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Zeng L, Li H, Huang T, Heng Y, Liu J, Hu X. The simplified depth-predicting score outperforms the depth-predicting score for predicting the depth of invasion in differentiated early gastric cancer patients among nonexpert endoscopists. GASTROENTEROLOGIA Y HEPATOLOGIA 2025; 48:502265. [PMID: 39395693 DOI: 10.1016/j.gastrohep.2024.502265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 08/25/2024] [Accepted: 10/06/2024] [Indexed: 10/14/2024]
Abstract
AIM Endoscopists utilize depth-predicting score (DPS) and simplified depth-predicting score (S-DPS) to predict the invasion depth of early gastric cancer based on conventional white-light endoscopic features. The effectiveness of these scores has not been fully elucidated among nonexpert endoscopists. This study aimed to compare the ability of DPS and S-DPS to predict invasion depth of differentiated early gastric cancers by nonexpert endoscopists. PARTICIPANTS AND METHODS We collected subitem scores of DPS and S-DPS from 19 nonexpert endoscopists for early gastric cancer conventional white-light endoscopy images in the test dataset to predict the invasion depth of the early gastric cancer conventional white-light endoscopy images. Accuracy, specificity, overdiagnosis rate, and underdiagnosis rate were subsequently calculated using the histological invasion depth as the gold standard. RESULTS Using 3 as the cutoff line, the overall S-DPS diagnostic accuracy for invasion depth was significantly greater than that of DPS [73.86% (69.32%, 75.00%) vs. 67.05% (62.50%, 71.59%), p=0.005]. The overall S-DPS overdiagnosis rate was significantly lower than that of DPS [7.58% (3.03%, 13.64%) vs. 28.79% (18.18%, 37.88%), p=0.000]. The overall S-DPS under-diagnosed rate was significantly higher than that of DPS [86.36% (68.18%, 90.91%) vs. 45.45% (31.82%, 59.09%), p=0.000]. The specificity of the S-DPS was significantly greater than that of DPS [92.42% (86.36%, 96.97%) vs. 71.21% (62.12%, 81.82%), p=0.000]. CONCLUSION The diagnostic accuracy of the S-DPS was greater than that of the DPS among nonexpert endoscopists. Furthermore, S-DPS is simpler than other methods, making it more conducive to clinical application for nonexpert endoscopists.
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Affiliation(s)
- Lulu Zeng
- Department of Gastroenterology, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
| | - Hui Li
- Department of Gastroenterology, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
| | - Tian Huang
- Department of Gastroenterology, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
| | - Yuting Heng
- Department of Gastroenterology, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
| | - Jun Liu
- Department of Pathophysiology, School of Basic Medical College, Anhui Medical University, Hefei, Anhui Province, China; Functional Experiment Center, School of Basic Medical College, Anhui Medical University, Hefei, Anhui Province, China.
| | - Xiangpeng Hu
- Department of Gastroenterology, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China.
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Zhang F, Zhou C, Wang X, Liu Y, Hou Y, Niu L. INHBA, transcriptionally activated by SPI1, facilitates gastric cancer progression by inducing macrophage recruitment and M2 polarization via activating the TGF-β signaling to increase CCL2. Pathol Res Pract 2025; 269:155920. [PMID: 40132395 DOI: 10.1016/j.prp.2025.155920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Revised: 03/15/2025] [Accepted: 03/17/2025] [Indexed: 03/27/2025]
Abstract
Tumor-associated macrophages (TAMs) are associated with the occurrence, development, and poor prognosis of human cancers. Inhibin beta A subunit (INHBA) is found to be aberrantly upregulated in gastric cancer (GC). However, whether INHBA is involved in macrophage recruitment and M2 polarization is unclear. Herein, INHBA expression was increased in GC tumor tissues and cells. INHBA expression was positively correlated with macrophage infiltration and M2 macrophage markers. Knockdown of INHBA in GC cells suppressed macrophage recruitment and M2 polarization by downregulaitng CCL2 expression and secretion. Mechanistic assays showed that SPI1 could bind to INHBA and transcriptionally activate its expression. SPI1 promoted macrophage recruitment and M2 polarization by upregulating INHBA expression. Moreover, SPI1 induced CCL2 expression by regulating INHBA in GC cells. INHBA upregulated CCL2 expression by activating the TGF-β signaling. Furthermore, SPI1-induced macrophages facilitated cell proliferation, migration, and invasion by increasing INHBA expression. INHBA-induced macrophages promoted cell proliferation, migration, and invasion by inducing CCL2 expression. Additionally, knockdown of INHBA inhibited tumor growth in vivo. In conclusion, SPI1 induces the macrophage recruitment and M2 polarization by transcriptionally regulating INHBA to activating the TGF-β signaling, thereby upregulating CCL2 expression and then contributing to GC cell malignant progression. Targeting SPI1/INHBA/CCL2 axis might be a promising therapeutic strategy for GC and potentially used for cancer immunotherapy.
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Affiliation(s)
- Fan Zhang
- Department of Medical Oncology, Shaanxi Provincial People's Hospital, Xi'an 710068, China
| | - Congya Zhou
- Department of Radiotherapy, Shaanxi Provincial People's Hospital, Xi'an 710068, China
| | - Xifang Wang
- Department of Medical Oncology, Shaanxi Provincial People's Hospital, Xi'an 710068, China
| | - Ying Liu
- Department of Medical Oncology, Shaanxi Provincial People's Hospital, Xi'an 710068, China
| | - Yinyin Hou
- Department of Medical Oncology, Shaanxi Provincial People's Hospital, Xi'an 710068, China
| | - Lu Niu
- Department of Gastroenterology, Shaanxi Provincial People's Hospital, Xi'an 710068, China.
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Carneiro KDO, Araújo TMT, Da Silva Mourão RM, Casseb SMM, Demachki S, Moreira FC, Dos Santos ÂKCR, Ishak G, Da Costa DDSA, Magalhães L, Vidal AF, Burbano RMR, de Assumpção PP. Transcriptional and microbial profile of gastric cancer patients infected with Epstein-Barr virus. Front Oncol 2025; 15:1530430. [PMID: 40110195 PMCID: PMC11919665 DOI: 10.3389/fonc.2025.1530430] [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: 11/18/2024] [Accepted: 02/17/2025] [Indexed: 03/22/2025] Open
Abstract
Introduction Gastric cancer (GC), which has low survival rates and high mortality, is a major concern, particularly in Asia and South America, with over one million annual cases. Epstein-Barr virus (EBV) is recognized as a carcinogen that may trigger gastric carcinogenesis by infecting the stomach epithelium via reactivated B cells, with growing evidence linking it to GC. This study investigates the transcriptional and microbial profiles of EBV-infected versus EBV-non-infected GC patients. Methods Using Illumina NextSeq, cDNA libraries were sequenced, and reads were aligned to the human genome and analyzed with DESeq2. Kegg and differential analyses revealed key genes and pathways. Gene sensitivity and specificity were assessed using ROC curves (p < 0.05, AUC > 0.8). Non-aligned reads were used for microbiome analysis with Kraken2 for bacterial identification. Microbial analysis included LDA score, Alpha and Beta diversity metrics, with significance set at p ≤ 0.05. Spearman's correlation between differentially expressed genes (DEGs) and bacteria were also examined. Results The data revealed a gene expression pattern in EBV-positive gastric cancer, highlighting immune response, inflammation, and cell proliferation genes (e.g., GBP4, ICAM1, IL32, TNFSF10). ROC analysis identified genes with high specificity and sensitivity for discriminating EBV+ gastric cancer, including GBP5, CMKLR1, GM2A and CXCL11 that play pivotal roles in immune response, inflammation, and cancer. Functional enrichment pointed to cytokine-cytokine receptor interactions, antigen processing, and Th17 immune response, emphasizing the role of the tumor microenvironment, shaped by inflammation and immunomodulation, in EBV-associated GC. Microbial analysis revealed changes in the gastric microbiota in EBV+ samples, with a significant reduction in bacterial taxa. The genera Choristoneura and Bartonella were more abundant in EBV+ GC, while more abundant bacteria in EBV- GC included Citrobacter, Acidithiobacillus and Biochmannia. Spearman's correlation showed a strong link between DE bacterial genera and DEGs involved in processes like cell differentiation, cytokine production, digestion, and cell death. Conclusion These findings suggest a complex interaction between the host (EBV+ GC) and the microbiota, possibly influencing cancer progression, and offering potential therapeutic targets such as microbiota modulation or gene regulation. Comparing with EBV- samples further highlights the specific impact of EBV and the microbiota on gastric cancer pathogenesis.
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Affiliation(s)
| | | | | | | | - Samia Demachki
- Oncology Research Center, Federal University of Pará, Belém, Brazil
| | | | | | - Geraldo Ishak
- Oncology Research Center, Federal University of Pará, Belém, Brazil
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Modesto VC, Galvão ND, Souza RAGD, Alves MR, Bustamante-Teixeira MT, Andrade ACDS. Time trends in the incidence of cancer in the state of Mato Grosso, Brazil, from 2001 to 2016. CIENCIA & SAUDE COLETIVA 2025; 30:e05932023. [PMID: 40136161 DOI: 10.1590/1413-81232025303.05932023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Accepted: 12/14/2023] [Indexed: 03/27/2025] Open
Abstract
The scope was to analyze the time-series trend in the incidence of cancer in the health macro-regions of the State of Mato Grosso from 2001 to 2016. It involved an ecological time-series study with data from the Mato Grosso Population-Based Cancer Registry. Age-standardized incidence rates, disaggregated by year, sex, macro-region and type of cancer, were calculated. For men, the trend was increasing for prostate cancer in the state and the Central-Northwest, East, West, and South macro-regions, and for colorectal cancer in the North; and decreasing for stomach cancer in the state and the Central-Northwest and North, for lung cancer in the East, and for esophageal cancer in the Central-Northwest. For women, the trend was increasing for breast cancer in the state from 2009 to 2016, for lung cancer in the state (2008 to 2016) and in the Central-North (2001 to 2016) and South (2007 to 2016) macro-regions; and decreasing for cervical cancer in the state and for all macro-regions, and for stomach cancer in the state and in the Central-Northwest. Colorectal cancer revealed a stable trend for the state and all macro-regions. Cancer surveillance, prevention and control actions should consider regional differences and variations in magnitude of the occurrence of the disease.
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Affiliation(s)
- Viviane Cardozo Modesto
- Programa de Pós-Graduação em Saúde Coletiva, Universidade Federal de Mato Grosso. Av. Fernando Correa da Costa 2367. 78060-900 Cuiabá MT Brasil.
| | - Noemi Dreyer Galvão
- Programa de Pós-Graduação em Saúde Coletiva, Universidade Federal de Mato Grosso. Av. Fernando Correa da Costa 2367. 78060-900 Cuiabá MT Brasil.
- Secretaria de Estado de Saúde de Mato Grosso. Cuiabá MT Brasil
| | - Rita Adriana Gomes de Souza
- Programa de Pós-Graduação em Saúde Coletiva, Universidade Federal de Mato Grosso. Av. Fernando Correa da Costa 2367. 78060-900 Cuiabá MT Brasil.
| | - Mário Ribeiro Alves
- Programa de Pós-Graduação em Saúde Coletiva, Universidade Federal de Mato Grosso. Av. Fernando Correa da Costa 2367. 78060-900 Cuiabá MT Brasil.
| | | | - Amanda Cristina de Souza Andrade
- Programa de Pós-Graduação em Saúde Coletiva, Universidade Federal de Mato Grosso. Av. Fernando Correa da Costa 2367. 78060-900 Cuiabá MT Brasil.
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Martínez-Ciarpaglini C, Barros R, Caballero C, Boggino H, Alarcón-Molero L, Peleteiro B, Ruiz-García E, Fernandez-Figueroa E, Herrera-Goepfert R, Díaz-Romero C, Ferreira R, Groen-van Schooten TS, Gauna C, Pereira R, Cantero D, Lezcano H, Esteso F, O Connor J, Riquelme A, Owen GI, Garrido M, Roa JC, Ruiz-Pace F, Vivancos A, Diez-García M, Alsina M, Matito J, Martin A, Gómez M, Castillo E, Vila M, Santos-Antunes J, Costa A, Lordick F, Farrés J, Palomar-De Lucas B, Cabeza-Segura M, Villagrasa R, Jimenez-Martí E, Miralles-Marco A, Dienstmann R, Derks S, Figueiredo C, Cervantes A, Carneiro F, Fleitas-Kanonnikoff T. Comprehensive histopathological analysis of gastric cancer in European and Latin America populations reveals differences in PDL1, HER2, p53 and MUC6 expression. Gastric Cancer 2025; 28:160-173. [PMID: 39755998 PMCID: PMC11842524 DOI: 10.1007/s10120-024-01578-3] [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: 08/24/2024] [Accepted: 12/16/2024] [Indexed: 01/07/2025]
Abstract
INTRODUCTION Gastric cancer (GC) burden is currently evolving with regional differences associated with complex behavioural, environmental, and genetic risk factors. The LEGACy study is a Horizon 2020-funded multi-institutional research project conducted prospectively to provide comprehensive data on the tumour biological characteristics of gastroesophageal cancer from European and LATAM countries. MATERIAL AND METHODS Treatment-naïve advanced gastroesophageal adenocarcinoma patients were prospectively recruited in seven European and LATAM countries. Formalin-fixed paraffin-embedded primary tumour endoscopic biopsy samples were collected and submitted for central morphological and immunohistochemical characterization and TP53 molecular assessment and Helicobacter pylori infection. RESULTS A total of 259 patients were included in the study: 137 (53%) from LATAM and 122 (47%) from Europe. Significant biological differences were detected between European and LATAM patients. Low representation of chromosomal instability (CIN) and HER2 positive cases were found in LATAM. MUC6 and PD-L1 were more frequently overexpressed in European cases, showing a significant correlation across the entire study population, with this association being especially pronounced in MMRdeficient cases. Both TP53 mutation by next-generation sequencing and p53 immunohistochemical aberrant pattern were linked with features associated with chromosomal instability. No regional differences were observed in H. pylori prevalence or abundance, indicating that the afore mentioned variations cannot be attributed to this factor. CONCLUSION Our findings underscore a need for region-specific approaches in gastroesophageal cancer diagnosis and treatment. MUC6 emerges as a putative immune regulator that needs further investigation. Research tailored to the unique biological profiles in different global regions is crucial to effectively address the observed disparities.
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Affiliation(s)
- Carolina Martínez-Ciarpaglini
- Department of Pathology, Hospital Clinico Universitario, INCLIVA, Biomedical Research Institute, University of Valencia, Valencia, Spain
| | - Rita Barros
- Ipatimup, Institute of Molecular Pathology and Immunology of the University of Porto, Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal
- i3S-Instituto de Investigação e Inovação em Saúde, Universidade Do Porto, Porto, Portugal
- Faculty of Medicine of the University of Porto, Porto, Portugal
- Department of Pathology, Unidade Local de Saúde São João, Porto, Portugal
| | | | - Hugo Boggino
- Department of Pathology, GENPAT, Asunción, Paraguay
| | - Lorena Alarcón-Molero
- Department of Pathology, Hospital Clinico Universitario, INCLIVA, Biomedical Research Institute, University of Valencia, Valencia, Spain
- Department of Pathology, Hospital General de Valdepeñas, Valdepeñas, Spain
| | - Bárbara Peleteiro
- Hospital Epidemiology Center, University Hospital Center of São João, Porto, Portugal
- Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine, University of Porto, Porto, Portugal
- EPIUnit-Institute of Public Health, University of Porto, Porto, Portugal
- Laboratory for Integrative and Translational Research in Population Health (ITR), University of Porto, Porto, Portugal
| | - Erika Ruiz-García
- Departamento de Tumores de Tubo Digestivo, Instituto Nacional de Cancerología, Mexico City, México
- Laboratorio de Medicina Traslacional, Instituto Nacional de Cancerología, Mexico City, México
| | - Edith Fernandez-Figueroa
- Núcleo B de Innovación en Medicina de Precisión, Instituto Nacional de Medicina Genómica, Mexico City, México
| | | | - Consuelo Díaz-Romero
- Departamento de Oncología Médica, Instituto Nacional de Cancerología, Mexico City, México
| | - Rui Ferreira
- Ipatimup, Institute of Molecular Pathology and Immunology of the University of Porto, Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal
- Microbes & Cancer. i3S, Instituto de Investigação e Inovação em Saúde, , Rua Alfredo Allen, 208, 4200-135, Porto, Portugal
| | - Tessa S Groen-van Schooten
- Department of Medical Oncology, Amsterdam University Medical Center (UMC) Location Vrije Universiteit Amsterdam, Amsterdam, Netherlands
- Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, Netherlands
- Oncode Institute, Amsterdam, The Netherlands
| | - Cinthia Gauna
- Medical Oncology Department, Instituto de Previsión Social, Asunción, Paraguay
| | - Rita Pereira
- Medical Oncology Department, Instituto de Previsión Social, Asunción, Paraguay
| | - Daniel Cantero
- Department of Gastroenterology, Instituto de Previsión Social, Asunción, Paraguay
| | - Horacio Lezcano
- Pathology Department, Instituto de Previsión Social, Asunción, Paraguay
| | - Federico Esteso
- Medical Oncology Department, Instituto Alexander Fleming, Buenos Aires, Argentina
| | - Juan O Connor
- Medical Oncology Department, Instituto Alexander Fleming, Buenos Aires, Argentina
| | - Arnoldo Riquelme
- Department of Gastroenterology, Faculty of MedicineCenter for Prevention and Control of Cancer (CECAN), Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Gareth I Owen
- Faculty of Biological Sciences & Faculty of Medicine, Millennium Institute for Immunology and ImmunotherapyCenter for Prevention and Control of Cancer (CECAN), Advance Center for Chronic Disease (ACCDIS), Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Marcelo Garrido
- Centro de Oncología de Precisión, Universidad Mayor, Santiago, Chile
| | - Juan Carlos Roa
- Department of Pathology. Faculty of Medicine. Pontificia, Universidad Católica de Chile Santiago, Santiago, Chile
| | - Fiorella Ruiz-Pace
- Oncology Data Science, Valld`Hebron Institute of Oncology, Barcelona, Spain
| | - Ana Vivancos
- Cancer Genomics Lab, Valld`Hebron Institute of Oncology, Barcelona, Spain
| | - Marc Diez-García
- Medical Oncology Department, Valld`Hebron Institute of Oncology, Barcelona, Spain
| | - Maria Alsina
- Medical Oncology Department, Valld`Hebron Institute of Oncology, Barcelona, Spain
- Hospital Universitario de Navarra, Navarrabiomed-IdiSNA, Pamplona, Spain
| | - Judit Matito
- Cancer Genomics Lab, Valld`Hebron Institute of Oncology, Barcelona, Spain
| | - Agatha Martin
- Cancer Genomics Lab, Valld`Hebron Institute of Oncology, Barcelona, Spain
| | - Marina Gómez
- Cancer Genomics Lab, Valld`Hebron Institute of Oncology, Barcelona, Spain
| | - Ester Castillo
- Cancer Genomics Lab, Valld`Hebron Institute of Oncology, Barcelona, Spain
| | - Maria Vila
- Cancer Genomics Lab, Valld`Hebron Institute of Oncology, Barcelona, Spain
| | - João Santos-Antunes
- Department of Gastroenterology, Unidade Local de Saúde São João, Porto, Portugal
| | - Andreia Costa
- Department of Oncology, Unidade Local de Saúde São João, Porto, Portugal
| | - Florian Lordick
- Department of Medicine (Oncology, Gastroenterology, Hepatology, and Pulmonology), Comprehensive Cancer Center Central Germany (CCCG), University of Leipzig Medical Center, Leipzig, Germany
| | | | - Brenda Palomar-De Lucas
- Department of Medical Oncology, Hospital Clinico Universitario, INCLIVA, Biomedical Research Institute, University of Valencia, Avenida Menendez Pelayo nro 4 accesorio, Valencia, Spain
| | - Manuel Cabeza-Segura
- Department of Medical Oncology, Hospital Clinico Universitario, INCLIVA, Biomedical Research Institute, University of Valencia, Avenida Menendez Pelayo nro 4 accesorio, Valencia, Spain
| | - Rosanna Villagrasa
- Department of Gastroenterology, Hospital Clínico Universitario de Valencia, Valencia, Spain
| | - Elena Jimenez-Martí
- Department of Medical Oncology, Hospital Clinico Universitario, INCLIVA, Biomedical Research Institute, University of Valencia, Avenida Menendez Pelayo nro 4 accesorio, Valencia, Spain
| | - Ana Miralles-Marco
- Department of Medical Oncology, Hospital Clinico Universitario, INCLIVA, Biomedical Research Institute, University of Valencia, Avenida Menendez Pelayo nro 4 accesorio, Valencia, Spain
| | - Rodrigo Dienstmann
- Oncology Data Science, Valld`Hebron Institute of Oncology, Barcelona, Spain
| | - Sarah Derks
- Department of Medical Oncology, Amsterdam University Medical Center (UMC) Location Vrije Universiteit Amsterdam, Amsterdam, Netherlands
- Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, Netherlands
- Oncode Institute, Amsterdam, The Netherlands
| | - Ceu Figueiredo
- Ipatimup, Institute of Molecular Pathology and Immunology of the University of Porto, Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal
- i3S-Instituto de Investigação e Inovação em Saúde, Universidade Do Porto, Porto, Portugal
- Faculty of Medicine of the University of Porto, Porto, Portugal
| | - Andrés Cervantes
- Department of Medical Oncology, Hospital Clinico Universitario, INCLIVA, Biomedical Research Institute, University of Valencia, Avenida Menendez Pelayo nro 4 accesorio, Valencia, Spain
- Department of Gastroenterology, Hospital Clínico Universitario de Valencia, Valencia, Spain
- CiberOnc. Carlos III Institute, Madrid, Spain
| | - Fátima Carneiro
- Ipatimup, Institute of Molecular Pathology and Immunology of the University of Porto, Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal
- i3S-Instituto de Investigação e Inovação em Saúde, Universidade Do Porto, Porto, Portugal
- Faculty of Medicine of the University of Porto, Porto, Portugal
- Department of Pathology, Unidade Local de Saúde São João, Porto, Portugal
| | - Tania Fleitas-Kanonnikoff
- Department of Medical Oncology, Hospital Clinico Universitario, INCLIVA, Biomedical Research Institute, University of Valencia, Avenida Menendez Pelayo nro 4 accesorio, Valencia, Spain.
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Le NT, Van Nguyen T, Le LT, Nguyen LC. Dietary protein intake and stomach cancer, insights from a case-control study. Sci Rep 2025; 15:6909. [PMID: 40011552 DOI: 10.1038/s41598-024-80793-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Accepted: 11/21/2024] [Indexed: 02/28/2025] Open
Abstract
Studies on the role of protein intake in the development of stomach cancer (SC) remain controversial. This study examines the relationship between protein intake from whole foods and SC in a Vietnamese population. A case-control study was designed in the university hospitals in Hanoi, Vietnam, from 2003 to 2019. Participants included 1182 SC cases and 2995 controls. Of the participants, 2,580 were men, and 1,597 were women. Protein intake was assessed using a validated semi-quantitative food frequency questionnaire. The odds ratio and 95% confidence interval (OR, 95%CI) examined the risk of SC associated with total protein and subgroups of mammal-animals and fish-poultry protein. Overall protein intake was negatively associated with SC (fifth vs. first quintile: OR (95%CI): 0.41 (0.32, 0.51). The dose-response relationship was also observed per increment quintile, OR (95%CI): 0.81 (0.77, 0.86) for both genders, OR (95%CI): 0.82 (0.77, 0.88) in men, OR (95%CI): 0.80 (0.73, 0.87) in women, OR (95%CI): 0.82 (0.77, 0.86) for noncardiac and OR (95%CI): 0.79 (0.63, 1.00) for cardiac stomach cancer. The beneficial effects of SC remained for the protein sources from mammal-animals and fish-poultry protein. The significant inverse association between protein intake remained in the ever and never tobacco smoking, no-alcohol use and alcohol use, blood group A and AB, and O, H. Pylori infected group, and the status of body-mass-index. The findings suggest that a high-protein diet is associated with lower SC risk. Further investigation is warranted to understand the beneficial effect of protein intake against stomach cancer.
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Affiliation(s)
- Ngoan Tran Le
- Institute of Research and Development, Duy Tan University, Da Nang City, Vietnam.
- Department of Occupational Health, Institute for Preventive Medicine and Public Health, Hanoi Medical University, Ha Noi City, Vietnam.
| | - Tai Van Nguyen
- School of Medicine, International University of Health and Welfare, Narita City, Japan
| | - Linh Thuy Le
- Laboratory of Embryology and Genetics of Human Malformation, Imagine Institute, INSERM UMR, Paris City, France
| | - Long Cong Nguyen
- Gastroenterology and Hepatology Center, Bach Mai Hospital, Ha Noi City, Vietnam
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Darbandi M, Khorrami Z, Karamoozian A, Aboubakri O, Miryan M, Rezakhani L, Shadmani FK. A comparison of the burden of cancers between 1990 and 2019 in Iran: A national and subnational study. PLoS One 2025; 20:e0309699. [PMID: 39999060 PMCID: PMC11856284 DOI: 10.1371/journal.pone.0309699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Accepted: 08/17/2024] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND Cancer is a rapidly increasing global problem, and one of the leading causes of burden and mortality. This study aims to compare the burden of cancer in Iran between the year 1990 and 2019. METHODS We used Global Burden of Disease data on cancer from 1990 to 2019 by province, year, age group, and sex. We then estimated the trend of age standardized mortality and Disability-Adjusted Life Years (DALYs) of the cancers by sex. Age pattern and geographical variation in the ranking of cancers were assessed at national and sub-national levels from 1990 to 2019. RESULTS The mortality rate decreased from 102 (95% UI: 91, 111) to 96 (95% UI: 88, 103) per 100000 population. Additionally, the DALYs rates decreased from 2619 (95% UI: 2357, 2852) to 2321 (95% UI: 2116, 2497) per 100000 between 1990 and 2019. Both of the mortality and DALYs rate from cancers increased with age. These indicators were significantly higher in men than in women across all age groups. Consequently, the mortality rate and DALYs per 100,000 of cancers were higher in the northwest and northeast of Iran. Notably, stomach cancer was identified as the leading cause of cancer mortality in 23 provinces of Iran in 2019. The highest percentage change of DALYs per 100,000 rate between 1990 and 2019 was observed for malignant skin melanoma, stomach cancer, and cervical cancers with rate of -41.1, -40.1, and -38.4, respectively. CONCLUSION Overall, the mortality and DALYs per 100,000 rates of all cancers for both sexes in Iran have decreased between 1990 and 2019. However, there is an increasing trend in types of cancers, such as pancreatic, ovarian, and breast cancers.
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Affiliation(s)
- Mitra Darbandi
- Research Center for Environmental Determinants of Health (RCEDH), Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Zahra Khorrami
- Ophthalmic Epidemiology Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Karamoozian
- Modeling in Health Research Center, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran
- Department of Biostatistics and Epidemiology, Kerman University of Medical Sciences, Kerman, Iran
| | - Omid Aboubakri
- Environmental Health Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Mahsa Miryan
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Leila Rezakhani
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Fatemeh Khosravi Shadmani
- Research Center for Environmental Determinants of Health (RCEDH), Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
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Paridar Y, Hosseinpour H, Mard-Soltani M, Pouria Mehr S, Shakerian N, Alinezhad Dezfuli D, Khalili S, Abyaz MR. Evaluation of the clinical significance of BTG1 gene expression and pepsinogen in serum and cancerous tissue and gastric atrophy. Arch Physiol Biochem 2025:1-10. [PMID: 39988895 DOI: 10.1080/13813455.2025.2458560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 12/20/2024] [Accepted: 01/21/2025] [Indexed: 02/25/2025]
Abstract
INTRODUCTION This study aimed to assess the expression changes of BTG1, PGI, and PGII in tissues and serum of patients with gastric cancer, atrophic gastritis, and healthy individuals. METHODS QRT-PCR was used to measure BTG1, PGI, and PGII expression in 30 cancers, 30 atrophic gastritis, and 30 healthy tissue samples. Serum levels of PGI and PGII were measured using ELISA. Statistical tests included the Mann-Whitney U and independent T-test. Covariates like tumour stage and H. pylori status were considered. RESULTS BTG1 expression was significantly lower in cancer and gastritis tissues. Serum PGI and PGII levels were significantly reduced in cancer patients (P ≤ 0.001). DISCUSSION The PGI/PGII ratio in serum emerged as a strong non-invasive biomarker for distinguishing cancer from healthy individuals. While BTG1 provides insights into gastric carcinogenesis, its clinical utility is limited due to the need for tissue samples. The serum-based PGI/PGII ratio shows greater promise as a non-invasive screening tool for GC.
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Affiliation(s)
- Yousef Paridar
- Gastroenterology Clinic, Dezful University of Medical Sciences, Dezful, Iran
| | - Homa Hosseinpour
- Department of Pathology, Faculty of Medical Sciences, Dezful University of Medical Sciences, Dezful, Iran
| | - Maysam Mard-Soltani
- Department of Clinical Biochemistry, Faculty of Medical Sciences, Dezful University of Medical Sciences, Dezful, Iran
| | - Somayeh Pouria Mehr
- Department of Clinical Biochemistry, Faculty of Medical Sciences, Dezful University of Medical Sciences, Dezful, Iran
| | - Neda Shakerian
- Department of Clinical Biochemistry, Faculty of Medical Sciences, Dezful University of Medical Sciences, Dezful, Iran
| | - Davood Alinezhad Dezfuli
- Department of Clinical Biochemistry, Faculty of Medical Sciences, Dezful University of Medical Sciences, Dezful, Iran
| | - Saeed Khalili
- Department of Biology Sciences, Shahid Rajaee Teacher Training University, Tehran, Iran
| | - Mohammad Reza Abyaz
- Department of Pathology, Faculty of Medical Sciences, Dezful University of Medical Sciences, Dezful, Iran
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Miciak M, Jurkiewicz K, Dzierżek P, Rudno-Rudzińska J, Kielan W. Prognostic Significance of Lymph Node Ratio (LNR) in Gastric Cancer in Predicting Postoperative Complications and Survival: A Single-Center Study. Cancers (Basel) 2025; 17:743. [PMID: 40075592 PMCID: PMC11899347 DOI: 10.3390/cancers17050743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2025] [Revised: 02/18/2025] [Accepted: 02/21/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND/OBJECTIVES The Lymph Node Ratio (LNR) index is the proportion of lymph nodes with present metastases to lymph nodes removed and examined. This is an additionally established parameter for predicting the prognosis of gastric cancer patients. The most popular cancer classification, TNM, describes only the number of affected lymph nodes. It can result in a negative overestimation of the prognosis of patients with gastric cancer if the number of nodes examined is relatively limited. METHODS In this study, we retrospectively analyzed 194 patients diagnosed with gastric cancer operated on between 2017 and 2021 at the Clinical Department of Oncological Surgery, University Centre of General and Oncological Surgery of the University Clinical Hospital in Wroclaw. In total, 133 patients underwent gastrectomy with D2 lymphadenectomy and 61 remaining patients had the resection procedure abandoned due to an unresectable lesion. The LNR index was calculated based on histopathological examination, and postoperative complications were assessed using the Clavien-Dindo (C-D) scale. Statistical analysis was performed regarding the dependence of LNR on the following patient characteristics: sex, age, TNM features, tumor stage, tumor location, performed procedure, chemotherapy application, C-D complication rate, and survival rate. RESULTS The value of the LNR index significantly depends on TNM features (p < 0.05), clinical tumor stage (p < 0.05), and patient survival (p < 0.05), while no statistically significant relationship with C-D complication rate was demonstrated. CONCLUSIONS The LNR index is a relevant parameter in predicting prognosis and survival time in gastric cancer patients, but future studies on larger and differentiated groups of patients could further confirm its usefulness in the development of guidelines.
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Affiliation(s)
- Michał Miciak
- Clinical Department of Oncological Surgery, University Centre of General and Oncological Surgery, Faculty of Medicine, Wroclaw Medical University, 50-556 Wrocław, Poland; (K.J.); (J.R.-R.); (W.K.)
| | | | - Przemysław Dzierżek
- Clinical Department of Oncological Surgery, University Centre of General and Oncological Surgery, Faculty of Medicine, Wroclaw Medical University, 50-556 Wrocław, Poland; (K.J.); (J.R.-R.); (W.K.)
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10
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Liang GZ, Li XS, Hu ZH, Xu QJ, Wu F, Wu XL, Lei HK. Development and validation of a nomogram model for predicting overall survival in patients with gastric carcinoma. World J Gastrointest Oncol 2025; 17:95423. [PMID: 39958550 PMCID: PMC11755997 DOI: 10.4251/wjgo.v17.i2.95423] [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: 04/10/2024] [Revised: 10/01/2024] [Accepted: 11/06/2024] [Indexed: 01/18/2025] Open
Abstract
BACKGROUND The prevalence and mortality rates of gastric carcinoma are disproportionately elevated in China, with the disease's intricate and varied characteristics further amplifying its health impact. Precise forecasting of overall survival (OS) is of paramount importance for the clinical management of individuals afflicted with this malignancy. AIM To develop and validate a nomogram model that provides precise gastric cancer prevention and treatment guidance and more accurate survival outcome prediction for patients with gastric carcinoma. METHODS Data analysis was conducted on samples collected from hospitalized gastric cancer patients between 2018 and 2020. Least absolute shrinkage and selection operator, univariate, and multivariate Cox regression analyses were employed to identify independent prognostic factors. A nomogram model was developed to predict gastric cancer patient outcomes. The model's predictability and discriminative ability were evaluated via receiver operating characteristic curves. To evaluate the clinical utility of the model, Kaplan-Meier and decision curve analyses were performed. RESULTS A total of ten independent prognostic factors were identified, including body mass index, tumor-node-metastasis (TNM) stage, radiation, chemotherapy, surgery, albumin, globulin, neutrophil count, lactate dehydrogenase, and platelet-to-lymphocyte ratio. The area under the curve (AUC) values for the 1-, 3-, and 5-year survival prediction in the training set were 0.843, 0.850, and 0.821, respectively. The AUC values were 0.864, 0.820, and 0.786 for the 1-, 3-, and 5-year survival prediction in the validation set, respectively. The model exhibited strong discriminative ability, with both the time AUC and time C-index exceeding 0.75. Compared with TNM staging, the model demonstrated superior clinical utility. Ultimately, a nomogram was developed via a web-based interface. CONCLUSION This study established and validated a novel nomogram model for predicting the OS of gastric cancer patients, which demonstrated strong predictive ability. Based on these findings, this model can aid clinicians in implementing personalized interventions for patients with gastric cancer.
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Affiliation(s)
- Guan-Zhong Liang
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, China
| | - Xiao-Sheng Li
- Chongqing Cancer Multi-omics Big Data Application Engineering Research Center, Chongqing University Cancer Hospital, Chongqing 400030, China
| | - Zu-Hai Hu
- Department of Health Statistics, School of Public Health, Chongqing Medical University, Chongqing 400016, China
| | - Qian-Jie Xu
- Department of Health Statistics, School of Public Health, Chongqing Medical University, Chongqing 400016, China
| | - Fang Wu
- Research Center for Medicine and Social Development, School of Public Health, Chongqing Medical University, Chongqing 400016, China
| | - Xiang-Lin Wu
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, China
| | - Hai-Ke Lei
- The Research Center of Big Data, Chongqing University Cancer Hospital, Chongqing 400030, China
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11
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Wiklund AK, Santoni G, Yan J, Radkiewicz C, Xie S, Birgisson H, Ness-Jensen E, von Euler-Chelpin M, Kauppila JH, Lagergren J. Risk of Gastric Adenocarcinoma After Eradication of Helicobacter pylori. Gastroenterology 2025:S0016-5085(25)00356-7. [PMID: 39924057 DOI: 10.1053/j.gastro.2025.01.239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 01/20/2025] [Accepted: 01/21/2025] [Indexed: 02/11/2025]
Abstract
BACKGROUND AND AIMS Helicobacter pylori infection of the stomach is the main risk factor for gastric noncardia adenocarcinoma; however, less is known on how eradication of H pylori influences the risk of this tumor over time, particularly in Western populations. The aim of this study was to delineate how the risk of gastric noncardia adenocarcinoma develops over time after H pylori eradication treatment in a Western population compared with the background population. METHODS This population-based cohort study included all adults having received H pylori eradication treatment between 1995 and 2019 in any of the Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden). Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated by comparing the gastric noncardia adenocarcinoma incidence in the study cohort with the incidence in the background population of the same age, sex, calendar period, and country. Time trends in SIR were assessed using Poisson regression. RESULTS Among 659,592 participants having received H pylori eradication treatment, contributing 5,480,873 person-years at risk, 1311 developed gastric noncardia adenocarcinoma. During up to 24 years of follow-up, the SIR was initially higher than the background population (SIR, 2.27; 95% CI 2.10-2.44, 1-5 years after treatment), and then gradually decreased over time and approached the level of the background population from 11 years after treatment (SIR, 1.11; 95% CI 0.98-1.27, 11-24 years after treatment). CONCLUSION This study revealed a decreasing incidence of gastric noncardia adenocarcinoma after H pylori eradication treatment in 5 Western populations. The risk became virtually similar to the background population from 11 years after treatment.
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Affiliation(s)
- Anna-Klara Wiklund
- Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden; Department of Surgery, Stockholm South Hospital, Stockholm, Sweden; Department of Clinical Science and Education South Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Giola Santoni
- Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden
| | - Jane Yan
- Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Cecilia Radkiewicz
- Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden
| | - Shaohua Xie
- Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden
| | | | - Eivind Ness-Jensen
- Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden; HUNT Research Center, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim/Levanger, Norway; Medical Department, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway
| | | | - Joonas H Kauppila
- Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden; Department of Surgery, Oulu University Hospital and University of Oulu, Oulu, Finland
| | - Jesper Lagergren
- Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden; School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom.
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12
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Kossenas K, Moutzouri O, Georgopoulos F. Evaluating the safety of robotic total gastrectomy with D2 lymphadenectomy for gastric cancer against the conventional laparoscopic approach: a systematic review and meta-analysis. J Robot Surg 2025; 19:59. [PMID: 39899136 DOI: 10.1007/s11701-025-02219-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 01/22/2025] [Indexed: 02/04/2025]
Abstract
Gastric cancer poses a significant global health challenge, necessitating effective surgical interventions. A critical gap in the literature exists, as most studies do not differentiate between various surgical approaches, i.e., total, distal, and subtotal gastrectomy, and level of lymphadenectomy, when comparing robotic to conventional laparoscopic gastrectomy. This leads to a lack of clear evidence regarding the safety and efficacy of robotic total gastrectomy (RTG) specifically in the context of total gastrectomy with D2 lymphadenectomy.This systematic review and meta-analysis evaluates the safety of RTG with D2 lymphadenectomy compared to conventional laparoscopic total gastrectomy (LTG). A literature search was conducted up to November 1, 2024, following PRISMA guidelines. Eligible studies included studies comparing RTG and LTG, focusing on anastomotic leakage, Clavien-Dindo Grade ≥ III complications, conversion rates, mortality, overall complications, and reoperation rates. Data were synthesized using odds ratios (OR) and weighted mean differences (WMD), with statistical heterogeneity assessed using the I2 statistic. Five studies comprising 1131 patients (432 RTG, 700 LTG) were included. No significant differences were found in the following outcomes: anastomotic leakage (OR = 0.79 [95% CI: 0.35, 1.78], I2 = 0%, P = 0.57), Clavien-Dindo Grade ≥ III complications (OR = 0.86 [95% CI: 0.51, 1.45], I2 = 0%, P = 0.56), conversion to open surgery (OR = 0.34 [95% CI: 0.10, 1.18], I2 = 0%, P = 0.09), mortality (OR = 1.78 [95% CI: 0.23, 13.48], I2 = 0%, P = 0.58), overall complications (OR = 0.84 [95% CI: 0.62, 1.14], I2 = 0%, P = 0.26), and reoperation rates (OR = 0.88 [95% CI: 0.29, 2.67], I2 = 0%, P = 0.82). Sensitivity analysis proves the robustness of the findings. The analysis shows no significant differences in safety outcomes between RTG and LTG for gastric cancer, indicating both techniques are comparable. RTG may be a viable alternative to LTG, especially in centers with appropriate robotic capabilities. Further research is warranted to investigate long-term outcomes and the learning curve of robotic surgery.PROSPERO Registration: CRD42024606570.
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Affiliation(s)
- Konstantinos Kossenas
- Department of Basic and Clinical Sciences, University of Nicosia Medical School, 21 Ilia Papakyriakou, 2414 Engomi, P.O. Box 24005, 1700, Nicosia, Cyprus.
| | - Olga Moutzouri
- Department of Basic and Clinical Sciences, University of Nicosia Medical School, 21 Ilia Papakyriakou, 2414 Engomi, P.O. Box 24005, 1700, Nicosia, Cyprus
| | - Filippos Georgopoulos
- Head of Interventional Gastroenterology and Hepatology, Al Zahra Hospital, Dubai, UAE
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13
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Kalra A, Meltzer SJ. The Role of DNA Methylation in Gastrointestinal Disease: An Expanded Review of Malignant and Nonmalignant Gastrointestinal Diseases. Gastroenterology 2025; 168:245-266. [PMID: 38971197 PMCID: PMC11698954 DOI: 10.1053/j.gastro.2024.07.001] [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: 10/10/2023] [Revised: 06/20/2024] [Accepted: 07/01/2024] [Indexed: 07/08/2024]
Abstract
Esophageal, colorectal, pancreatic, hepatocellular, and gastric cancer together impact millions of patients worldwide each year, with high overall mortality rates, and are increasing in incidence. Additionally, premalignant gastrointestinal diseases, such as Barrett's esophagus and inflammatory bowel disease, are also increasing in incidence. However, involvement of aberrant DNA methylation in these diseases is incompletely understood, especially given recent research advancements in this field. Here, we review knowledge of this epigenetic mechanism in gastrointestinal preneoplasia and neoplasia, considering mechanisms of action, genetic and environmental factors, and 5'-C-phosphate-G-3' island methylator phenotype. We also highlight developments in translational research, focusing on genomic-wide data, methylation-based biomarkers and diagnostic tests, machine learning, and therapeutic epigenetic strategies.
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Affiliation(s)
- Andrew Kalra
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Stephen J Meltzer
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
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14
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Cayuela L, Peiró Villalba C, Flox-Benítez G, Cayuela A. Divergent trends in gastric cancer incidence by sex and age in Spain (1990-2019). REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2025; 117:68-75. [PMID: 39324626 DOI: 10.17235/reed.2024.10443/2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/27/2024]
Abstract
OBJECTIVE to investigate trends in gastric cancer (GC) incidence in Spain from 1990 to 2019, analyzing variations by sex and age. METHOD GC incidence data from the Global Burden of Disease database and population data from the Spanish National Institute of Statistics were used to calculate age-specific and age-standardized incidence rates (ASIR) with the European population as the reference. Temporal trends by sex and age groups were analyzed using joinpoint regression. RESULTS while the total number of cases increased slightly, ASIR showed a consistent annual decrease of 1.8 % for both men and women. Both sexes experienced this increase in total cases (women: 4,023 to 4,359; men: 6,243 to 6,591). Men consistently had a higher GC burden compared to women (approximately 2.2:1 ratio). Younger adults (< 35 years) of both sexes showed significant decreases in ASIR. However, the joinpoint analysis revealed a recent increase in young men (25-34 years) during the period 2014-2019. Adults aged 35-64 showed a decrease in ASIR for both sexes, with a slightly steeper decline in men. Adults over 65 had a similar decrease in ASIR for both sexes, but the joinpoint analysis suggests different patterns within this age group. CONCLUSION our study revealed a decline in overall age-adjusted GC incidence in Spain. However, the recent rise observed in young men warrants further investigation to understand potential risk factors in this specific population group.
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Affiliation(s)
- Lucía Cayuela
- Internal Medicine, Hospital Universitario Severo Ochoa
| | | | | | - Aurelio Cayuela
- Public Health, Prevention and Health Promotion, Hospital Universitario Virgen de Valme, España
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15
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Yu AT, Sarfaty E, Pahlkotter M, Cohen NA. Open Gastric Surgery for Gastric Cancer. Surg Clin North Am 2025; 105:1-13. [PMID: 39523066 DOI: 10.1016/j.suc.2024.06.002] [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] [Indexed: 11/16/2024]
Abstract
Gastric cancer is a leading cause of cancer and cancer-related mortality worldwide, especially in East Asia. It is often diagnosed at an advanced stage, which carries a poor prognosis. Patients with advanced gastric cancer typically receive systemic therapy and best supportive care. For patients with locally advanced gastric cancer, a combination of systemic therapy and surgical resection is recommended, while surgical resection-alone is recommended for patients with early-stage localized tumors. Surgical resection, including total gastrectomy, distal gastrectomy, and proximal gastrectomy, is recommended for resection of localized tumors based on tumor location. Herein, the authors provide an overview of open gastrectomy resection and reconstruction techniques.
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Affiliation(s)
- Allen T Yu
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Elad Sarfaty
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Maranda Pahlkotter
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Noah A Cohen
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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16
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Kim D, Lee MK. Effectiveness of Postoperative Dietary Intervention in Patients with Gastric Cancer who Underwent Gastrectomy: Quasi-Experimental Study Design. Semin Oncol Nurs 2025; 41:151797. [PMID: 39710557 DOI: 10.1016/j.soncn.2024.151797] [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: 08/02/2024] [Revised: 11/30/2024] [Accepted: 12/03/2024] [Indexed: 12/24/2024]
Abstract
OBJECTIVES This article aims to investigate the effects of a postoperative dietary intervention on fatigue, self-efficacy in managing gastrointestinal side effects, self-efficacy for nutritional management, self-care activity, and unmet nursing needs among patients with gastric cancer who have undergone gastrectomy. METHODS We used a quasi-experimental study design (nonequivalent control group pretest-posttest). Data were collected from 59 patients with gastric cancer (30 in the experimental group and 29 in the control patients) hospitalized for gastrectomy in Daegu, South Korea. The control group completed a preintervention survey, received routine care, and then completed a postintervention survey. After the control group finished their routine care and tests, the experimental group received a postoperative dietary intervention. This intervention included individual face-to-face education and telephone counseling on managing gastrectomy side effects, eating methods to prevent symptoms, foods to avoid, ways to consume sufficient calories, maintaining a balanced diet, and pledge writing. The control group served as a waitlist control. After all interventions and tests for the experimental group were completed, the same dietary intervention was offered to the control group upon their request. This experimental study was conducted from June 2021 to February 2023. RESULTS Compared with the control group, the experimental group showed significant improvements in fatigue (P = .005), self-efficacy in managing gastrointestinal side effects (P < .001), self-efficacy for nutritional management (P = .03), self-care activity (P < .001), and unmet nursing needs (P < .001). CONCLUSION Postoperative dietary interventions contribute to improving self-efficacy, fatigue levels, and self-care activity among patients with gastric cancer. IMPLICATIONS FOR NURSING PRACTICE Upon discharge, implementing a needs-based and loss-framed message-based dietary intervention, alongside routine discharge education, for patients who underwent gastrectomy for gastric cancer can enhance fatigue levels, self-efficacy in managing nutrition and gastrointestinal side effects, self-care activity, and unmet nursing needs.
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Affiliation(s)
- Dahye Kim
- College of Nursing, Kyungpook National University Graduate School
| | - Myung Kyung Lee
- College of Nursing, Research Institute of Nursing Innovation, Kyungpook National University, Daegu, South Korea.
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17
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Loarca-Piña G, Manríquez-Núñez J, Ramos-Gómez M, Recio I, Sánchez-Quezada V. Oral-gastric digestion effect of emulsion-type ingredient of avocado seed and cytotoxic potential in gastric cancer cell. Food Res Int 2025; 202:115705. [PMID: 39967159 DOI: 10.1016/j.foodres.2025.115705] [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: 10/24/2024] [Revised: 12/29/2024] [Accepted: 01/05/2025] [Indexed: 02/20/2025]
Abstract
The incorporation of plant-derived bioactive compounds into the food matrix is growing due to their benefits in improving human health. Agro-industrial avocado by-products are usually inexperienced waste and represent a 22-30% total fruit weight; however, they stand out for being high in bioactive and functional components such as lipid compounds, phenolic compounds, oxalates, and fiber, among others; Bioactive compound to be characteristic to preventive chronic disease proprieties. Besides, gastric cancer has anintermediate prevalence of 10-20 in 100,000 people, and isthe fifth most common cancer worldwide; health institutions recommend consuming fruits and vegetables as an effective strategy because their bioactive compounds exert chemopreventive activity. However, there is a knowledge gap regarding the bioaccessibility and chemical changes of phenolic compounds in ingredients and their implications in gastric cancer during the digestive process, mainly the gastric phase at different times. This study determined the bioaccessibility of phenolic compounds and evaluated the cytotoxicity in a transformed gastric cell line (CRL-1739) during oral-gastric digestion of ingredients from avocado seed. Principal phenolic compounds in the ingredient show high concentrations of catechin, rutin, ellagic, and chlorogenic acid; The phenolic compounds are more bioaccessible in gastric phases of 10 and 25 min, attributed to acid hydrolysis. The ingredient exhibited a maximum cytotoxicity potential in the gastric cancer cell line with the gastric phase at 10 min. Hence the ingredient from avocado seed has possible functional potential in gastric digestion.
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Affiliation(s)
- Guadalupe Loarca-Piña
- Programa Doctorado en Ciencias de los Alimentos, Research and Graduate Studies in Food Science, School of Chemistry, Universidad Autónoma de Querétaro, Querétaro, México
| | - Josué Manríquez-Núñez
- Programa Doctorado en Ciencias de los Alimentos, Research and Graduate Studies in Food Science, School of Chemistry, Universidad Autónoma de Querétaro, Querétaro, México
| | - Minerva Ramos-Gómez
- Programa Doctorado en Ciencias de los Alimentos, Research and Graduate Studies in Food Science, School of Chemistry, Universidad Autónoma de Querétaro, Querétaro, México
| | - Isidra Recio
- Instituto de Investigación en Ciencias de la Alimentación (CIAL, CSIC-UAM), Madrid, Spain
| | - Vanessa Sánchez-Quezada
- Programa Doctorado en Ciencias de los Alimentos, Research and Graduate Studies in Food Science, School of Chemistry, Universidad Autónoma de Querétaro, Querétaro, México.
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18
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Wang M, He Q, Chen Z, Qin Y. Integrating multiomics analysis and machine learning to refine the molecular subtyping and prognostic analysis of stomach adenocarcinoma. Sci Rep 2025; 15:3843. [PMID: 39885324 PMCID: PMC11782604 DOI: 10.1038/s41598-025-87444-3] [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: 10/09/2024] [Accepted: 01/20/2025] [Indexed: 02/01/2025] Open
Abstract
Stomach adenocarcinoma (STAD) is a common malignancy with high heterogeneity and a lack of highly precise treatment options. We downloaded the multiomics data of STAD patients in The Cancer Genome Atlas (TCGA)-STAD cohort, which included mRNA, microRNA, long non-coding RNA, somatic mutation, and DNA methylation data, from the sxdyc website. We synthesized the multiomics data of patients with STAD using 10 clustering methods, construct a consensus machine learning-driven signature (CMLS)-related prognostic models by combining 10 machine learning methods, and evaluated the prognosis models using the C-index. The prognostic relationship between CMLS and STAD was assessed using Kaplan-Meier curves, and the independent prognostic value of CMLS was determined by univariate and multivariate regression analyses. we also evaluated the immune characteristics, immunotherapy response, and drug sensitivity of different CMLS groups. The results of the multiomics analysis classified STAD into three subtypes, with CS1 resulting in the best survival outcome. In total, 10 hub genes (CES3, AHCYL2, APOD, EFEMP1, CYP1B1, ASPN, CPE, CLIP3, MAP1B, and DKK1) were screened and constructed the CMLS was significantly correlated with prognosis in patients with STAD and was an independent prognostic factor for patients with STAD. Using the CMLS risk score, all patients were divided into a high CMLS group and a low CMLS group. Patients in the low-CMLS group had better survival, more enriched immune cells, and higher tumor mutation load scores, suggesting better immunotherapy responsiveness and a possible "hot tumor" phenotype. Patients in the high-CMLS group had a significantly poorer prognosis and were less sensitive to immunotherapy but were likely to benefit more from chemotherapy and targeted therapy. In this study, 10 clustering methods and 10 machine learning methods were combined to analyze the multiomics of STAD, classify STAD into three subtypes, and constructed CMLS-related prognostic model features, which are important for accurate management and effective treatment of STAD.
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Affiliation(s)
- Miaodong Wang
- Department of Traditional Chinese Medicine, Jinhua Central Hospital, Jinhua, 321000, Zhejiang, People's Republic of China
| | - Qin He
- Department of Traditional Chinese Medicine, Jinhua Central Hospital, Jinhua, 321000, Zhejiang, People's Republic of China
| | - Zeshan Chen
- Department of Traditional Chinese Medicine, People's Hospital of Guangxi Zhuang Autonomous Region, 6 Taoyuan Road, Qingxiu District, Nanning City, Guangxi Zhuang Autonomous Region, People's Republic of China.
| | - Yijue Qin
- Department of Traditional Chinese Medicine, People's Hospital of Guangxi Zhuang Autonomous Region, 6 Taoyuan Road, Qingxiu District, Nanning City, Guangxi Zhuang Autonomous Region, People's Republic of China
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Al Khzem AH, Shoaib TH, Mukhtar RM, Alturki MS, Gomaa MS, Hussein D, Tawfeeq N, Bano M, Sarafroz M, Alzahrani R, Alghamdi H, Rants’o TA. Repurposing FDA-Approved Agents to Develop a Prototype Helicobacter pylori Shikimate Kinase (HPSK) Inhibitor: A Computational Approach Using Virtual Screening, MM-GBSA Calculations, MD Simulations, and DFT Analysis. Pharmaceuticals (Basel) 2025; 18:174. [PMID: 40005988 PMCID: PMC11858459 DOI: 10.3390/ph18020174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 01/22/2025] [Accepted: 01/24/2025] [Indexed: 02/27/2025] Open
Abstract
Background/Objectives:Helicobacter pylori infects approximately half of the global population, causing chronic gastritis, peptic ulcers, and gastric cancer, a leading cause of cancer mortality. While current therapies face challenges from rising antibiotic resistance, particularly to clarithromycin, alongside treatment complexity and costs, the World Health Organization has prioritized the development of new antibiotics to combat this high-risk pathogen. In this study, we employed computer-aided drug design (CADD) methodologies, including molecular docking, Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) analysis, molecular dynamics (MD) simulations, and Density Functional Theory (DFT) calculations, to explore the potential repurposing of FDA-approved agents as inhibitors of Helicobacter pylori shikimate kinase (HpSK). Methods: Using the Glide module, the HTVS method was initially applied to screen 1615 FDA-approved agents followed by extra-precision (XP) docking for the obtained 111 hits. The obtained XP scores were used to confine the results to those hits with a score above the reference ligand, shikimate, score. This yielded 31 final hits with an XP score above -5.867. MM-GBSA calculations were performed on these top candidates and the reference ligand to refine the analysis and compounds' prioritization. Results: The 31 compounds displayed binding free energy (ΔGbind) values ranging from 3.61 to -55.92 kcal/mol, with shikimate exhibiting a ΔGbind of -34.24 kcal/mol and 10 hits having a lower ΔGbind value. Out of these ten, three drugs-Dolutegravir, Cangrelor, and Isavuconazonium-were selected for further analysis based on their drug-like properties. Robust and stable binding profiles for both Isavuconazonium and Cangrelor were verified via molecular dynamics simulation. Additionally, Density Functional Theory (DFT) analysis was conducted, and the Highest Occupied Molecular Orbitals (HOMOs), Lowest Unoccupied Molecular Orbitals (LUMOs), and the energy gap (HLG) between them were calculated. All three drug candidates displayed lower HLG values than shikimate, suggesting higher reactivity and more efficient electronic transitions than the reference ligand. Conclusions: These findings suggest that the identified drugs, although not optimal for direct repurposing, would serve as promising leads against Helicobacter pylori shikimate kinase. These drugs could be valuable leads for experimental assessment and further optimization, particularly with no prototype yet identified. In terms of potential for clinical repurposing, the results point to diflunisal as a promising candidate for further testing.
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Affiliation(s)
- Abdulaziz H. Al Khzem
- Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia; (M.S.G.); (N.T.); (M.B.); (M.S.)
| | - Tagyedeen H. Shoaib
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Gezira, Wad Madani 21111, Sudan; (T.H.S.); (R.M.M.)
| | - Rua M. Mukhtar
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Gezira, Wad Madani 21111, Sudan; (T.H.S.); (R.M.M.)
| | - Mansour S. Alturki
- Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia; (M.S.G.); (N.T.); (M.B.); (M.S.)
| | - Mohamed S. Gomaa
- Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia; (M.S.G.); (N.T.); (M.B.); (M.S.)
| | - Dania Hussein
- Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Khobar 31441, Saudi Arabia;
| | - Nada Tawfeeq
- Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia; (M.S.G.); (N.T.); (M.B.); (M.S.)
| | - Mohsina Bano
- Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia; (M.S.G.); (N.T.); (M.B.); (M.S.)
| | - Mohammad Sarafroz
- Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia; (M.S.G.); (N.T.); (M.B.); (M.S.)
| | - Raghad Alzahrani
- College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia; (R.A.); (H.A.)
| | - Hanin Alghamdi
- College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia; (R.A.); (H.A.)
| | - Thankhoe A. Rants’o
- Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT 84112, USA;
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20
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Salehi N, Alqamish M, Zarnegar R. Perioperative chemotherapy strategies in diffuse gastric cancer. World J Gastrointest Surg 2025; 17:101326. [PMID: 39872775 PMCID: PMC11757181 DOI: 10.4240/wjgs.v17.i1.101326] [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: 09/14/2024] [Revised: 11/22/2024] [Accepted: 12/02/2024] [Indexed: 12/27/2024] Open
Abstract
This study reviews the findings of a recent study by Li et al, which demonstrated that perioperative chemotherapy benefits patients with diffuse-type gastric cancer compared to surgery alone. Despite potential biases, the study supports the inclusion of perioperative chemotherapy in treatment guidelines. Neoadjuvant and adjuvant chemotherapy may also provide similar survival outcomes, allowing for flexible treatment planning.
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Affiliation(s)
- Niloufar Salehi
- Department of Surgery, Division of Endocrine & Minimally Invasive Surgery, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY 10128, United States
| | - Maria Alqamish
- Department of Surgery, Division of Endocrine & Minimally Invasive Surgery, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY 10128, United States
| | - Rasa Zarnegar
- Department of Surgery, Division of Endocrine & Minimally Invasive Surgery, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY 10128, United States
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21
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Najafi S, Mohammadkhah F, Salemi SA, Kamyab A, Jeihooni AK. The impact of educational intervention based on the theory of planned behavior on preventive behaviors for gastric cancer in obese and smoking individuals. BMC Cancer 2025; 25:129. [PMID: 39849396 PMCID: PMC11756175 DOI: 10.1186/s12885-025-13558-6] [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: 06/23/2024] [Accepted: 01/20/2025] [Indexed: 01/25/2025] Open
Abstract
BACKGROUND Gastric cancer remains a significant global health issue due to its aggressive nature and high heterogeneity, making early detection and prevention critical. Obesity and smoking are established risk factors that significantly contribute to the development of gastric cancer. Despite the clear links between these risk factors and the disease, there is a lack of targeted educational interventions that address these behaviors. This study aims to fill this gap by investigating the impact of an educational intervention based on the Theory of Planned Behavior (TPB) on promoting preventive behaviors for gastric cancer among obese and smoking individuals. METHODS This quasi-experimental study was conducted in 2021-2022 on 150 obese or overweight individuals, more than 25 years old who smoked (cigarettes and hookah) in Fasa city, Iran. From six urban health centers, two centers were randomly selected (one as the experimental group and the other as the control group). Data collection tools included a demographic characteristics questionnaire based on the TPB model (a researcher-made questionnaire). Based on pre-test results, the educational intervention for the experimental group included 12 educational sessions for 50 min, following the TPB model, through lectures, Question and Answers, group discussions, practical demonstrations, video clips, and PowerPoint presentations. The questionnaires were completed by both groups before and six months after the intervention. Data were analyzed using SPSS 22 and descriptive and analytical statistical methods (paired t- test, McNemar test, Chi-square test, and independent t-test) (p < 0.05). RESULTS The results showed no significant difference between the two groups before the educational intervention. However, six months after the intervention, the experimental group showed a significant increase in TPB model cues (awareness, attitude, subjective norms, perceived behavioral control, behavioral intention, and behavior) (P < 0.001). CONCLUSION The findings of the present study indicate that the educational intervention based on the TPB model is useful in improving gastric cancer screening and preventive behaviors. It can also be used in planning and implementing appropriate programs to prevent and treat this disease.
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Affiliation(s)
- Siamak Najafi
- Department of Internal Medicine, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Fatemeh Mohammadkhah
- Department of Community health, child nursing and aging, Ramsar School of Nursing, Babol University of Medical Sciences, Babol, Iran
| | - Saina Alempour Salemi
- Department of Public Health, School of Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amirhossein Kamyab
- Department of Community Medicine, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Ali Khani Jeihooni
- Nutrition Research Center, Department of Public Health, School of Health, Shiraz University of Medical Sciences, Shiraz, Iran.
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22
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Lamberti G, Campana D. Reply to 'The need for a better classification system for gastric neoplasms'. Nat Rev Dis Primers 2025; 11:7. [PMID: 39848965 DOI: 10.1038/s41572-024-00591-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2025]
Affiliation(s)
- Giuseppe Lamberti
- Department of Medical and Surgical Sciences, Alma Mater Studiorum - Universtà di Bologna, Bologna, Italy
| | - Davide Campana
- Department of Medical and Surgical Sciences, Alma Mater Studiorum - Universtà di Bologna, Bologna, Italy.
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23
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Chen Z, Yu T, Wang Y, Li J, Zhang B, Zhou L. Mechanistic insights into the role of traditional Chinese medicine in treating gastric cancer. Front Oncol 2025; 14:1443686. [PMID: 39906672 PMCID: PMC11790455 DOI: 10.3389/fonc.2024.1443686] [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: 06/04/2024] [Accepted: 12/30/2024] [Indexed: 02/06/2025] Open
Abstract
Gastric cancer remains a leading cause of cancer-related mortality worldwide, with advanced stages presenting significant challenges due to metastasis and drug resistance. Traditional Chinese Medicine (TCM) offers a promising complementary approach characterized by holistic treatment principles and minimal side effects. This review comprehensively explores the multifaceted mechanisms by which TCM addresses gastric cancer. Specifically, we detail how TCM inhibits aerobic glycolysis by downregulating key glycolytic enzymes and metabolic pathways, thereby reducing the energy supply essential for cancer cell proliferation. We examine how TCM suppresses angiogenesis by targeting the vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) pathways, effectively starving tumors of nutrients and oxygen required for growth and metastasis. Furthermore, TCM modulates the immune microenvironment by enhancing the activity of effector immune cells such as CD4+ and CD8+ T cells and natural killer (NK) cells while reducing immunosuppressive cells like regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). These actions collectively contribute to slowing tumor progression, inhibiting metastasis, and enhancing the body's antitumor response. The insights presented underscore the significant potential of TCM as an integral component of comprehensive gastric cancer treatment strategies, highlighting avenues for future research and clinical application to improve patient outcomes.
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Affiliation(s)
- Ziqiang Chen
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, China
| | - Ting Yu
- Department of Rheumatism, Third Affiliated Clinical Hospital to Changchun University of Chinese Medicine, Changchun, Jilin, China
| | - Yunhe Wang
- Department of Endocrinology, Metabolism and Gastroenterology, Third Affiliated Clinical Hospital to Changchun University of Chinese Medicine, Changchun, Jilin, China
| | - Jiaxin Li
- Changchun University of Chinese Medicine, Changchun, Jilin, China
| | - Bo Zhang
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, China
| | - Liya Zhou
- Changchun University of Chinese Medicine, Changchun, Jilin, China
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24
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Holzer CS, Pukaluk A, Viertler C, Regitnig P, Charry EM, Wolinski H, Eschbach M, Caulk AW, Holzapfel GA. Implications of compressive loading of the stomach wall: Interplay between mechanical deformation and microstructure. Acta Biomater 2025; 192:101-118. [PMID: 39694163 DOI: 10.1016/j.actbio.2024.12.023] [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: 06/30/2024] [Revised: 12/06/2024] [Accepted: 12/10/2024] [Indexed: 12/20/2024]
Abstract
During gastric surgery, the stomach wall is compressed with clamps and sutures or staple lines. These short- and long-term deformations can severely compromise the integrity of the tissue and make it difficult for the stomach wall to respond and remodel to the new loading conditions. Consequently, serious intra- and postoperative complications such as the formation of leaks during bariatric surgeries, can be associated with these immense tissue deformations. Hence, the study aimed to investigate the effects of compressive loading of the stomach wall in the radial direction. This was done by macroscopic mechanical loading of the stomach wall in each region of the stomach and evaluating the microstructural changes inflicted in the tissue. For this purpose, several imaging techniques were used, i.e., a histological analysis, second-harmonic generation microscopy, and X-ray micro-computed tomography. The combination of these three methods allowed us to investigate the gradual compression of the different stomach layers as well as the local reorientation and deformation of the main microstructural components, e.g., collagen fibers and muscle bundles. Importantly, this study found that the collagen bundles in the stomach wall straighten and reorient toward the circumferential-longitudinal plane and partially fan out with increased radial compressive deformation. The 3D scans of the stomach wall indicated a deterioration of the blood vessels and buckling of the mucosal glands due to compression. Statement of significance Unfortunately, little is known about the load transfer in the stomach wall during gastric surgery and the associated deformations on the macro- and microscale. The present study investigates the structural changes of the stomach wall, its layers and the inherent biological building blocks using histology, multi-photon microscopy, and micro-computed tomography. For the first time, the layer-specific response to stepwise radial compression of the stomach wall was studied, the related collagen fiber parameters were estimated, and a 3D sample structure was visualized. This clinically-oriented study links the structural changes within the wall to the postoperative remodel- ing process and the irreversibly altered gastric motility, thereby underscoring its relevance to the field of biomedical engineering, e.g., the development and improvement of surgical instruments.
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Affiliation(s)
| | - Anna Pukaluk
- Institute of Biomechanics, Graz University of Technology, Austria
| | - Christian Viertler
- Diagnostic and Research Institute of Pathology, Medical University of Graz, Austria
| | - Peter Regitnig
- Diagnostic and Research Institute of Pathology, Medical University of Graz, Austria
| | | | - Heimo Wolinski
- Institute of Molecular Biosciences, University of Graz, Austria; Field of Excellence BioHealth - University of Graz, Austria
| | | | | | - Gerhard A Holzapfel
- Institute of Biomechanics, Graz University of Technology, Austria; Department of Structural Engineering, NTNU, Norway.
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25
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Yang C, Rodriguez y Baena A, Manso BA, Hu S, Lopez-Magaña R, Ohanyan M, Ottemann KM. Helicobacter pylori luxS mutants cause hyperinflammatory responses during chronic infection. Microbiol Spectr 2025; 13:e0107324. [PMID: 39641542 PMCID: PMC11705807 DOI: 10.1128/spectrum.01073-24] [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: 04/28/2024] [Accepted: 08/30/2024] [Indexed: 12/07/2024] Open
Abstract
Helicobacter pylori infects roughly half the world's population, causing gastritis, peptic ulcers, and gastric cancer in a subset. These pathologies occur in response to a chronic inflammatory state, but it is not fully understood how H. pylori controls this process. We characterized the inflammatory response of H. pylori mutants that cannot produce the quorum sensing molecule autoinducer 2 (AI-2) by deleting the gene for the AI-2 synthase, luxS. Our work shows that H. pylori luxS mutants colonize the stomach normally but recruit high numbers of CD4+ T cells to the stomach during chronic infection. This increase in the number of CD4+ T cells correlated with elevated expression of CXCL9, a chemokine important for T cell recruitment. Together, our results suggest that H. pylori may utilize AI-2 signaling to modulate the inflammatory response during chronic infection. IMPORTANCE Many bacteria signal to each other using quorum sensing signals. One type of signal is called autoinducer 2 (AI-2), which is produced and sensed by the LuxS enzyme found in many bacteria, including the gastric pathogen Helicobacter pylori. H. pylori establishes chronic infections that last for decades and lead to serious disease outcomes. How AI-2 signaling and LuxS contribute to chronic H. pylori infection has not been studied. In this work, we analyzed how loss of H. pylori-created AI-2, via mutation of luxS, affects H. pylori chronic infection. luxS mutants did not have significant colonization defects, similar to their reported phenotype during early infection, but they did have high stomach levels of effector and regulatory T cells and T-cell-recruiting chemokines. These results suggest that H. pylori LuxS may play more of a role in modulating the immune response versus colonization.
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Affiliation(s)
- Christina Yang
- Department of Microbiology and Environmental Toxicology, University of California Santa Cruz, Santa Cruz, California, USA
| | | | - Bryce A. Manso
- Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, USA
| | - Shuai Hu
- Department of Microbiology and Environmental Toxicology, University of California Santa Cruz, Santa Cruz, California, USA
| | - Raymondo Lopez-Magaña
- Department of Microbiology and Environmental Toxicology, University of California Santa Cruz, Santa Cruz, California, USA
| | - Mané Ohanyan
- Department of Microbiology and Environmental Toxicology, University of California Santa Cruz, Santa Cruz, California, USA
| | - Karen M. Ottemann
- Department of Microbiology and Environmental Toxicology, University of California Santa Cruz, Santa Cruz, California, USA
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26
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Liu Y, Du F, Chen B, Rastogi S, Huang Y. A meta-analysis of randomized controlled trials examining the efficacy and safety of elemene in combination with chemotherapy for the treatment of gastric cancer. Explore (NY) 2025; 21:103076. [PMID: 39626582 DOI: 10.1016/j.explore.2024.103076] [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: 06/07/2024] [Revised: 10/18/2024] [Accepted: 11/03/2024] [Indexed: 01/22/2025]
Abstract
BACKGROUND Elemene is a naturally occurring chemical derived from plants of the Zingiberaceae family, and it finds application in several cancer-related contexts. Nevertheless, there is a dearth of comprehensive assessment about the combined effectiveness and safety of chemotherapy in gastric cancer (GC). OBJECTIVE To investigate the safety and effectiveness of elemene in conjunction with chemotherapy for the treatment of Gastric cancer. METHODS A comprehensive search of Medline, EMBASE, Scopus, and Cochrane Library identified peer-reviewed journal papers. OR and RR were calculated, along with their 95 % confidence ranges. We assessed heterogeneity using Cochrane Q and I2 statistics and the relevant P-value. The analysis used RevMan 5.3. RESULTS Current meta-analysis includes 11 RCTs with 726 GC patients, 364 of whom received elemene paired with treatment and 362 received standard chemotherapy. Elemene-coated chemotherapy improves ORR (RR 1.43, 95 % CI 1.22-1.67, p < 0.00001), reduces blood system toxicity (OR 0.49, 95 % CI 0.35-0.69, p < 0.0001), nausea and vomiting (RR 0.65, 95 % CI 0.55-0.77), diarrhea (RR 0.73, 95 % CI 0.58-0.90), and liver problems (RR 0.64, 95 % CI 0.49-0.83).Subgroup analysis showed that both oral and intravenous administration improved ORR statistically, and a network diagram with consistent connectivity, well-defined network architecture, and high-quality evidence shows that elemene combined with chemotherapy has significant therapeutic efficacy. CONCLUSION Elemene may possess the capacity to enhance the effectiveness and mitigate the adverse effects of gastric cancer chemotherapy. Nevertheless, due to the restricted number of studies incorporated, additional research studies utilizing sizable samples are required to validate the aforementioned findings.
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Affiliation(s)
- Yige Liu
- Department of Gastroenterology, Shanghai Construction Group (SCG) Hospital, Shanghai 200000, China.
| | - Feng Du
- Department of General Surgery, Ezhou Central Hospital, Ezhou Hubei 436000, China.
| | - Bo Chen
- Department of Oncology, Chengdu First People's Hospital, Chengdu Sichuan 610041, China.
| | - Sanjay Rastogi
- Gastroenterology Oncology, Boston University, MA 02111 USA.
| | - Yanhua Huang
- Department of Gastroenterology, Nantong Haimen People's Hospital, Nantong Jiangsu 226100, China.
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Zhang J, Zhu W, Yang S, Liu J, Tang F, Li Y. Identification and Validation of a Novel Prognostic Signature of Gastric Cancer Based on Seven Complement System-Related Genes: An Integrated Analysis. Crit Rev Eukaryot Gene Expr 2025; 35:1-22. [PMID: 39964966 DOI: 10.1615/critreveukaryotgeneexpr.2024057000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/20/2025]
Abstract
The complement system (CS) is linked to the progression of gastric cancer (GC), which has a high mortality rate, though its mechanisms in GC remain unclear. This study aims to identify CS-related prognostic genes with causal links to GC, and to investigate their mechanisms. The intersection between differentially expressed genes (DEGs) obtained from the TCGA-STAD dataset and CS-related genes (CRGs) was defined as differentially expressed CRGs (DCRGs). Prognostic genes with a causal association with GC (pCDCRGs) were sequentially identified via Mendelian randomization (MR) analysis and Cox and least absolute shrinkage and selection operator (LASSO) regression analyses, followed by expression analysis. A gene signature and a nomogram were then established based on pCDCRGs and independent prognostic factors. Subsequent analyses focused on functional enrichment, immune relevance, drug sensitivity, gene interactions, and molecular regulatory networks. Eventually, reverse transcription-quantitative PCR (RT-qPCR) was employed to validate expression of pCDCRGs. DCRGs were obtained from the intersection of 8,418 DEGs and 241 CRGs. Among 12 DCRGs with causal association (CDCRGs) with GC, 7 genes were identified as pCDCRGs, including FANCG, FANCF, F2R, C4BPA, SERPINF2, PROC, and CD59. Notably, CD59 was markedly highly expressed in the normal group, whereas the other genes were markedly highly expressed in the GC group. Afterward, an accurate pCDCRG signature was developed. Risk score, age, and stage were recognized as independent risk factors, and the constructed nomogram demonstrated strong predictive accuracy. Additionally, analyses indicated that these 7 pCDCRGs may influence GC by affecting pathways such as complement and coagulation cascades, immune cell infiltration, immune characteristics, immunotherapy responses, and drug sensitivity. These effects may be linked to gene interactions and the regulatory roles of lncRNAs like RMRP and miRNAs such as hsa-mir-613. RT-qPCR showed C4BPA, PROC, F2R, and SERPINF2 were markedly up-regulated, whereas CD59 was markedly down-regulated in GC tissues. This study identified seven complement system-related prognostic genes with causal links to GC, based on which we developed a highly predictive 7-pCDCRG signature, providing valuable insights for clinical prognostic prediction and immunotherapy in GC patients.
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Affiliation(s)
- Jiaxing Zhang
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, Gansu Province, China; Digestive System Tumor Prevention and Treatment and Translational Medicine Engineering Innovation Center of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Weijing Zhu
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, Gansu Province, China; Digestive System Tumor Prevention and Treatment and Translational Medicine Engineering Innovation Center of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Shengrui Yang
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, Gansu Province, China; Digestive System Tumor Prevention and Treatment and Translational Medicine Engineering Innovation Center of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Jie Liu
- Ecosystem Change and Population Health Research Group, School of Public Health and Social Work, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059, Australia
| | - Futian Tang
- Digestive System Tumor Prevention and Treatment and Translational Medicine Engineering Innovation Center of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Yumin Li
- The Second Hospital & Clinical Medical School, Lanzhou University
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28
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Pan Y, Ma Y, Guan H, Dai G. Pre-treatment of hyponatremia as a biomarker for poor immune prognosis in advanced or metastatic gastric cancer: A retrospective case analysis. Hum Vaccin Immunother 2024; 20:2414546. [PMID: 39411929 PMCID: PMC11486141 DOI: 10.1080/21645515.2024.2414546] [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: 05/17/2024] [Revised: 09/22/2024] [Accepted: 10/07/2024] [Indexed: 10/19/2024] Open
Abstract
Hyponatremia, a prevalent electrolyte imbalance among tumor patients, has often been overlooked regarding its prognostic significance for immunotherapy. In this study, we delved into the prognostic ramifications of hyponatremia in advanced gastric cancer (AGC) patients undergoing immunotherapy. Enrolling AGC patients diagnosed between December 2014 and May 2021, we extracted pertinent data from electronic medical records, with a median follow-up of 35.8 months. Kaplan-Meier curves illuminated patients' progression-free survival (PFS) and overall survival (OS), while survival disparities were tested using the Mantel-Haenszel log rank test. COX and logistic regressions were employed to scrutinize the correlation between serum sodium levels and prognosis in 268 AGC patients, both at baseline and during treatment. Notably, patients with hyponatremia exhibited shorter PFS (4.7 vs 2.1 months, p = .001*) and OS (12.5 vs 3.9 months, p < .001*). Serum sodium emerged as an independent prognostic factor for both PFS (HR = 1.773; 95% CI 1.067-2.945; p = .001*) and OS (HR = 1.773; 95% CI 1.067-2.945; p = .003*). Subgroup analysis revealed that AGC patients with hyponatremia derived no benefit from immunotherapy in terms of PFS and OS. Strikingly, a decrease in serum sodium during immunotherapy was associated with early relapse and mortality. Based on these findings, we hypothesize that hyponatremia portends poor prognostic outcomes in AGC patients treated with immunotherapy and may serve as a valuable prognostic biomarker. However, further large-scale prospective studies are warranted to validate these observations.
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Affiliation(s)
- Yuting Pan
- Department of Medical Oncology, Medical School of Chinese PLA, Beijing, China
- Department of Medical Oncology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Yue Ma
- Department of Medical Oncology, Medical School of Chinese PLA, Beijing, China
- Department of Medical Oncology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Huafang Guan
- External Relations Office, Yingtan City People’s Hospital, Yingtan, China
| | - Guanghai Dai
- Department of Medical Oncology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
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Elgenidy A, Alomari O, Hesn MM, Khaled A, Nada SA, Elsayed M, Mahmoud A, Al-kurdi MAM, Afifi AM, Cholankeril G. Relative Survival, Conditional Survival, and Causes of Death in Patients with Early Gastric Cancer, with a Focus on Differences Between Cardia and Non-Cardia Cancer. Cancers (Basel) 2024; 16:4262. [PMID: 39766160 PMCID: PMC11674421 DOI: 10.3390/cancers16244262] [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: 11/05/2024] [Revised: 12/11/2024] [Accepted: 12/19/2024] [Indexed: 01/11/2025] Open
Abstract
Background: Many researchers believe that cardia (CGC) and non-cardia (NCGC) are two different types of tumors, having different features like incidence rate, risk factors, geographical location, and socioeconomic status. This study aims to investigate the causes of death (COD) survival rates among early gastric cancer patients with a focus on differences between CGC and NCGC. Methods: This retrospective study employed SEER*stat software (version 8.3.92) to analyze the SEER 17 plus dataset (2000-2019). Standardized mortality ratios (SMR) were computed. Relative survival and conditional survival post-diagnosis were calculated using R software (version 4.1.0) among the different subgroups. Results: Within the follow-up period, 55.4% (5381) died, predominantly within the initial year post-diagnosis. Esophageal cancer was the leading non-gastric cancer cause in CGC, while miscellaneous tumors dominated in NCGC. The 1-year and 5-year relative survival for CGC patients were 76.4% and 48.9% respectively, while for NCGC were 80.4% and 63.9%. The 3-year conditional survival after 1 year and 5e years of survival for CGC were 68.7% and 88.8%, respectively, while for NCGC were 82.2% and 93.5%, respectively. This means that the longer a person has survived after diagnosis with cancer, the greater the likelihood that person will survive for another 3 years. Conclusions: This study sheds light on the substantial impact of non-cancer COD in GC patients, underscoring the necessity of considering comorbidities in their comprehensive management and follow-up. Impact: This study contributes valuable insights for clinical decision-making and informs future research directions regarding CGC and NCGC.
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Affiliation(s)
- Anas Elgenidy
- Department of Neurology, Cairo University, Cairo 11652, Egypt;
| | - Omar Alomari
- Hamidiye International School of Medicine, University of Health Sciences, 34668 Istanbul, Turkey;
| | - Mohamed Marey Hesn
- Damietta Faculty of Medicine, Al-Azhar University, Damietta 34517, Egypt; (M.M.H.); (A.K.)
| | - Anas Khaled
- Damietta Faculty of Medicine, Al-Azhar University, Damietta 34517, Egypt; (M.M.H.); (A.K.)
| | - Sarah A. Nada
- Faculty of Medicine, Menofia University, Shebin El-Kom 32861, Egypt;
| | - Mostafa Elsayed
- Faculty of Medicine, Zagazig University, Zagazig 44691, Egypt;
| | - Ali Mahmoud
- College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43614, USA;
| | | | - Ahmed M. Afifi
- University of Toledo Medical Center, Toledo, OH 43614, USA
| | - George Cholankeril
- Section of Gastroenterology and Hepatology, Margaret M. and Albert B. Alkek Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA;
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Kossenas K, Moutzouri O, Georgopoulos F. Robotic vs laparoscopic distal gastrectomy with Billroth I and II reconstruction: a systematic review and meta-analysis. J Robot Surg 2024; 19:30. [PMID: 39699804 DOI: 10.1007/s11701-024-02193-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 12/11/2024] [Indexed: 12/20/2024]
Abstract
Robotic distal gastrectomy (RDG) has been increasingly used for the treatment of gastric cancer, however, its comparative safety and efficacy against the laparoscopic approach (LDG), remains unclear, especially when accounting the reconstruction method as a confounder. This systematic review and meta-analysis aims to evaluate the short-term outcomes of RDG vs LDG In patIents with gastric cancer, undergoing Billroth I and II reconstruction. A systematic review was conducted in accordance with PRISMA guidelines. We searched Pubmed, Scopus and the Cochrane Library, up to October 22nd, 2024. The primary outcomes analyzed were the blood loss, operative duration, and the number of harvested lymph nodes and the secondary outcomes included overall complications, time to oral intake, duration of hospitalization and time to first flatus. Random-effects models were used to calculate weighted mean differences (WMD) and Odds ratios (OR) with 95% confidence intervals (CI), and heterogeneity was assessed using the I2 statistic. P values were also calculated. Sensitivity analysis was performed for outcomes with moderate to high heterogeneity. Five studies were included, involving 811 patients (RDG: n = 289, LDG: n = 522). RDG was associated with a significantly longer operative duration compared to LDG (WMD = 34.14 min, 95%CI 10.92 to 57.35, P = 0.004, I2 = 91%). RDG patients initiated oral intake earlier (WMD = -0.20 days, 95%CI -0.39 to -0.01, P = 0.03, I2 = 45%). RDG resulted in shorter hospital stays (WMD = -1.48 days, 95%CI -2.91 to -0.04, P = 0.04, I2 = 86%). RDG patients had a faster return to bowel function (time to first flatus) (WMD = -0.33 days, 95%CI -0.50 to -0.15, P = 0.00003, I2 = 57%). No statistically significant differences were observed regarding blood loss between RDG and LDG (WMD = -3.88 mL, 95%CI -21.63 to 13.87, P = 0.67, I2 = 78%). There was no statistically significant difference in complication rates (OR = 0.61, 95%CI 0.36 to 1.03, P = 0.06, I2 = 0%). No significant differences were observed regarding the number of lymph nodes harvested (WMD = -0.49, 95%CI -3.02 to 2.04, P = 0.70, I2 = 24%). Sensitivity analysis confirmed the robustness of the findings of operative duration and time to first flatus. RDG with BI/ BII requires longer operative duration, but it associated with faster recovery compared to LDG. No differences were observed between RDG and LDG with regards to overall complications, number of harvested lymph nodes and blood loss, showing that RDG is as safe and oncological equivalent to LDG. Future studies particularly, multi-center randomized clinical trials, should have a longer follow up period and examine the type of reconstruction separately. PROSPERO registration: CRD42024605895.
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Affiliation(s)
- Konstantinos Kossenas
- Department of Basic and Clinical Sciences, University of Nicosia Medical School, 21 Ilia Papakyriakou, 2414 Engomi, P.O. Box 24005, 1700, Nicosia, Cyprus.
| | - Olga Moutzouri
- Department of Basic and Clinical Sciences, University of Nicosia Medical School, 21 Ilia Papakyriakou, 2414 Engomi, P.O. Box 24005, 1700, Nicosia, Cyprus
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Ofluoğlu CB, Aydın IC, Mülküt F, Uzun O, Senger AS, Gülmez S, Duman U, Polat E, Duman M. Diagnostic Efficacy of Staging Laparoscopy Compared to CT and PET-CT in Gastric Cancer: A Retrospective Cohort Analysis. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:2079. [PMID: 39768958 PMCID: PMC11677282 DOI: 10.3390/medicina60122079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 12/09/2024] [Accepted: 12/17/2024] [Indexed: 01/11/2025]
Abstract
Background and Objectives: This study aimed to assess the diagnostic accuracy and prognostic significance of staging laparoscopy (SL) compared to computed tomography (CT) and positron emission tomography-computed tomography (PET-CT) in gastric cancer staging. We evaluated the ability of SL to detect occult peritoneal metastases and influence of SL on survival outcomes across cancer stages and treatment approaches. Materials and Methods: In this retrospective cohort study, 95 patients with gastric cancer underwent preoperative assessment using CT, PET-CT, and SL between 2018 and 2024. Diagnostic performance metrics were calculated for SL, CT, and PET/CT across the local, locally advanced, and metastatic stages. Survival outcomes were analyzed using Kaplan-Meier curves, and comparisons were made using log-rank tests. A multivariable Cox proportional hazards model incorporating interaction terms was used to determine the independent prognostic factors affecting survival, focusing on SL findings and cytology results. Results: The cohort comprised 75 males (78.9%) and 20 females (21.1%), with a mean age of 57.4 ± 10.1 years. The tumor location distribution was predominant in the corpus (31.1%) and cardia. Tumor staging revealed that 48.1% were classified as T3 and 28.8% as T4, respectively. Diagnostic accuracy analysis showed that SL outperformed CT and PET-CT in detecting peritoneal metastasis across all stages. Specifically, SL demonstrated a sensitivity and specificity of 85% and 95% for local disease, 92% and 80% for locally advanced disease, and 95% and 99% for metastatic disease, significantly exceeding those of CT and PET-CT. Patients with SL findings had a median overall survival (OS) of 30 months compared with 20 months for those assessed only with CT and PET-CT (p < 0.05). The stage-specific median OS for SL patients was 40 months in the local, 25 months in the locally advanced (p < 0.05), and 15 months in the metastatic disease (p < 0.01) groups, indicating significant survival benefits. Multivariable Cox regression identified SL findings as an independent factor associated with reduced mortality risk (HR: 0.70, 95% CI: 0.50-0.90, p < 0.01), while positive cytology findings predicted poorer survival (HR: 1.80, 95% CI: 1.25-2.60, p < 0.01). Interaction terms revealed that SL yielded greater survival benefits in patients with metastatic disease (hazard ratio [HR]: 0.60, p < 0.01) and those undergoing systemic therapy (HR: 0.75, p = 0.04). Conclusions: SL provides superior diagnostic accuracy and prognostic information for advanced gastric cancer staging compared with CT and PET-CT. By accurately detecting peritoneal metastasis, SL aids in optimizing treatment plans, particularly in advanced stages, thus potentially improving patient outcomes.
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Affiliation(s)
- Cem Batuhan Ofluoğlu
- Department of Gastroenterology Surgery, Sancaktepe Sehit Prof. Dr. İlhan Varank Training and Research Hospital, University of Health Sciences, 34147 Istanbul, Turkey
| | - Isa Caner Aydın
- Gastroenterology Surgery Clınıc, Zonguldak Atatürk State Hospital, Health Mınıstry of Turkısh Republıc, 34147 Zonguldak, Turkey;
| | - Fırat Mülküt
- Department of General Surgery, Sancaktepe Sehit Prof. Dr. İlhan Varank Training and Research Hospital, University of Health Sciences, 34147 Istanbul, Turkey;
| | - Orhan Uzun
- Gastroenterology Surgery Clınıc, Koşuyolu Hıgh Specıalızatıon Educatıon and Research Hospıtal, University of Health Sciences, 34147 Istanbul, Turkey; (O.U.); (A.S.S.); (S.G.); (E.P.); (M.D.)
| | - Aziz Serkan Senger
- Gastroenterology Surgery Clınıc, Koşuyolu Hıgh Specıalızatıon Educatıon and Research Hospıtal, University of Health Sciences, 34147 Istanbul, Turkey; (O.U.); (A.S.S.); (S.G.); (E.P.); (M.D.)
| | - Selçuk Gülmez
- Gastroenterology Surgery Clınıc, Koşuyolu Hıgh Specıalızatıon Educatıon and Research Hospıtal, University of Health Sciences, 34147 Istanbul, Turkey; (O.U.); (A.S.S.); (S.G.); (E.P.); (M.D.)
| | - Uğur Duman
- General Surgery Clınıc, Bursa Yüksek İhtisas Training and Research Hospital, University of Health Sciences, Bursa Provincial Health Directorate, 16290 Bursa, Turkey;
| | - Erdal Polat
- Gastroenterology Surgery Clınıc, Koşuyolu Hıgh Specıalızatıon Educatıon and Research Hospıtal, University of Health Sciences, 34147 Istanbul, Turkey; (O.U.); (A.S.S.); (S.G.); (E.P.); (M.D.)
| | - Mustafa Duman
- Gastroenterology Surgery Clınıc, Koşuyolu Hıgh Specıalızatıon Educatıon and Research Hospıtal, University of Health Sciences, 34147 Istanbul, Turkey; (O.U.); (A.S.S.); (S.G.); (E.P.); (M.D.)
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Maharjan U, Kauppila JH. University hospital status and gastric cancer mortality: A population-based nationwide study in Finland. J Gastrointest Surg 2024:101932. [PMID: 39701514 DOI: 10.1016/j.gassur.2024.101932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 11/23/2024] [Accepted: 12/14/2024] [Indexed: 12/21/2024]
Abstract
BACKGROUND Gastric cancer remains a significant global health issue with increasing mortality, despite advancements in treatment. Previous studies have suggested that surgery performed at university hospitals may influence surgical outcomes and mortality rates, but evidence of its effect on gastric cancer remains limited. This study aimed to investigate whether gastrectomy performed at university hospitals reduces short-term and long-term mortality rates in Finland. METHODS This nationwide population-based retrospective cohort study analyzed patients with gastric cancer who underwent gastrectomy in Finland from 1987 to 2016, using data from the Finnish Cancer Registry, Finnish Patient Registry, and Finnish Death Registry. The study compared 5-year, 30-day, and 90-day all-cause mortality rates between patients treated at university hospitals and those treated at nonuniversity hospitals, with adjustments for confounders using multivariate Cox regression models. RESULTS Of 10,455 patients who underwent gastrectomy in Finland between 1987 and 2016, most were treated in nonuniversity hospitals. Patients who underwent gastrectomy at university hospitals were generally younger and had more comorbidities and more advanced cancer stages. Of note, 30-day, 90-day, and 5-year survival rates were higher in university hospitals than in nonuniversity hospitals, although the differences in 90-day and 5-year survival rates were not statistically significant in more recent years. CONCLUSION Our findings suggest that gastrectomy performed at university hospitals in Finland is associated with lower short-term and long-term mortality rates than gastrectomy performed at nonuniversity hospitals. In addition, our findings support the potential benefits of centralizing gastric cancer surgical procedures at university hospitals. However, further research is needed to explore the underlying reasons.
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Affiliation(s)
- Urgena Maharjan
- Surgery Research Unit, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland.
| | - Joonas H Kauppila
- Surgery Research Unit, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland; Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
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Zhang H, Tang X, Zhang J, Jiang D, Gong D, Fan Y. Association between weight loss and survival outcomes in patients with gastric cancer: a meta-analysis. Eur J Cancer Prev 2024:00008469-990000000-00197. [PMID: 39718216 DOI: 10.1097/cej.0000000000000946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2024]
Abstract
Patients with gastric cancer often experience weight loss. A meta-analysis was conducted to evaluate the association between weight loss and survival outcomes in gastric cancer patients. We searched PubMed, Embase, and Web of Science according to the PECOS criteria: population (gastric cancer patients), exposure (weight loss), comparator (weight stable), outcomes [overall survival (OS) or recurrence-free survival], and study design (cohort studies). The prognostic value was expressed by combing the fully adjusted hazard ratio with 95% confidence interval (CI) for weight loss versus stable weight. Eighteen studies reporting on 16 articles involving 26 080 patients were identified. The pooled adjusted relative risk showed that weight loss was associated with shorter OS (hazard ratio 1.48; 95% CI: 1.32-1.66; I2 = 71.0%) and recurrence-free survival (hazard ratio 1.59; 95% CI: 1.17-2.16; I2 = 52.0%). The pooled adjusted hazard ratio of OS was 1.39 (95% CI: 1.14-1.70; I2 = 74.6%) among the studies that defined weight loss meeting the criteria for cancer cachexia. Moreover, stratified analysis revealed that weight loss significantly predicted OS, irrespective of patients' age, study design, tumor stage, timing of sampling weight loss, or follow-up duration. Weight loss significantly predicts OS and recurrence-free survival in gastric cancer patients. Monitoring weight changes can improve risk classification of gastric cancer, particularly in those with advanced disease.
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Affiliation(s)
- Heng Zhang
- Department of General Surgery, Nanjing Lishui District People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing
| | - Xuan Tang
- Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang
| | - Junfang Zhang
- Department of Medical Nutrition, Nanjing Lishui District People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, China
| | - Dapeng Jiang
- Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang
| | - Dandan Gong
- Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang
| | - Yu Fan
- Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang
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Luo D, Xu H, Jiang C, Zheng J, Wu D, Tou L, Que H, Sun Z. Knowledge, attitudes, and practices of primary caregivers of gastric cancer patients regarding postoperative dietary management. BMC Cancer 2024; 24:1487. [PMID: 39627744 PMCID: PMC11613799 DOI: 10.1186/s12885-024-13240-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 11/25/2024] [Indexed: 12/08/2024] Open
Abstract
BACKGROUND Family caregivers of gastric cancer (GC) patients after gastrectomy have a strong demand for nutrition knowledge. This study investigates the knowledge, attitudes, and practices (KAP) of primary caregivers of GC patients regarding postoperative dietary management. METHODS We conducted a cross-sectional study, collecting data through questionnaire distribution. Demographic information of the respondents and KAP scores were assessed and analyzed. RESULTS Of 508 included participants, majority were female (59.84%) urban residents (78.94%), aged 40-60 years (53.15%). Caretakers were primarily spouses of GC patient (50.39%) or parents (10.43%), only child (12.99%) or non-only child (24.21%). Notable percentage of poor knowledge and practice was found among participants (45.05% and 40.55%, respectively), while attitude was predominantly positive (99.41%). Correlation analysis revealed a weak positive correlation between knowledge and attitude scores (r = 0.150, P < 0.001) and negative link to practice scores (r=-0.228, P < 0.001); attitude scores were positively correlated with practice (r = 0.117, P = 0.008). Multivariate logistic regression analysis found that higher attitude scores were independently associated with higher practice scores (OR = 1.360; 95%CI, 1.223-1.513), P < 0.001), while higher knowledge scores (OR = 0.684; 95%CI, 0.575-0.815), P < 0.001), older age (OR = 0.951; 95%CI, 0.918-0.985), P = 0.005), duration of caregiving > 3 months (3-6 months (OR = 0.415; 95%CI, 0.193-0.894, P = 0.025); 6 months-1 year (OR = 0.269; 95%CI, 0.120-0.606), P = 0.002); >1 year (OR = 0.290; 95%CI, 0.120-0.705), P = 0.006), and follow-up location after patient's surgery (OR = 0.072 (0.033-0.160), P < 0.001) were independently associated with lower practice scores. CONCLUSIONS Family caregivers of GC patients that participated in this study demonstrated moderate knowledge and practice, but positive attitude towards dietary management after gastrectomy.
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Affiliation(s)
- Desheng Luo
- Department of Gastrointestinal Abdominal Hernia Surgery, Lishui Municipal Central Hospital, Lishui, Zhejiang, 323000, China.
| | - Hongtao Xu
- Department of Gastrointestinal Abdominal Hernia Surgery, Lishui Municipal Central Hospital, Lishui, Zhejiang, 323000, China.
| | - Chuan Jiang
- Department of Gastrointestinal Abdominal Hernia Surgery, Lishui Municipal Central Hospital, Lishui, Zhejiang, 323000, China
| | - Jingjing Zheng
- Department of Gastrointestinal Abdominal Hernia Surgery, Lishui Municipal Central Hospital, Lishui, Zhejiang, 323000, China
| | - Dan Wu
- Department of Gastrointestinal Abdominal Hernia Surgery, Lishui Municipal Central Hospital, Lishui, Zhejiang, 323000, China
| | - Laizhen Tou
- Department of Gastrointestinal Abdominal Hernia Surgery, Lishui Municipal Central Hospital, Lishui, Zhejiang, 323000, China
| | - Haifeng Que
- Department of Gastrointestinal Abdominal Hernia Surgery, Lishui Municipal Central Hospital, Lishui, Zhejiang, 323000, China
| | - Zheng Sun
- Department of Gastrointestinal Abdominal Hernia Surgery, Lishui Municipal Central Hospital, Lishui, Zhejiang, 323000, China
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Shannon AB, Mehta R, Mok SR, Lauwers GY, Baldonado JJAR, Fontaine J, Pimiento JM, Sinnamon AJ. Clinical and Pathologic Response to Neoadjuvant Immunotherapy in DNA Mismatch Repair Protein-Deficient Gastroesophageal Cancers. Ann Surg Oncol 2024; 31:8616-8626. [PMID: 39154152 DOI: 10.1245/s10434-024-16030-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 07/29/2024] [Indexed: 08/19/2024]
Abstract
BACKGROUND Mismatch repair deficient (dMMR) gastroesophageal cancers (GEC) are a distinct subgroup. Among patients with locally advanced disease, previous trial data suggest a good response to neoadjuvant immune checkpoint inhibitors (nICI). PATIENTS AND METHODS Since 2019, our institution has routinely performed MMR testing for new GEC cases. Patients diagnosed with GEC (2019-2024) were included in the study. Quantitative data are described as the median and interquartile range (IQR); qualitative data are described as quantities and percentages. RESULTS A total of 24 patients with dMMR GEC were identified following implementation of routine immunohistochemical testing; 14 were potentially resectable with a median follow-up of 14 months (IQR 8-27). All patients underwent pre-treatment positron emission tomography (PET; median SUV 20.9). Among the 14 potentially resectable patients, 4 underwent immediate surgery, 10 were treated with nICI, and 5 underwent surgical resection to date. All regimens included PD-1 inhibitors, with 70% receiving pembrolizumab. Re-staging PET was performed in five patients; the median post-nICI SUV was 5.1 (range 4.7-6.3). All resected specimens had gross ulceration after nICI, but 60% (N = 3) had a pathologic complete response (pCR) following nICI; one patient had a near-complete response (nCR) and one patient had a partial response (pPR). Reduction in SUV was 75% and 82% in the pCR patients, 25% in the nCR patient, and 43% in the pPR patient. CONCLUSIONS dMMR GECs are responsive to nICI in this limited experience, mirroring early clinical trial data. Given persistent metabolic activity and visible ulceration despite pCR, studies should continue to optimize tools for estimating post-nICI pCR in these patients.
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Affiliation(s)
- Adrienne B Shannon
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
| | - Rutika Mehta
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | - Shaffer R Mok
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | - Gregory Y Lauwers
- Department of Anatomic Pathology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | | | - Jacques Fontaine
- Department of Thoracic Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | - Jose M Pimiento
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | - Andrew J Sinnamon
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
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Liu Z, Liu F, Petinrin OO, Wang F, Zhang Y, Wong KC. Uncovering the ceRNA Network Related to the Prognosis of Stomach Adenocarcinoma Among 898 Patient Samples. Biochem Genet 2024; 62:4770-4790. [PMID: 38361095 PMCID: PMC11604743 DOI: 10.1007/s10528-023-10656-7] [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: 02/09/2023] [Accepted: 12/29/2023] [Indexed: 02/17/2024]
Abstract
Stomach adenocarcinoma (STAD) patients are often associated with significantly high mortality rates and poor prognoses worldwide. Among STAD patients, competing endogenous RNAs (ceRNAs) play key roles in regulating one another at the post-transcriptional stage by competing for shared miRNAs. In this study, we aimed to elucidate the roles of lncRNAs in the ceRNA network of STAD, uncovering the molecular biomarkers for target therapy and prognosis. Specifically, a multitude of differentially expressed lncRNAs, miRNAs, and mRNAs (i.e., 898 samples in total) was collected and processed from TCGA. Cytoplasmic lncRNAs were kept for evaluating overall survival (OS) time and constructing the ceRNA network. Differentially expressed mRNAs in the ceRNA network were also investigated for functional and pathological insights. Interestingly, we identified one ceRNA network including 13 lncRNAs, 25 miRNAs, and 9 mRNAs. Among them, 13 RNAs were found related to the patient survival time; their individual risk score can be adopted for prognosis inference. Finally, we constructed a comprehensive ceRNA regulatory network for STAD and developed our own risk-scoring system that can predict the OS time of STAD patients by taking into account the above.
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Affiliation(s)
- Zhe Liu
- Department of Computer Science, City University of Hong Kong, Hong Kong, China
| | - Fang Liu
- College of Chemistry and Chemical Engineering, Central South University, Changsha, China
| | | | - Fuzhou Wang
- Department of Computer Science, City University of Hong Kong, Hong Kong, China
| | - Yu Zhang
- College of Life Sciences, Xinyang Normal University, Xinyang, China
| | - Ka-Chun Wong
- Department of Computer Science, City University of Hong Kong, Hong Kong, China.
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Zhang L, Cui J, Cai M, Li B, Ma G, Wang X, Liu Y, Deng J, Zhang R, Liang H, Yang J. Comparison of short‑term outcomes and 3-year overall survival between robotic and laparoscopic gastrectomy for gastric cancer: a propensity score matching analysis. Acta Chir Belg 2024; 124:478-486. [PMID: 38693890 DOI: 10.1080/00015458.2024.2348256] [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: 12/11/2023] [Accepted: 04/22/2024] [Indexed: 05/03/2024]
Abstract
BACKGROUND Despite the increasing use of robotic gastrectomy (RG) as an alternative to laparoscopic gastrectomy (LG) in treating gastric cancer, controversy remains over the advantages of RG compared to LG and there is a paucity of studies comparing the two techniques regarding patient survival. METHODS In this retrospective cohort study, 675 patients undergoing minimally invasive gastrectomy were recruited from January 2016 to January 2018 (LG: n = 567; RG: n = 108). A one-to-one propensity score matching (PSM) analysis was applied to minimize the selection bias due to confounding factors, yielding 104 patients in each of the RG and LG groups. After matching, the short-term outcomes and 3-year overall survival were compared in the two groups. RESULTS The PSM cohort analysis showed a similar 3-year overall survival between RG and LG groups (p = .249). Concerning the short-term outcomes, the RG compared to LG resulted in lower blood loss (p = .01), lower postoperative complications (p = .001), lower postoperative pain (p = .016), earlier initiation of soft diet (p = .011), shorter hospital stay (p = .012), but higher hospitalization expenses (p = .001). CONCLUSION Our findings suggest that RG may offer advantages in terms of blood loss, surgical complications, recovery time, and pain management compared to LG while maintaining similar overall survival rates. However, RG is associated with higher hospital costs, potentially limiting its wider adoption. Further research, including large, multi-center randomized controlled trials with longer patient follow-up, particularly for advanced gastric cancer, is needed to confirm these findings.
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Affiliation(s)
- Li Zhang
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, P. R. China
| | - Jingli Cui
- Department of General Surgery, Weifang People's Hospital, Weifang, P. R. China
| | - Mingzhi Cai
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, P. R. China
| | - Bin Li
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, P. R. China
| | - Gang Ma
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, P. R. China
| | - Xuejun Wang
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, P. R. China
| | - Yong Liu
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, P. R. China
| | - Jingyu Deng
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, P. R. China
| | - Rupeng Zhang
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, P. R. China
| | - Han Liang
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, P. R. China
| | - Jilong Yang
- Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, P. R. China
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Morais R, Moreira J, Gaspar R, Santos-Antunes J, Marques M, Coelho R, Alves R, Ferreira-Silva J, Dias E, Pereira P, Lopes S, Cardoso H, Sousa-Pinto B, Faria-Ramos I, Gullo I, Carneiro F, Liberal R, Macedo G. Higher frequency of gastric neoplasia in advanced chronic liver disease patients: Impact of screening endoscopy in an intermediate-high risk country. Dig Liver Dis 2024; 56:2133-2142. [PMID: 38811247 DOI: 10.1016/j.dld.2024.04.035] [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: 12/30/2023] [Revised: 04/28/2024] [Accepted: 04/29/2024] [Indexed: 05/31/2024]
Abstract
BACKGROUND The Baveno VII guidelines were proposed to identify which patients could safely avoid screening esophagogastroduodenoscopy (EGD) for gastroesophageal varices. We aimed to evaluate the frequency of gastric neoplasia in compensated advanced chronic liver disease (cACLD) patients who underwent EGD for screening of gastroesophageal varices (GOEV) compared to a healthy population. METHODS Retrospective study that enrolled all cACLD patients who underwent EGD for GOEV screening (January 2008-June 2018) in a tertiary reference center. cACLD patients were compared with asymptomatic healthy individuals who underwent EGD in a private hospital setting (April 2017-March 2018). RESULTS We evaluated 1845 patients (481 cACLD patients, 1364 healthy individuals). A significantly higher frequency of gastric neoplasia was observed in patients with cACLD compared to healthy individuals (4.0% vs. 1.0 %; p < 0.001). Rare histopathological subtypes (WHO Classification) accounted for 28.7 % of gastric carcinoma cases in the cACLD cohort. Seven cases of gastric neoplasia (36.8 % of gastric neoplasia cases in the cACLD patients) were diagnosed in patients who, according to the Baveno VII criteria, would have not been submitted to EGD. CONCLUSION We found an increased frequency of gastric neoplasia in patients with cACLD in comparison with healthy individuals. In countries with intermediate-high risk for GC, continuing to perform EGD could be beneficial.
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Affiliation(s)
- Rui Morais
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal.
| | - João Moreira
- Faculty of Medicine of the University of Porto (FMUP), Portugal
| | - Rui Gaspar
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal
| | - João Santos-Antunes
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal; i3S - Instituto de Investigação e Inovação em Saúde and Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), Portugal
| | - Margarida Marques
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal
| | - Rosa Coelho
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal
| | - Rosa Alves
- Internal Medicine Department, Centro Hospitalar Barreiro Montijo, Portugal
| | - Joel Ferreira-Silva
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal
| | - Emanuel Dias
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal
| | - Pedro Pereira
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal
| | - Susana Lopes
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal
| | - Hélder Cardoso
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal
| | - Bernardo Sousa-Pinto
- MEDCIDS-Department of Community Medicine, Information and Health Decision Sciences; Faculty of Medicine, University of Porto, Porto, Portugal; CINTESIS@RISE-Health Research Network, Faculty of Medicine, University of, Porto, Porto, Portugal
| | - Isabel Faria-Ramos
- Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal
| | - Irene Gullo
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Department of Pathology, Centro Hospitalar Universitário de São João, Portugal; i3S - Instituto de Investigação e Inovação em Saúde and Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), Portugal
| | - Fátima Carneiro
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Department of Pathology, Centro Hospitalar Universitário de São João, Portugal; i3S - Instituto de Investigação e Inovação em Saúde and Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), Portugal
| | - Rodrigo Liberal
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal
| | - Guilherme Macedo
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal
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Li J, He L, Zhang X, Li X, Wang L, Zhu Z, Song K, Wang X. GCclassifier: An R package for the prediction of molecular subtypes of gastric cancer. Comput Struct Biotechnol J 2024; 23:752-758. [PMID: 38304548 PMCID: PMC10831507 DOI: 10.1016/j.csbj.2024.01.010] [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: 10/22/2023] [Revised: 01/14/2024] [Accepted: 01/15/2024] [Indexed: 02/03/2024] Open
Abstract
Gastric cancer (GC) is one of the most commonly diagnosed malignancies, threatening millions of lives worldwide each year. Importantly, GC is a heterogeneous disease, posing a significant challenge to the selection of patients for more optimized therapy. Over the last decades, extensive community effort has been spent on dissecting the heterogeneity of GC, leading to the identification of distinct molecular subtypes that are clinically relevant. However, so far, no tool is publicly available for GC subtype prediction, hindering the research into GC subtype-specific biological mechanisms, the design of novel targeted agents, and potential clinical applications. To address the unmet need, we developed an R package GCclassifier for predicting GC molecular subtypes based on gene expression profiles. To facilitate the use by non-bioinformaticians, we also provide an interactive, user-friendly web server implementing the major functionalities of GCclassifier. The predictive performance of GCclassifier was demonstrated using case studies on multiple independent datasets.
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Affiliation(s)
- Jiang Li
- Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region of China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region of China
- Department of Biomedical Sciences, City University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Lingli He
- Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region of China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region of China
- Department of Biomedical Sciences, City University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Xianrui Zhang
- Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region of China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region of China
- Department of Biomedical Sciences, City University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Xiang Li
- Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region of China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region of China
| | - Lishi Wang
- Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region of China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region of China
| | - Zhongxu Zhu
- Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region of China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region of China
- HIM-BGI Omics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
| | - Kai Song
- Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region of China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region of China
- Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, Region of China
| | - Xin Wang
- Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region of China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region of China
- Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, Region of China
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Silva ARC, Alicandro G, Guandalini VR, da Fonseca Grili PP, Assumpção PP, Barbosa MS, de Sant'Ana RO, Coimbra FJF, Curado MP. Exploring the link between dietary patterns and gastric adenocarcinoma in Brazil: a mediation analysis. BMC Med 2024; 22:562. [PMID: 39609810 PMCID: PMC11603788 DOI: 10.1186/s12916-024-03785-2] [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: 05/08/2024] [Accepted: 11/19/2024] [Indexed: 11/30/2024] Open
Abstract
BACKGROUND The causal pathway between different dietary patterns (DPs) and gastric adenocarcinoma (GA) remains largely unexplored. The study aimed to identify DPs and evaluate how selected nutrients mediate the relationship between DPs and GA. METHODS This multicenter case-control study in Brazil involved 1751 participants (600 cases, 377 endoscopic controls, and 774 hospital controls). DPs were identified through exploratory factor analysis. A counterfactual-based mediation analysis was performed to decompose the total effect of DPs on GA into direct and indirect effects mediated by saturated fatty acids, added sugars, total fiber, and sodium intakes. Effects were expressed as ORs and 95% CIs. RESULTS Two DPs were identified-"unhealthy dietary pattern" (UDP) and "healthy dietary pattern" (HDP), which were associated with an increased and decreased risk of GA, respectively. Added sugars partly mediated the association between UDP and GA (percentage mediated between 7.3 and 21.7%), while sodium intake mediated most of the association between HDP and GA (percentage mediated between 52.4 and 100%). No significant mediating effects were detected for saturated fatty acids and total fiber. CONCLUSIONS This study contributes innovative insights into the DPs-GA relationships, highlighting the significant mediating roles of sodium and added sugars, offering valuable information for preventive strategies and public health interventions targeting GA.
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Affiliation(s)
| | - Gianfranco Alicandro
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
- Pediatric Department, Cystic Fibrosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Valdete Regina Guandalini
- Health Sciences Center, Postgraduate Program in Nutrition and Health, Federal University of Espírito Santo, Vitória, Brazil
- Department of Integrated Education, Health Sciences Center, Federal University of Espírito Santo, Vitória, Brazil
| | | | | | - Mônica Santiago Barbosa
- Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiânia, Brazil
| | - Rosane Oliveira de Sant'Ana
- Division of Clinical Oncology, Ceará Cancer Institute, Fortaleza, Brazil
- University of Fortaleza, Fortaleza, Brazil
| | - Felipe José Fernández Coimbra
- Graduate Program of A.C.Camargo Cancer Center, São Paulo, Brazil
- Department of Surgical Oncology, A.C.Camargo Cancer Center, São Paulo, Brazil
| | - Maria Paula Curado
- Graduate Program of A.C.Camargo Cancer Center, São Paulo, Brazil.
- Cancer Epidemiology and Statistics Group, International Research Center, A.C.Camargo Cancer Center, São Paulo, Brazil.
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Matysiak K, Hojdis A, Szewczuk M. Controlling Nutritional Status (CONUT) Score as Prognostic Indicator in Stage IV Gastric Cancer with Chronic Intestinal Failure. Nutrients 2024; 16:4052. [PMID: 39683445 DOI: 10.3390/nu16234052] [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: 10/27/2024] [Revised: 11/21/2024] [Accepted: 11/25/2024] [Indexed: 12/18/2024] Open
Abstract
The management of chronic intestinal failure (CIF) secondary to advanced gastric cancer poses clinical challenges. This study explores the correlation between the Controlling Nutritional Status (CONUT) index and survival in patients with TNM stage IV gastric cancer on home parenteral nutrition (HPN). METHODS From 2015 to 2023, 410 patients (37% women, 63% men) with CIF due to advanced gastric cancer were assessed using CONUT scores, BMI, and biochemical tests. The Cox proportional hazards model was used to evaluate the impact of covariates on survival. Logistic regression categorized malnutrition levels by CONUT scores, with performance evaluated using precision, recall, and F1 scores. A p-value < 0.001 was statistically significant. RESULTS The CONUT scores were independent predictors of survival, with higher CONUT scores increasing mortality risk (HR = 2.073, 95% CI: 1.815-2.369, p < 0.001). The model achieved an overall accuracy of 71%, indicating correct classification for the majority of cases. CONCLUSIONS CONUT scores are key predictors of survival in patients receiving HPN for CIF due to stage IV gastric cancer.
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Affiliation(s)
- Konrad Matysiak
- Centre for Intestinal Failure, Poznan University of Medical Sciences, 60-355 Poznań, Poland
| | - Aleksandra Hojdis
- Department of Gastroenterology, Poznan University Hospital, 60-355 Poznań, Poland
| | - Magdalena Szewczuk
- Department of Gastroenterology, Poznan University Hospital, 60-355 Poznań, Poland
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Wang J, Liu B, Chen J. Validity of the Global Leadership Initiative on Malnutrition criteria in East Asian patients with gastric cancer: a comprehensive narrative review. Front Nutr 2024; 11:1462487. [PMID: 39634550 PMCID: PMC11614637 DOI: 10.3389/fnut.2024.1462487] [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: 07/10/2024] [Accepted: 11/04/2024] [Indexed: 12/07/2024] Open
Abstract
Background Malnutrition is a significant public health issue for patients with gastric cancer, particularly in East Asia, the region most affected globally. In response to the absence of adequate tools for assessing nutritional status, the Global Leadership Initiative on Malnutrition (GLIM) criteria were established in 2018, aiming to standardize the diagnosis of malnutrition. However, there is no consensus on the value of GLIM criteria for evaluating the nutritional status of patients with gastric cancer in East Asia. Given these facts, our study aimed to assess the validity of the GLIM criteria in East Asian patients with gastric cancer. Methods We conducted a rapid critical review of available literature, summarizing the existing problems in GLIM applications and possible improvement directions. After systematically summarizing the literature published in PubMed, Web of Science, and Cochrane Library, a total of 13 articles involving 7,679 cases were included in this study. Results The results indicated a lack of sufficient data on sensitivity and specificity to fully validate the GLIM criteria for diagnosing malnutrition in East Asian patients with gastric cancer. Additionally, some studies have reported moderate agreement between the GLIM and the PG-SGA. Furthermore, malnutrition defined by GLIM is a risk factor for short and long-term outcomes in East Asian patients with gastric cancer. However, the prognostic effect of moderate malnutrition on these patients remains controversial. Conclusion Despite being in the early application stages, GLIM has shown promising potential in diagnosing and predicting the prognosis of malnutrition. However, future research should incorporate more comprehensive validity parameters, including sensitivity, specificity, and PPV/NPV, to achieve a more thorough understanding of GLIM's diagnostic efficacy. Furthermore, further optimization of GLIM is necessary to address the needs of more diverse populations and situations.
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Affiliation(s)
- Jian Wang
- The Third Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Bingyue Liu
- Hangzhou Zhanshi Traditional Chinese Hospital of Orthopaedics, Hangzhou, Zhejiang, China
| | - Jianxin Chen
- Department of Medical Oncology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, China
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Jiang J, Li D, Li F, Li H, Zhang X, Feng L. Catechin promotes endoplasmic reticulum stress-mediated gastric cancer cell apoptosis via NOX4-induced reactive oxygen species. Mol Cell Biochem 2024:10.1007/s11010-024-05138-2. [PMID: 39565530 DOI: 10.1007/s11010-024-05138-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 10/07/2024] [Indexed: 11/21/2024]
Abstract
Catechin, a polyphenolic compound in various foods and beverages, shows strong anti-cancer effects against gastric cancer (GC) cells. This study explored the effect of catechin on GC cell apoptosis and endoplasmic reticulum (ER) stress. GC cells were treated with different catechin concentrations to assess effects on cell viability, LDH release, invasion, migration, apoptosis, intracellular calcium (Ca2⁺), ER stress markers, and reactive oxygen species (ROS). siRNA knockdown targeted GRP78, PERK, CHOP, and NOX4 to examine their roles in catechin-induced ER stress and apoptosis. Catechin treatment significantly reduced GC cell viability, increased LDH release, and induced apoptosis dose-dependently. Catechins elevated intracellular Ca2⁺ and ER stress markers. Co-treatment with thapsigargin (TG) intensified these effects, implicating ER stress in apoptosis. Knocking down GRP78, PERK, and CHOP mitigated catechin-induced apoptosis and restored viability. Additionally, catechins raised ROS levels, while co-treatment with Diphenyleneiodonium (DPI) or N-acetylcysteine (NAC) lowered ROS, cell damage, and ER stress markers. NOX4 knockdown countered catechin-induced viability loss and upregulated CHOP and cleaved caspase-3. Catechin induces apoptosis in GC cells through ER stress and ROS generation. Key mediators include GRP78, PERK, CHOP, and NOX4, suggesting potential therapeutic targets for enhancing catechin efficacy in GC treatment.
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Affiliation(s)
- Jun Jiang
- Endoscopy Center, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Shanghai, 201100, China
| | - Deming Li
- Endoscopy Center, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Shanghai, 201100, China
| | - Fan Li
- Endoscopy Center, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Shanghai, 201100, China
| | - Huanqing Li
- Endoscopy Center, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Shanghai, 201100, China.
| | - Xiaohong Zhang
- Endoscopy Center, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Shanghai, 201100, China.
| | - Li Feng
- Endoscopy Center, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Shanghai, 201100, China.
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Ma L, Hu X, Zhang W, Qi D, Chen L, Yin M. Weifuchun suppresses the malignancy of gastric cancer cells by targeting KPNA2 through miR-26a-5p-mediated destabilization and the deactivation of the MAPK signaling pathway. JOURNAL OF ETHNOPHARMACOLOGY 2024; 334:118538. [PMID: 38992399 DOI: 10.1016/j.jep.2024.118538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Revised: 05/12/2024] [Accepted: 07/07/2024] [Indexed: 07/13/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Weifuchun (WFC) is a Traditional Chinese Medicine commonly used for treating atrophic gastritis and intestinal metaplasia. Till date, its antitumor effect on gastric cancer (GC) and the underlying mechanisms of the effect remains unelucidated. AIM OF THE STUDY We aim to investigate if WFC can suppress the malignancy of stomach cancer cells and dissect the molecular basis and the associated molecular and cellular features. MATERIALS AND METHODS Stomach cancer cell lines and normal gastric epithelial cells were treated with WFC. CCK8 assay, caspase-3 activity assay, adhesion assay, microRNA database analysis, transfection, RT-PCR, Western Blotting, signaling pathway analysis, and in vivo GC model were employed to examine the changes in the features of the gastric cancer cells and the molecular mechanisms of the effect of WFC. RESULTS Here we present data demonstrating that WFC suppresses the malignant cellular phenotypes of GC and this inhibitory effect is mediated by downregulating the expression of oncogenic KPNA2. Furthermore, WFC downregulates KPNA2 through miR-26a-5p-mediated gene silencing and the deactivated phosphorylation dynamics of mitogen-activated protein kinase (MAPK). The suppressive effect of WFC on stomach cancer cell behavior was further confirmed in animal model. CONCLUSION Therefore, WFC can exert inhibitory effect on the malignancy of GC cells by reducing the levels of KPNA2. Moreover, the miR-26a-5p rescue and the deactivation MAPK pathway induced by WFC result in the downregulation of KPNA2 expression. Thus, our findings suggest WFC as a potential treatment option against GC.
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Affiliation(s)
- Lvli Ma
- Hangzhou Huqingyu Hall Pharmaceutical Co., Ltd., Hangzhou, China
| | - Xu Hu
- Tongde Hospital of Zhejiang Province, Hangzhou, China
| | - Wei Zhang
- Hangzhou Huqingyu Hall Pharmaceutical Co., Ltd., Hangzhou, China.
| | - Daqing Qi
- Hangzhou Huqingyu Hall Pharmaceutical Co., Ltd., Hangzhou, China
| | - Linhui Chen
- Hangzhou Huqingyu Hall Pharmaceutical Co., Ltd., Hangzhou, China
| | - Minfang Yin
- Zhejiang Provincial People's Hospital, Hangzhou, China
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Koopaie M, Arian-Kia S, Manifar S, Fatahzadeh M, Kolahdooz S, Davoudi M. Expression of Salivary miRNAs, Clinical, and Demographic Features in the Early Detection of Gastric Cancer: A Statistical and Machine Learning Analysis. J Gastrointest Cancer 2024; 56:15. [PMID: 39520622 DOI: 10.1007/s12029-024-01136-1] [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] [Accepted: 10/27/2024] [Indexed: 11/16/2024]
Abstract
OBJECTIVE Gastric cancer ranks as one of the top five deadliest cancers worldwide and is often diagnosed at late stages. Analysis of saliva may provide a non-invasive approach for detection of malignancies in organs associated with the oral cavity. This research aims to analyze salivary microRNA expression together with clinical and demographic features with the aim of diagnosing gastric cancer. MATERIALS The study included 19 patients with early-stage gastric cancer and 19 healthy controls. Saliva samples were collected and processed for RNA isolation. Salivary expression of miR-223-3p and miR-21-5p were measured using quantitative reverse-transcription polymerase chain reaction (RT-qPCR). Receiver operating characteristic (ROC) curves were generated to evaluate the accuracy of diagnostic models. Machine learning algorithms, multiple logistic regression, and principal component analysis (PCA) were used to assess the predictive power of miRNAs in conjunction with clinical-demographic features. RESULTS Significant upregulation of miR-223-3p and downregulation of miR-21-5p in saliva were observed in patients with gastric cancer. The area under ROC curve (AUC) values for salivary miR-21-5p, salivary miR-223-3p, and their multiple logistic regression were determined to be 0.723, 0.791, and 0.850, respectively. The AUC for multiple logistic regression model was 0.919. The PCA model led to the highest diagnostic odds ratio (DOR) of 134.33 (sensitivity = 0.785, specificity = 1.00, AUC = 903). Application of machine learning methods, and in particular a random forest algorithm, showed high accuracy in diagnosing patients with gastric cancer (sensitivity = 1.00, specificity = 0.857, AUC = 0.93). CONCLUSION The application of validated salivary diagnostics in clinical practice could help facilitate earlier diagnosis of gastric cancer and improve medical outcome. Expression of miR-21 and miR-223-3p in saliva together with clinical and demographic features, appears promising in screening for GC.
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Affiliation(s)
- Maryam Koopaie
- Department of Oral Medicine, School of Dentistry, Tehran University of Medical Sciences, North Kargar St, P.O.BOX:14395-433, Po. Code, Tehran, 14399-55991, Iran.
| | - Sasan Arian-Kia
- Department of Oral Medicine, School of Dentistry, Tehran University of Medical Sciences, North Kargar St, P.O.BOX:14395-433, Po. Code, Tehran, 14399-55991, Iran
| | - Soheila Manifar
- Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahnaz Fatahzadeh
- Division of Oral Medicine, Department of Oral Medicine, Rutgers School of Dental Medicine, 110 Bergen Street, Newark, NJ, 07103, USA
| | - Sajad Kolahdooz
- Universal Scientific Education and Research Network (USERN), Tehran University of Medical Sciences, Tehran, Iran
| | - Mansour Davoudi
- Department of Computer Science and Engineering and IT, School of Electrical and Computer Engineering, Shiraz University, Shiraz, Iran
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Kashyap D, Roy R, Varshney N, Baral B, Bagde PH, Kandpal M, Kumar S, Kar P, Jha HC. Withania somnifera extract reduces gastric cancerous properties through inhibition of gankyrin in cellular milieu produced by Helicobacter pylori and Epstein Barr virus. J Biomol Struct Dyn 2024; 42:9399-9415. [PMID: 37655681 DOI: 10.1080/07391102.2023.2252096] [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: 02/07/2023] [Accepted: 08/18/2023] [Indexed: 09/02/2023]
Abstract
Helicobacter pylori and Epstein Barr virus (EBV) are group1 carcinogens and their role in Gastric cancer (GC) is well established. Previously we have shown that H. pylori and EBV appears to support aggressive gastric oncogenesis through the upregulation of oncoprotein Gankyrin. Natural plant active molecules have the potential to interrupt oncogenesis. Herein, we investigated the potential of Withania somnifera root extract (WSE) as a possible chemotherapeutic agent against host oncoprotein Gankyrin whose expression was altered by H. pylori and EBV-associated modified cellular milieu. The results show that WSE does not have any inhibitory effect on H. pylori and EBV-associated gene transcripts except for the lmps (lmp1, lmp2a, and lmp2B). Moreover, the WSE exert their anticancer activity via host cellular response and decreased the expression of cell-migratory (mmp3 and mmp7); cell-cycle regulator (pcna); antiapoptotic gene (bcl2); increased the expression of the proapoptotic gene (apaf1 and bax); and tumor suppressor (p53, prb, and pten). Knockdown of Gankyrin followed by the treatment of WSE also decreases the expression of TNF-ɑ, Akt, and elevated the expression of NFkB, PARP, Casp3, and Casp9. WSE also reduces cell migration, and genomic instability and forced the cells to commit programmed cell death. Moreover, molecular simulation studies revealed that out of eight active compounds of WSE, only four compounds such as withaferin A (WFA), withanoside IV (WA4), withanolide B (WNB), and withanolide D (WND) showed direct stable interaction with Gankyrin. This article reports for the first time that treatment of WSE decreased the cancerous properties through host cellular response modulation in gastric epithelial cells coinfected with H. pylori and EBV.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Dharmendra Kashyap
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India
| | - Rajarshi Roy
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India
| | - Nidhi Varshney
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India
| | - Budhadev Baral
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India
| | - Pranit Hemant Bagde
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India
| | - Meenakshi Kandpal
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India
| | - Sachin Kumar
- Himalayan School of Biosciences, Swami Rama Himalayan University, Dehradun, India
| | - Parimal Kar
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India
| | - Hem Chandra Jha
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India
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47
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Lyu TD, Luo MP, Hu HW. Nomogram for predicting 10-year postoperative recurrence of stage I gastric cancer. Transl Cancer Res 2024; 13:5497-5508. [PMID: 39525020 PMCID: PMC11543093 DOI: 10.21037/tcr-24-692] [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: 04/26/2024] [Accepted: 08/11/2024] [Indexed: 11/16/2024]
Abstract
Background With the advancement of various auxiliary examination techniques, the detection rate of stage I gastric cancer has gradually increased, and its clinical first-choice treatment is surgery. Although patients with stage I gastric cancer generally have a good postoperative survival rate, there is still a certain probability of recurrence. Given the large number of gastric cancer cases, there is a vast population of patients with stage I disease. We are aiming to identify the risk factors for postoperative recurrence of stage I gastric cancer and to establish a reliable predictive model to assess the risk of recurrence in the population for clinical practice. Methods In this retrospective cohort study, we utilized the Surveillance, Epidemiology, and End Results (SEER) database to investigate predictive factors for recurrence among stage I gastric cancer patients who underwent curative gastrectomy between 2000 and 2018. The cohort was divided into training and validation sets for the development and validation of a nomogram. Prognostic factors were evaluated through univariate and multivariate Cox regression analyses. Significant variables identified by the concordance index (C-index) and calibration plots were used to construct nomograms predicting the probability of 5- and 10-year recurrence. Results Risk factors for recurrence included sex, age, race, histology, tumor size, American Joint Committee on Cancer Tumor (AJCC T) and primary site, which were used to construct the nomogram. The C-index for both the training and validation cohorts indicated that the nomogram possessed good calibration and discrimination abilities in predicting the probability of 5- and 10-year recurrence after curative surgery for stage I gastric cancer. Conclusions This study established a reliable predictive model for recurrence following curative gastrectomy in stage I gastric cancer based on a population cohort. The findings of this study have the potential to significantly impact clinical practice by providing clinicians with tools for personalized risk assessment and for making informed treatment decisions.
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Affiliation(s)
- Tong-Dan Lyu
- Department of Medical Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China
| | - Ming-Peng Luo
- Department of Medical Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China
| | - Hao-Wei Hu
- Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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48
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Wen H, Mi Y, Li F, Xue X, Sun X, Zheng P, Liu S. Identifying the signature of NAD+ metabolism-related genes for immunotherapy of gastric cancer. Heliyon 2024; 10:e38823. [PMID: 39640811 PMCID: PMC11620085 DOI: 10.1016/j.heliyon.2024.e38823] [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: 06/29/2023] [Revised: 09/03/2024] [Accepted: 09/30/2024] [Indexed: 12/07/2024] Open
Abstract
NAD (Nicotinamide Adenine Dinucleotide) -related metabolic reprogramming in tumor cells involves multiple vital cellular processes. However, the role of NAD metabolism in immunity and the prognosis of gastric cancer (GC) remains not elucidated. Here we identified and clustered 33 NAD + metabolism-related genes (NMRGs) based on 808 GC samples from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Survival analysis between different groups found a poor prognosis in the GC patients with high NMRGs expression. Gene SGCE, APOD, and PPP1R14A were identified and performed high expression in GC samples, while the qRT-PCR results further confirmed that their expression levels in GC cell lines were significantly higher than those from normal human gastric mucosa epithelial cells. Based on the single-cell analysis, Gene SGCE, APOD, and PPP1R14A can potentially be novel biomarkers of tumor-associated fibroblasts (CAFs). In parallel, the proliferation and migration of GC cells were significantly hampered following the knockdown of SGCE, APOD, and PPP1R14A, particularly APOD, we confirmed that APOD knockdown can inhibit β-catenin and N-cadherin expression, while promote E-cadherin expression. This study unveils a novel NMRGs-related gene signature, highlighting APOD as a prognostic biomarker linked to the tumor microenvironment. APOD drives GC cell proliferation and metastasis through the Wnt/β-catenin/EMT signaling pathway, establishing it as a promising therapeutic target for GC patients.
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Affiliation(s)
- Huijuan Wen
- Henan Key Laboratory of Helicobacter pylori & Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Academy of medical science, Zhengzhou University, Zhengzhou, 450052, China
| | - Yang Mi
- Henan Key Laboratory of Helicobacter pylori & Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Fazhan Li
- Henan Key Laboratory of Helicobacter pylori & Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Academy of medical science, Zhengzhou University, Zhengzhou, 450052, China
| | - Xia Xue
- Henan Key Laboratory of Helicobacter pylori & Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Xiangdong Sun
- Henan Key Laboratory of Helicobacter pylori & Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Academy of medical science, Zhengzhou University, Zhengzhou, 450052, China
| | - Pengyuan Zheng
- Henan Key Laboratory of Helicobacter pylori & Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Academy of medical science, Zhengzhou University, Zhengzhou, 450052, China
- Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Simeng Liu
- Henan Key Laboratory of Helicobacter pylori & Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
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49
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Begolli R, Patouna A, Vardakas P, Xagara A, Apostolou K, Kouretas D, Giakountis A. Deciphering the Landscape of GATA-Mediated Transcriptional Regulation in Gastric Cancer. Antioxidants (Basel) 2024; 13:1267. [PMID: 39456519 PMCID: PMC11504088 DOI: 10.3390/antiox13101267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 10/11/2024] [Accepted: 10/16/2024] [Indexed: 10/28/2024] Open
Abstract
Gastric cancer (GC) is an asymptomatic malignancy in early stages, with an invasive and cost-ineffective diagnostic toolbox that contributes to severe global mortality rates on an annual basis. Ectopic expression of the lineage survival transcription factors (LS-TFs) GATA4 and 6 promotes stomach oncogenesis. However, LS-TFs also govern important physiological roles, hindering their direct therapeutic targeting. Therefore, their downstream target genes are particularly interesting for developing cancer-specific molecular biomarkers or therapeutic agents. In this work, we couple inducible knockdown systems with chromatin immunoprecipitation and RNA-seq to thoroughly detect and characterize direct targets of GATA-mediated transcriptional regulation in gastric cancer cells. Our experimental and computational strategy provides evidence that both factors regulate the expression of several coding and non-coding RNAs that in turn mediate for their cancer-promoting phenotypes, including but not limited to cell cycle, apoptosis, ferroptosis, and oxidative stress response. Finally, the diagnostic and prognostic potential of four metagene signatures consisting of selected GATA4/6 target transcripts is evaluated in a multi-cancer panel of ~7000 biopsies from nineteen tumor types, revealing elevated specificity for gastrointestinal tumors. In conclusion, our integrated strategy uncovers the landscape of GATA-mediated coding and non-coding transcriptional regulation, providing insights regarding their molecular and clinical function in gastric cancer.
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Affiliation(s)
- Rodiola Begolli
- Laboratory of Molecular Biology and Genomics, Department of Biochemistry and Biotechnology, University of Thessaly, Biopolis, Mezourlo, 41500 Larissa, Greece
| | - Anastasia Patouna
- Laboratory of Animal Physiology, Department of Biochemistry and Biotechnology, University of Thessaly, Biopolis, Mezourlo, 41500 Larissa, Greece
| | - Periklis Vardakas
- Laboratory of Animal Physiology, Department of Biochemistry and Biotechnology, University of Thessaly, Biopolis, Mezourlo, 41500 Larissa, Greece
| | - Anastasia Xagara
- Laboratory of Oncology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Mezourlo, 41110 Larissa, Greece
| | - Kleanthi Apostolou
- Laboratory of Molecular Biology and Genomics, Department of Biochemistry and Biotechnology, University of Thessaly, Biopolis, Mezourlo, 41500 Larissa, Greece
| | - Demetrios Kouretas
- Laboratory of Animal Physiology, Department of Biochemistry and Biotechnology, University of Thessaly, Biopolis, Mezourlo, 41500 Larissa, Greece
| | - Antonis Giakountis
- Laboratory of Molecular Biology and Genomics, Department of Biochemistry and Biotechnology, University of Thessaly, Biopolis, Mezourlo, 41500 Larissa, Greece
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50
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Tang W, Ma X. Application of large-scale and multicohort plasma proteomics data to discover novel causal proteins in gastric cancer. Discov Oncol 2024; 15:570. [PMID: 39422802 PMCID: PMC11489397 DOI: 10.1007/s12672-024-01460-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Accepted: 10/14/2024] [Indexed: 10/19/2024] Open
Abstract
PURPOSES Gastric cancer (GC) is one of the most common malignant tumors threatening human beings and has a poor prognosis. Therefore, exploring unveiled biomarkers or therapeutic targets for the diagnosis and treatment of GC is crucial. METHODS A total of 5772 protein quantitative trait loci (pQTL) were aggregated from four latest large-scale proteomics cohorts. Two-sample Mendelian randomization (two-sample MR) was utilized to identify the causal effect of blood plasma proteins on GC. Heterogeneity, pleiotropy, and directionality analyses were employed to evaluate proteins identified via two-sample MR. The robustness of results was further validated via colocalization. The drug targets of proteins were evaluated to reveal the compounds that can interfere with these proteins. RESULTS Ten proteins with potential causations in relation to GC were identified: LY6D, SLURP1, MLN, PSCA, THSD1, CFTR, PPM1B, KDM3A, TSC1, and HCG22. Among these proteins, LY6D, SLURP1, and THSD1 were considered as the most reliable biomarkers of GC due to their significant H4 posterior probabilities in colocalization analysis and absence of pleiotropy. Compound 35, nitrosamide, and 0175029-0000 were potential drugs or small molecules targeting LY6D, SLURP1, and THSD1, respectively. CONCLUSION This study identified several plasma proteins as potential biomarkers of GC and provided data support and new insights into the early diagnosis, intervention, and therapeutic targets of GC.
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Affiliation(s)
- Weihao Tang
- College of Liberal Arts and Sciences, University of Florida, Gainesville, USA
| | - Xiaoke Ma
- School of Computer Science and Technology, Xidian University, Xi'an, China.
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