presence of CG, gastric atrophy (GA), and gastric intestinal metaplasia (GIM) in the study of the biopsies was assessed and correlated with Hp infection. The incidence of Hp among our bariatric population was 36.1%, and it increases with age. The percentage of patients with severe Hp infection is higher in patients with GA or GIM. The Hp eradication rate is also reduced when GA and GIM are present. A histological examination of all the biopsies did not show features of malignancy in any of the cases. Hp is not the only factor involved in the development of gastric pathology in bariatric patients.
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Affiliation(s)
- Soledad García-Gómez-Heras
- Department of Basic Health Science, Health Science Faculty, Rey Juan Carlos University, 28922 Madrid, Spain; (R.F.-R.); (J.P.-G.)
| | | | - Gilberto González
- Department of Surgery and Bariatrics, Centro Médico Puerta de Hierro, Guadalajara 45040, Mexico;
| | | | - Raquel Franco-Rodríguez
- Department of Basic Health Science, Health Science Faculty, Rey Juan Carlos University, 28922 Madrid, Spain; (R.F.-R.); (J.P.-G.)
| | - Julio Paredes-González
- Department of Basic Health Science, Health Science Faculty, Rey Juan Carlos University, 28922 Madrid, Spain; (R.F.-R.); (J.P.-G.)
| | - Jaime Ruiz-Tovar
- Department of Health Sciences, Alfonso X El Sabio University, 28691 Madrid, Spain;
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16
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Yu C, Wang J. Quantification of the Landscape for Revealing the Underlying Mechanism of Intestinal-Type Gastric Cancer. Front Oncol 2022; 12:853768. [PMID: 35592672 PMCID: PMC9110827 DOI: 10.3389/fonc.2022.853768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 03/15/2022] [Indexed: 12/02/2022] Open
Abstract
Gastric cancer is a daunting disease with a tragic impact on global health. It is the fourth most common cancer and has become the second most frequent cause of cancer death in recent times. According to the Lauren classification, gastric cancer can be classified into two types: intestinal and diffuse. Intestinal-type gastric cancer (IGC) is more common in elderly people, and atrophic gastritis (AG) and intestinal metaplasia (IM) have been proven to be the main premalignant causes of intestinal-type gastric cancer. In turn, Helicobacter pylori infection has been identified as the most significant cause of AG and IM. In this study, we determine the mechanism of IGC progression and how H. pylori infection induces IGC. Through researching the relevant literature, we identified the key genes associated with gastric cancer and the specific genes associated with IGC. We then use hese genes to build up a gene regulatory network for IGC. Based on this gene regulatory network, we quantify the IGC landscape. Within this landscape, there are three stable states, which are classified as the normal, AG, and gastric cancer states. Through landscape topography, we can determine the biological features and progression process of IGC. To investigate the influence of H. pylori infection on IGC, we simulated different degrees of H. pylori infection. As the H. pylori infection becomes more serious, the landscape topography changes accordingly. A fourth state, named the intestinal metaplasia (IM) state, emerges on the landscape and is associated with a very high risk of developing gastric cancer. The emergence of this state is due to the interactions/regulations among genes. Through variations in the landscape topography, we can determine the influence of H. pylori infection on IGC. Finally, we use global sensitivity analysis to research the regulations most sensitive to IGC prevention or therapies. This study presents a new approach and a novel model with which to explore the mechanism of IGC. The simulations of different degrees of H. pylori infection can provide us with a systematic view of IGC progression. The key regulations found can give us some insight and guidance for clinical trials and experimental studies.
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Affiliation(s)
- Chong Yu
- Department of Statistics, Jilin University of Finance and Economics, Changchun, Jilin, China
| | - Jin Wang
- Department of Chemistry and of Physics and Astronomy, State University of New York at Stony Brook, Stony Brook, NY, United States
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17
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Vav1 Promotes B-Cell Lymphoma Development. Cells 2022; 11:cells11060949. [PMID: 35326399 PMCID: PMC8946024 DOI: 10.3390/cells11060949] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2022] [Revised: 03/06/2022] [Accepted: 03/08/2022] [Indexed: 02/07/2023] Open
Abstract
Vav1 is normally and exclusively expressed in the hematopoietic system where it functions as a specific GDP/GTP nucleotide exchange factor (GEF), firmly regulated by tyrosine phosphorylation. Mutations and overexpression of Vav1 in hematopoietic malignancies, and in human cancers of various histologic origins, are well documented. To reveal whether overexpression of Vav1 in different tissues suffices for promoting the development of malignant lesions, we expressed Vav1 in transgenic mice by using the ubiquitous ROSA26 promoter (Rosa Vav1). We detected Vav1 expression in epithelial tissues of various organs including pancreas, liver, and lung. While carcinomas did not develop in these organs, surprisingly, we noticed the development of B-cell lymphomas. Rac1-GTP levels did not change in tissues from Rosa Vav1 mice expressing the transgenic Vav1, while ERK phosphorylation increased in the lymphomas, suggesting that signaling pathways are evoked. One of the growth factors analyzed by us as a suspect candidate to mediate paracrine stimulation in the lymphocytes was CSF-1, which was highly expressed in the epithelial compartment of Rosa Vav1 mice. The expression of its specific receptor, CSF-1R, was found to be highly expressed in the B-cell lymphomas. Taken together, our results suggest a potential cross-talk between epithelial cells expressing Vav1, that secrete CSF-1, and the lymphocytes that express CSF-1R, thus leading to the generation of B-cell lymphomas. Our findings provide a novel mechanism by which Vav1 contributes to tumor propagation.
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18
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Zeng Y, Rong H, Xu J, Cao R, Li S, Gao Y, Cheng B, Zhou T. DNA Methylation: An Important Biomarker and Therapeutic Target for Gastric Cancer. Front Genet 2022; 13:823905. [PMID: 35309131 PMCID: PMC8931997 DOI: 10.3389/fgene.2022.823905] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Accepted: 02/07/2022] [Indexed: 12/12/2022] Open
Abstract
Gastric cancer (GC) is a very common malignancy with a poor prognosis, and its occurrence and development are closely related to epigenetic modifications. Methylation of DNA before or during gastric cancer is an interesting research topic. This article reviews the studies on DNA methylation related to the cause, diagnosis, treatment, and prognosis of gastric cancer and aims to find cancer biomarkers to solve major human health problems.
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Affiliation(s)
- Yunqing Zeng
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Huimin Rong
- Department of Reconstructive Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Jianwei Xu
- Department of Pancreatic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Ruyue Cao
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Shuhua Li
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Yanjing Gao
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Baoquan Cheng
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Tao Zhou
- Department of Geriatric Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- *Correspondence: Tao Zhou,
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Discovery and Validation of an Epithelial-Mesenchymal Transition-Based Signature in Gastric Cancer by Genomics and Prognosis Analysis. BIOMED RESEARCH INTERNATIONAL 2021; 2021:9026918. [PMID: 34746312 PMCID: PMC8570100 DOI: 10.1155/2021/9026918] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Accepted: 09/18/2021] [Indexed: 12/23/2022]
Abstract
Objective Epithelial-mesenchymal transition (EMT) exerts a key function in cancer initiation and progression. Herein, we aimed to develop an EMT-based prognostic signature in gastric cancer. Methods The gene expression profiles of gastric cancer were obtained from TCGA dataset as a training set and GSE66229 and GSE84437 datasets as validation sets. By LASSO regression and Cox regression analyses, key prognostic EMT-related genes were screened for developing a risk score (RS) model. Potential small molecular compounds were predicted by the CMap database based on the RS model. GSEA was employed to explore signaling pathways associated with the RS. ESTIMATE and seven algorithms (TIMER, CIBERSORT, CIBERSORT-ABS, QUANTISEQ, MCPCOUNTER, XCELL, and EPIC) were applied to assess the RS and immune microenvironment. Results This study developed an EMT-related gene signature comprised of SERPINE1, PCOLCE2, MATN3, and DKK1. High-RS patients displayed poorer survival outcomes than those with low RS. ROC curves demonstrated the robustness of the model in predicting the prognosis. After external validation, the RS model was an independent risk factor for gastric cancer. Several compounds were predicted for gastric cancer treatment based on the RS model. ECM receptor interaction, focal adhesion, pathway in cancer, TGF-beta, and WNT pathways were distinctly activated in high-RS samples. Also, high RS was significantly associated with increased stromal and immune scores and increased infiltration of CD4+ T cell, CD8+ T cell, cancer-associated fibroblast, and macrophage in gastric cancer tissues. Conclusion Our findings suggested that the EMT-related gene model may robustly predict gastric cancer prognosis, which could improve the efficacy of personalized therapy.
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20
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RNA-Seq Analysis Reveals Dendrobium officinale Polysaccharides Inhibit Precancerous Lesions of Gastric Cancer through PER3 and AQP4. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:3036504. [PMID: 34721627 PMCID: PMC8550840 DOI: 10.1155/2021/3036504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 08/23/2021] [Accepted: 09/28/2021] [Indexed: 11/18/2022]
Abstract
Purpose There has been mounting evidence that Dendrobium officinale polysaccharides (DOP), a traditional Chinese medicine, are a potential candidate treatment for N-methyl-N'-nitro-N-nitrosoguanidine- (MNNG-) induced precancerous lesions of gastric cancer (PLGC). However, the underlying mechanisms have not been adequately addressed. Method We utilized RNA-Seq analysis to investigate possible molecular targets and then used Venn software to identify the differentially expressed genes (DEGs). Further, we analyzed these DEGs with core analysis, upstream analysis, and interaction network analysis by IPA software and validated the DEGs by real-time PCR and Western blot. Result 78 DEGs were identified from the normal control group (CON), the PLGC model group (MOD), and the DOP-treated group (DOP) by the Venn software. Further analysis of these DEGs, including core analysis, upstream analysis, and interaction network analysis, was performed by Ingenuity Pathway Analysis (IPA). The main canonical pathways involved were SPINK1 Pancreatic Cancer Pathway (-log (P value) = 4.45, ratio = 0.0667) and Circadian Rhythm Signaling (-log (P value) = 2.33, ratio = 0.0606). Circadian Rhythm Signaling was strongly upregulated in the model group versus the DOP group. CLOCK was predicted to be strongly activated (z-score = 2.236) in upstream analysis and induced the downstream PER3. In addition, the relative mRNA expression levels of seven DEGs (CD2AP, ECM1, AQP4, PER3, CMTM4, ESRRG, and KCNJ15) from RT-PCR agreed with RNA-Seq data from MOD versus CON and MOD versus DOP groups. The gene and protein expression levels of PER3 and AQP4 were significantly downregulated in the PLGC model and significantly increased by DOP treatment (9.6 g/kg). Conclusions These findings not only showed DOP inhibits PLGC development by upregulating the PER3 and AQP4 gene and protein expression but also suggested that its mechanism of action involved modulating the Circadian Rhythm Signaling pathway.
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21
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Park JM, Han YM, Hahm KB. Rejuvenation of Helicobacter pylori-Associated Atrophic Gastritis Through Concerted Actions of Placenta-Derived Mesenchymal Stem Cells Prevented Gastric Cancer. Front Pharmacol 2021; 12:675443. [PMID: 34483897 PMCID: PMC8416416 DOI: 10.3389/fphar.2021.675443] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 06/22/2021] [Indexed: 01/06/2023] Open
Abstract
Chronic Helicobacter pylori infection causes gastric cancer via the progression of precancerous chronic atrophic gastritis (CAG). Therefore, repairing gastric atrophy could be a useful strategy in preventing H. pylori-associated gastric carcinogenesis. Although eradication of the bacterial pathogen offers one solution to this association, this study was designed to evaluate an alternative approach using mesenchymal stem cells to treat CAG and prevent carcinogenesis. Here, we used human placenta-derived mesenchymal stem cells (PD-MSCs) and their conditioned medium (CM) to treat H. pylori-associated CAG in a mice/cell model to explore their therapeutic effects and elucidate their molecular mechanisms. We compared the changes in the fecal microbiomes in response to PD-MSC treatments, and chronic H. pylori-infected mice were given ten treatments with PD-MSCs before being sacrificed for end point assays at around 36 weeks of age. These animals presented with significant reductions in the mean body weights of the control group, which were eradicated following PD-MSC treatment (p < 0.01). Significant changes in various pathological parameters including inflammation, gastric atrophy, erosions/ulcers, and dysplastic changes were noted in the control group (p < 0.01), but these were all significantly reduced in the PD-MSC/CM-treated groups. Lgr5+, Ki-67, H+/K+-ATPase, and Musashi-1 expressions were all significantly increased in the treated animals, while inflammatory mediators, MMP, and apoptotic executors were significantly decreased in the PD-MSC group compared to the control group (p < 0.001). Our model showed that H. pylori-initiated, high-salt diet-promoted gastric atrophic gastritis resulted in significant changes in the fecal microbiome at the phylum/genus level and that PD-MSC/CM interventions facilitated a return to more normal microbial communities. In conclusion, administration of PD-MSCs or their conditioned medium may present a novel rejuvenating agent in preventing the progression of H. pylori-associated premalignant lesions.
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Affiliation(s)
- Jong Min Park
- College of Oriental Medicine, Daejeon University, Daejeon, Korea
| | - Young Min Han
- Western Seoul Center, Korea Basic Science Institute, Seoul, Korea
| | - Ki Baik Hahm
- Medpacto Research Institute, Medpacto, Seoul, Korea.,CHA Cancer Preventive Research Center, CHA Bio Complex, Seongnam, Korea
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22
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Kim HJ, Kim N, Park JH, Choi S, Shin CM, Lee OJ. Helicobacter pylori Eradication Induced Constant Decrease in Interleukin- 1B Expression over More Than 5 Years in Patients with Gastric Cancer and Dysplasia. Gut Liver 2021; 14:735-745. [PMID: 32703913 PMCID: PMC7667922 DOI: 10.5009/gnl19312] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Revised: 11/16/2019] [Accepted: 11/17/2019] [Indexed: 12/11/2022] Open
Abstract
Background/Aims Helicobacter pylori (Hp) suppresses gastric acid secretion by repressing the expression of the H+, K+-adenosine triphosphatase (H+, K+-ATPase) and stimulating interleukin-1 (IL-1β; encoded by IL-1B). This study was aimed at evaluating the expression of the H+, K+-ATPase and IL-1β after Hp eradication. Methods Two hundred twenty-one subjects were categorized as Hp-negative (n=84) or Hp-positive (n=137) according to the results of Hp tests (histology, CLO test, culturing, and serology). The mRNA expression levels of IL-1B and ATP4A (the gene encoding the α-subunit of H+, K+-ATPase) were measured in biopsy specimens from the gastric corpus using real-time polymerase chain reaction. Results The Hp-positive group had significantly higher IL-1B mRNA levels than the whole Hp-negative group and the intestinal metaplasia (IM)-negative subgroup. After Hp eradication, the difference between the Hp-negative and Hp-eradicated groups disappeared, including in the IM-negative subgroup. The IL-1B mRNA level did not significantly change from the baseline level. Within the gastric cancer (GC)/dysplasia subgroup, the IL-1B mRNA levels at 1, 2, 3–4, and ≥5 years after Hp eradication were significantly lower than the baseline level. The difference in ATP4A mRNA levels between the Hp-negative and Hp-positive groups was not significant at baseline, and the changes in the ATP4A mRNA levels after Hp eradication compared to the baseline levels in the whole group and subgroups stratified by the presence of IM and GC/dysplasia were not significant. Conclusions Infection with Hp has an effect on the level of IL-1B mRNA in IM-negative subjects. The continuous reduction in the IL-1B mRNA level in patients with GC/dysplasia after Hp eradication contributes to the prevention of metachronous GC after Hp eradication.
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Affiliation(s)
- Hee Jin Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine, Gyeongsang National University College of Medicine and Gyeongsang National University Changwon Hospital, Changwon, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University, Seoul, Korea
| | - Ji Hyun Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University, Seoul, Korea
| | - Sunkyu Choi
- Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University, Seoul, Korea
| | - Ok Jae Lee
- Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University College of Medicine and Gyeongsang National University Hospital, Jinju, Korea
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23
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Park Y, Ki M. Population Attributable Fraction of Helicobacter pylori Infection-Related Gastric Cancer in Korea: A Meta-Analysis. Cancer Res Treat 2021; 53:744-753. [PMID: 33321562 PMCID: PMC8291171 DOI: 10.4143/crt.2020.610] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 12/14/2020] [Indexed: 12/11/2022] Open
Abstract
PURPOSE This study aimed to determine the proportion of gastric cancer attributable to Helicobactor pylori in the Korean population. Infection with H. pylori has been recognized as the most significant risk factor for gastric cancer. In Korea, gastric cancer is the most common cancer that accounted for 13.3% of all cancers in 2016. In particular, men are most commonly diagnosed with gastric cancer; the age-standardized incidence rate in men is 49.6 per 100,000, which is more than twice the incidence in women. MATERIALS AND METHODS The population attributable fraction (PAF) was calculated as a function of the relative risk (RR) of gastric cancer associated with H. pylori infections. To estimate PAF of gastric cancer due to H. pylori, the prevalence of H. pylori infections was extrapolated for the year of 1990 and a pooled RR was obtained by conducting a meta-analysis of studies recently published in Korea. RESULTS The estimated prevalence of H. pylori was 76.4% in men and 71.9% in women. The RRs (95% confidence interval) pooled from case-control studies using a random effects model was 1.69 (1.29-2.22) for overall gastric cancer and 2.17 (1.04-4.55) for non-cardia gastric cancer. Using the RR for overall gastric cancer, the estimated PAFs due to H. pylori were 34.5% in men and 33.2% in women. CONCLUSION The occurrence of gastric cancer in Koreans may be affected by other risk factors in addition to H. pylori infection, which may contribute to increasing baseline risk for gastric cancer.
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Affiliation(s)
- Yoon Park
- Department of Cancer Control and Population Health, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea
| | - Moran Ki
- Department of Cancer Control and Population Health, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea
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24
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Watari J, Tomita T, Tozawa K, Oshima T, Fukui H, Miwa H. Preventing Metachronous Gastric Cancer after the Endoscopic Resection of Gastric Epithelial Neoplasia: Roles of Helicobacter pylori Eradication and Aspirin. Gut Liver 2021; 14:281-290. [PMID: 31547640 PMCID: PMC7234884 DOI: 10.5009/gnl19079] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Revised: 05/11/2019] [Accepted: 06/06/2019] [Indexed: 12/13/2022] Open
Abstract
Whether Helicobacter pylori eradication actually reduces the risk of metachronous gastric cancer (MGC) development remains a controversial question. In this review, we addressed this topic by reviewing the results of clinical investigations and molecular pathological analyses of the roles of H. pylori eradication and aspirin administration in the prevention of MGC. In regard to the clinical studies, the results of meta-analyses and randomized control trials differ from those of retrospective studies: the former trials show that H. pylori eradication has a preventive effect on MGC, while the latter studies do not. This discrepancy may be at least partly attributable to differences in the follow-up periods: H. pylori eradication is more likely to prevent MGC over a long-term follow-up period (≥5 years) than over a short-term follow-up period. In addition, many studies have shown that aspirin may have an additive effect on MGC-risk reduction after H. pylori eradication has been achieved. Both H. pylori eradication and aspirin use induce molecular alterations in the atrophic gastritis mucosa but not in the intestinal metaplasia. Unfortunately, the molecular pathological analyses of these interventions have been limited by short follow-up periods. Therefore, a long-term prospective cohort is needed to clarify the changes in molecular events caused by these interventions.
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Affiliation(s)
- Jiro Watari
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Toshihiko Tomita
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Katsuyuki Tozawa
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Tadayuki Oshima
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Hirokazu Fukui
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Hiroto Miwa
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
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25
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Lu W, Ni Z, Jiang S, Tong M, Zhang J, Zhao J, Feng C, Jia Q, Wang J, Yao T, Ning H, Shi Y. Resveratrol inhibits bile acid-induced gastric intestinal metaplasia via the PI3K/AKT/p-FoxO4 signalling pathway. Phytother Res 2021; 35:1495-1507. [PMID: 33103284 PMCID: PMC8048559 DOI: 10.1002/ptr.6915] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Revised: 10/05/2020] [Accepted: 10/05/2020] [Indexed: 02/06/2023]
Abstract
Gastric intestinal metaplasia (GIM) is the essential pre-malignancy of gastric cancer. Chronic inflammation and bile acid reflux are major contributing factors. As an intestinal development transcription factor, caudal-related homeobox 2 (CDX2) is key in GIM. Resveratrol has potential chemopreventive and anti-tumour effects. The aim of the study is to probe the effect of resveratrol in bile acid-induced GIM. We demonstrated that resveratrol could reduce CDX2 expression in a time- and dose-dependent manner in gastric cell lines. A Cignal Finder 45-Pathway Reporter Array and TranSignal Protein/DNA Array Kit verified that resveratrol could increase Forkhead box O4 (FoxO4) activity and that Chenodeoxycholic acid (CDCA) could reduce FoxO4 activity. Furthermore, bioinformatics analysis showed that FoxO4 could bind to the CDX2 promoter, and these conjectures were supported by chromatin-immunoprecipitation (ChIP) assays. Resveratrol can activate FoxO4 and decrease CDX2 expression by increasing phospho-FoxO4 nucleus trans-location. Resveratrol could increase FoxO4 phosphorylation through the PI3K/AKT pathway. Ectopic FoxO4 expression can up-regulate FoxO4 phosphorylation and suppress CDCA-induced GIM marker expression. Finally, we found a reverse correlation between p-FoxO4 and CDX2 in tissue arrays. This study validates that resveratrol could reduce bile acid-induced GIM through the PI3K/AKT/p-FoxO4 signalling pathway and has a potential reversing effect on GIM, especially that caused by bile acid reflux.
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Affiliation(s)
- Wenquan Lu
- Department of GastroenterologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesAir force Military Medical UniversityXi'anChina
| | - Zhen Ni
- Department of GastroenterologyThe General Hospital of Western Theater CommandChengduChina
| | - Shuqin Jiang
- Pediatric Development and Behavior DepartmentThe third Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
| | - Mingfu Tong
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesAir force Military Medical UniversityXi'anChina
- Department of GastroenterologyBeijing Chao‐Yang Hospital, Capital Medical UniversityBeijingChina
| | - Jian Zhang
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesAir force Military Medical UniversityXi'anChina
| | - Jing Zhao
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesAir force Military Medical UniversityXi'anChina
- Department of GastroenterologySecond Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Chenchen Feng
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesAir force Military Medical UniversityXi'anChina
- Postgraduate DepartmentXi'an Medical UniversityXi'anChina
| | - Qiaoyu Jia
- Department of GastroenterologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
| | - Jingyun Wang
- Department of GastroenterologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
| | - Tingting Yao
- Department of GastroenterologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
| | - Hanbing Ning
- Department of GastroenterologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
| | - Yongquan Shi
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesAir force Military Medical UniversityXi'anChina
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26
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Gravina AG, Priadko K, Ciamarra P, Granata L, Facchiano A, Miranda A, Dallio M, Federico A, Romano M. Extra-Gastric Manifestations of Helicobacter pylori Infection. J Clin Med 2020; 9:3887. [PMID: 33265933 PMCID: PMC7761397 DOI: 10.3390/jcm9123887] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 11/21/2020] [Accepted: 11/26/2020] [Indexed: 12/13/2022] Open
Abstract
Helicobacter Pylori (H. pylori) is a Gram-negative flagellated microorganism that has been extensively studied since its first isolation due to its widespread diffusion and association with numerous diseases. While the bacterium is proved to be a causative factor for a number of gastric diseases such as gastritis, gastric adenocarcinoma, and MALT-lymphoma, its role at other gastrointestinal levels and in other systems is being thoroughly studied. In this article, we reviewed the latest published clinical and laboratory studies that investigated associations of H. pylori with hematologic diseases such as Vitamin B12- and iron-deficiency anemia, primary immune thrombocytopenia, and with a number of dermatologic and ophthalmic diseases. In addition, the putative role of the bacterium in inflammatory bowel diseases, esophageal disorders, metabolic, diseases, neurologic diseases and allergy were outlined.
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Affiliation(s)
- Antonietta G. Gravina
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, via Pansini 5, 80131 Naples, Italy; (K.P.); (P.C.); (L.G.); (A.F.); (A.M.); (M.D.); (A.F.)
| | | | | | | | | | | | | | | | - Marco Romano
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, via Pansini 5, 80131 Naples, Italy; (K.P.); (P.C.); (L.G.); (A.F.); (A.M.); (M.D.); (A.F.)
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27
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Feng X, Han L, Ma S, Zhao L, Wang L, Zhang K, Yin P, Guo L, Jing W, Li Q. Microbes in Tumoral In Situ Tissues and in Tumorigenesis. Front Cell Infect Microbiol 2020; 10:572570. [PMID: 33330121 PMCID: PMC7732458 DOI: 10.3389/fcimb.2020.572570] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 10/23/2020] [Indexed: 12/14/2022] Open
Abstract
Cancerous tumors are severe diseases affecting human health that have a complicated etiology and pathogenesis. Microbes have been considered to be related to the development and progression of numerous tumors through various pathogenic mechanisms in recent studies. Bacteria, which have so far remained the most studied microbes worldwide, have four major possible special pathogenic mechanisms (modulation of inflammation, immunity, DNA damage, and metabolism) that are related to carcinogenesis. This review aims to macroscopically summarize and verify the relationships between microbes and tumoral in situ tissues from cancers of four major different systems (urinary, respiratory, digestive, and reproductive); the abovementioned four microbial pathogenic mechanisms, as well as some synergistic pathogenic mechanisms, are also discussed. Once the etiologic role of microbes and their precise pathogenic mechanisms in carcinogenesis are known, the early prevention, diagnosis, and treatment of cancers would progress significantly.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Qiling Li
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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28
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Toyoshima O, Nishizawa T, Sakitani K, Yamakawa T, Takahashi Y, Kinoshita K, Torii A, Yamada A, Suzuki H, Koike K. Helicobacter pylori eradication improved the Kyoto classification score on endoscopy. JGH Open 2020; 4:909-914. [PMID: 33102763 PMCID: PMC7578336 DOI: 10.1002/jgh3.12360] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Revised: 03/31/2020] [Accepted: 05/07/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Endoscopy-based Kyoto classification predicts the risk of Helicobacter pylori infection and gastric cancer; however, the change in score following H. pylori eradication remains unknown. We retrospectively compared the Kyoto score before and after H. pylori eradication. METHODS H. pylori-positive patients who underwent baseline esophagogastroduodenoscopy (EGD), successful H. pylori eradication, and surveillance EGD were enrolled. The Kyoto score is a sum of scores for atrophy (Kimura-Takemoto atrophic-border classification none or C1: 0, C-II or C-III: 1, O-I to O-III: 2), intestinal metaplasia (none: 0, antrum: 1, corpus and antrum: 2), enlarged folds (absence: 0, presence: 1), nodularity (absence: 0, presence: 1), and diffuse redness (none: 0, mild: 1, severe: 2) and ranges from 0 to 8. RESULTS Eighty-three patients (mean age: 54.9 years; 65.1% women) were enrolled. The mean duration from successful eradication to surveillance EGD was 256 days. The Kyoto score significantly decreased from 3.90 to 2.78 following H. pylori eradication (P < 0.001). Scores for endoscopic atrophy (from 1.43 to 1.46, P = 0.638) and endoscopic intestinal metaplasia (from 0.53 to 0.47, P = 0.543) did not change; however, there was significant improvement in the scores for enlarged folds (from 0.14 to 0.00, P = 0.002), nodularity (from 0.18 to 0.04, P = 0.002), and diffuse redness (from 1.61 to 0.82, P < 0.001). CONCLUSION The Kyoto classification score decreased following H. pylori eradication. A decrease in the scores for enlarged folds, nodularity, and diffuse redness contributed to the decrease in Kyoto score.
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Affiliation(s)
- Osamu Toyoshima
- Department of GastroenterologyToyoshima Endoscopy ClinicTokyoJapan
- Department of Gastroenterology, Graduate School of MedicineThe University of TokyoTokyoJapan
| | - Toshihiro Nishizawa
- Department of GastroenterologyToyoshima Endoscopy ClinicTokyoJapan
- Department of Gastroenterology and HepatologyInternational University of Health and Welfare, Mita HospitalTokyoJapan
| | - Kosuke Sakitani
- Department of GastroenterologyToyoshima Endoscopy ClinicTokyoJapan
- Department of GastroenterologySakitani Endoscopy ClinicChibaJapan
| | | | - Yoshiyuki Takahashi
- Department of GastroenterologyToyoshima Endoscopy ClinicTokyoJapan
- Department of GastroenterologyHigashi‐Koganei Sakura ClinicTokyoJapan
| | - Kazunori Kinoshita
- Department of Obstetrics and GynecologySeijo Kinoshita HospitalTokyoJapan
| | - Akira Torii
- Department of GastroenterologyTorii Naika ClinicTokyoJapan
| | - Atsuo Yamada
- Department of Gastroenterology, Graduate School of MedicineThe University of TokyoTokyoJapan
| | - Hidekazu Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of MedicineTokai UniversityTokyoJapan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of MedicineThe University of TokyoTokyoJapan
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29
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Kim N. Reversal of the Methylation-Associated Regulation of miR-200a/b by Helicobacter pylori Eradication Contributes to the Chemoprevention of Gastric Carcinogenesis. Gut Liver 2020; 14:533-534. [PMID: 32921637 PMCID: PMC7492488 DOI: 10.5009/gnl20251] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Affiliation(s)
- Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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30
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Noh G, Kim N, Choi Y, Lee HS, Hwang YJ, Kim HJ, Yoon H, Shin CM, Park YS, Lee DH. Long-term follow up of serum pepsinogens in patients with gastric cancer or dysplasia after Helicobacter pylori eradication. J Gastroenterol Hepatol 2020; 35:1540-1548. [PMID: 32090375 DOI: 10.1111/jgh.15017] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 01/12/2020] [Accepted: 02/21/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM Few studies have evaluated the change in serum pepsinogen (sPG) levels after the eradication of Helicobacter pylori. The aim of this study was to evaluate the effect of H. pylori eradication on sPG levels in patients with gastric cancer/dysplasia in comparison to a control group. METHODS We prospectively enrolled 368 patients with gastric cancer/dysplasia and 610 control subjects. H. pylori status and sPG levels were measured before and after eradication. The follow-up time points were classified as < 12, 12-23, 24-35, and ≥ 36 months. RESULTS In 179 H. pylori-eradicated patients with gastric cancer/dysplasia and 168 control group subjects, sPG I significantly decreased, and the sPG I/II ratio significantly increased after eradication compared to baseline, and this improvement in sPG values was maintained during all follow-up time points. Significant differences in sPG I and the sPG I/II ratio were observed between the gastric cancer/dysplasia group and the control group < 24 months after eradication. However, these differences in sPG values disappeared after ≥ 24 months of follow up. Moreover, significant differences in the intestinal metaplasia grade were observed between these two groups before eradication until < 24 months after eradication. However, these differences in the intestinal metaplasia grade disappeared after ≥ 24 months of follow up in the corpus. CONCLUSION The sPG values and intestinal metaplasia grade (corpus) in the gastric cancer/dysplasia group became similar to those in the control group at long-term follow up after H. pylori eradication. It might be related with the reduction of metachronous gastric neoplasm.
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Affiliation(s)
- Gitark Noh
- Departments of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Nayoung Kim
- Departments of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University, Seoul, South Korea.,Tumor Microenvironment Global Core Research Center, Seoul National University, Seoul, South Korea
| | - Yonghoon Choi
- Departments of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Hye Seung Lee
- Departments of Pathology, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Young Jae Hwang
- Departments of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Hee Jin Kim
- Department of Internal Medicine, Myongji Hospital, Goyang, South Korea
| | - Hyuk Yoon
- Departments of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Cheol Min Shin
- Departments of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Young Soo Park
- Departments of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Dong Ho Lee
- Departments of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University, Seoul, South Korea.,Tumor Microenvironment Global Core Research Center, Seoul National University, Seoul, South Korea
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31
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Baj J, Korona-Głowniak I, Forma A, Maani A, Sitarz E, Rahnama-Hezavah M, Radzikowska E, Portincasa P. Mechanisms of the Epithelial-Mesenchymal Transition and Tumor Microenvironment in Helicobacter pylori-Induced Gastric Cancer. Cells 2020; 9:1055. [PMID: 32340207 PMCID: PMC7225971 DOI: 10.3390/cells9041055] [Citation(s) in RCA: 105] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 04/16/2020] [Accepted: 04/17/2020] [Indexed: 12/11/2022] Open
Abstract
Helicobacter pylori (H. pylori) is one of the most common human pathogens, affecting half of the world's population. Approximately 20% of the infected patients develop gastric ulcers or neoplastic changes in the gastric stroma. An infection also leads to the progression of epithelial-mesenchymal transition within gastric tissue, increasing the probability of gastric cancer development. This paper aims to review the role of H. pylori and its virulence factors in epithelial-mesenchymal transition associated with malignant transformation within the gastric stroma. The reviewed factors included: CagA (cytotoxin-associated gene A) along with induction of cancer stem-cell properties and interaction with YAP (Yes-associated protein pathway), tumor necrosis factor α-inducing protein, Lpp20 lipoprotein, Afadin protein, penicillin-binding protein 1A, microRNA-29a-3p, programmed cell death protein 4, lysosomal-associated protein transmembrane 4β, cancer-associated fibroblasts, heparin-binding epidermal growth factor (HB-EGF), matrix metalloproteinase-7 (MMP-7), and cancer stem cells (CSCs). The review summarizes the most recent findings, providing insight into potential molecular targets and new treatment strategies for gastric cancer.
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Affiliation(s)
- Jacek Baj
- Chair and Department of Anatomy, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Izabela Korona-Głowniak
- Department of Pharmaceutical Microbiology with Laboratory for Microbiological Diagnostics, Medical University of Lublin, Chodzki 1 Street, 20-093 Lublin, Poland;
| | - Alicja Forma
- Chair and Department of Forensic Medicine, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Amr Maani
- Chair and Department of Anatomy, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Elżbieta Sitarz
- Chair and 1st Department of Psychiatry, Psychotherapy and Early Intervention, Medical University of Lublin, Gluska Street 1, 20-439 Lublin, Poland;
| | - Mansur Rahnama-Hezavah
- Chair and Department of Oral Surgery, Medical University of Lublin, 20-081 Lublin, Poland;
| | - Elżbieta Radzikowska
- Department of Plastic Surgery, Central Clinical Hospital of the MSWiA in Warsaw, 01-211 Warsaw, Poland;
| | - Piero Portincasa
- Clinica Medica A. Murri, Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro Medical School, 70126 Bari, Italy;
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32
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Lv X, Zhao Y, Zhang L, Zhou S, Zhang B, Zhang Q, Jiang L, Li X, Wu H, Zhao L, Wei M, He M. Development of a novel gene signature in patients without Helicobacter pylori infection gastric cancer. J Cell Biochem 2019; 121:1842-1854. [PMID: 31633246 DOI: 10.1002/jcb.29419] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2019] [Accepted: 10/08/2019] [Indexed: 02/06/2023]
Abstract
Gastric cancer (GC) is one of the most fatal common cancers in worldwide. Helicobacter pylori (H. pylori) infection is closely related to the development of GC, although the mechanism is still unclear. In our study, we aim to develop a robust messenger RNA (mRNA) signature associated with H. pylori (-) GC that can sensitively and efficiently predict the prognostic. The RNA-seq expression profile and corresponding clinical data of 598 gastric cancer samples and 63 normal samples obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database. Using gene set enrichment analysis H. pylori (+) GC and H. pylori (-) GC patients and normal samples to select certain genes for further analysis. Using univariate and multivariate Cox regression model to establish a gene signature for predicting the overall survival (OS). Finally, we identified G2/M related seven-mRNA signature (TGFB1, EGF, MKI67, ILF3, INCENP, TNPO2, and CHAF1A) closely related to the prognosis of patients with H. pylori (-) GC. The seven-mRNA signature was identified to act as an independent prognostic biomarker by stratified analysis and multivariate Cox regression analysis. It was also validated on two test groups from TCGA and GSE15460 and shown that patients with high-risk scores based on the expression of the seven mRNAs had significantly shorter survival times compared to patients with low-risk scores (P < .0001). In this study, we developed a seven-mRNA signature related to G2/M checkpoint from H. pylori (-) GCs that as an independent biomarker potentially with a good performance in predicting OS and might be valuable for the clinical management for patients with GC.
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Affiliation(s)
- Xuemei Lv
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
| | - Yanyun Zhao
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
| | - Liwen Zhang
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
| | - Shuqi Zhou
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
| | - Bing Zhang
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
| | - Qiang Zhang
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
| | - Longyang Jiang
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
| | - Xueping Li
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
| | - Huizhe Wu
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
| | - Lin Zhao
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
| | - Minjie Wei
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
| | - Miao He
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.,Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, Liaoning, China
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33
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Li L, Yu C. Helicobacter pylori Infection following Endoscopic Resection of Early Gastric Cancer. BIOMED RESEARCH INTERNATIONAL 2019; 2019:9824964. [PMID: 31737682 PMCID: PMC6816031 DOI: 10.1155/2019/9824964] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Revised: 07/29/2019] [Accepted: 08/20/2019] [Indexed: 12/14/2022]
Abstract
The role of Helicobacter pylori (H. pylori) infection in patients following endoscopic resection of early gastric cancer (EGC) remains unclear. This article presents a review of literature published in the past 15 years. H. pylori-mediated persistent methylation levels are associated with the development of metachronous gastric cancer. The methylation of certain specific genes can be used to identify patients with a high risk of metachronous gastric cancer even after H. pylori eradication. H. pylori eradication after endoscopic resection should be performed as early as possible for eradication success and prevention of metachronous precancerous lesions. Although whether the eradication of H. pylori could prevent the development of metachronous cancer after endoscopic resection is controversial, several meta-analyses concluded that H. pylori eradication could reduce the incidence of metachronous gastric cancer significantly. In addition, H. pylori eradication in gastric cancer survivors after endoscopic resection could reduce healthcare cost and save lives in a cost-effective way. Taken together, H. pylori eradication after endoscopic resection of EGC is recommended as prevention for metachronous precancerous lesions and metachronous gastric cancer.
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Affiliation(s)
- Lan Li
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Chaohui Yu
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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34
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Kountouras J, Doulberis M, Papaefthymiou A, Polyzos SA, Touloumtzi M, Elisabeth V, Kapetanakis N, Liatsos C, Gavalas E, Katsinelos P. Helicobacter pylori infection and gastrointestinal tract cancer biology: considering a double-edged sword reflection. Cell Mol Life Sci 2019; 76:2487-2488. [PMID: 31006036 PMCID: PMC11105426 DOI: 10.1007/s00018-019-03106-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Revised: 04/10/2019] [Accepted: 04/12/2019] [Indexed: 02/08/2023]
Affiliation(s)
- Jannis Kountouras
- Department of Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, 8 Fanariou St, Byzantio, 551 33, Thessaloniki, Macedonia, Greece.
| | - Michael Doulberis
- Department of Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, 8 Fanariou St, Byzantio, 551 33, Thessaloniki, Macedonia, Greece
- Department of Gastroenterology and Hepatology, University of Zurich, 8091, Zurich, Switzerland
| | - Apostolis Papaefthymiou
- Department of Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, 8 Fanariou St, Byzantio, 551 33, Thessaloniki, Macedonia, Greece
| | - Stergios A Polyzos
- First Department of Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, 54642, Thessaloniki, Macedonia, Greece
| | - Maria Touloumtzi
- Department of Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, 8 Fanariou St, Byzantio, 551 33, Thessaloniki, Macedonia, Greece
| | - Vardaka Elisabeth
- Department of Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, 8 Fanariou St, Byzantio, 551 33, Thessaloniki, Macedonia, Greece
| | - Nikolaos Kapetanakis
- Department of Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, 8 Fanariou St, Byzantio, 551 33, Thessaloniki, Macedonia, Greece
| | - Christos Liatsos
- Department of Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, 8 Fanariou St, Byzantio, 551 33, Thessaloniki, Macedonia, Greece
| | - Emmanouel Gavalas
- Department of Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, 8 Fanariou St, Byzantio, 551 33, Thessaloniki, Macedonia, Greece
| | - Panagiotis Katsinelos
- Department of Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, 8 Fanariou St, Byzantio, 551 33, Thessaloniki, Macedonia, Greece
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