Gastric Cancer最新文献

{"title":"Predicting chemotherapy responsiveness in gastric cancer through machine learning analysis of genome, immune, and neutrophil signatures.","authors":"Shota Sasagawa, Yoshitaka Honma, Xinxin Peng, Kazuhiro Maejima, Koji Nagaoka, Yukari Kobayashi, Ayako Oosawa, Todd A Johnson, Yuki Okawa, Han Liang, Kazuhiro Kakimi, Yasuhide Yamada, Hidewaki Nakagawa","doi":"10.1007/s10120-024-01569-4","DOIUrl":"10.1007/s10120-024-01569-4","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer is a major oncological challenge, ranking highly among causes of cancer-related mortality worldwide. This study was initiated to address the variability in patient responses to combination chemotherapy, highlighting the need for personalized treatment strategies based on genomic data.</p><p><strong>Methods: </strong>We analyzed whole-genome and RNA sequences from biopsy specimens of 65 advanced gastric cancer patients before their chemotherapy treatment. Using machine learning techniques, we developed a model with 123 omics features, such as immune signatures and copy number variations, to predict their chemotherapy outcomes.</p><p><strong>Results: </strong>The model demonstrated a prediction accuracy of 70-80% in forecasting chemotherapy responses in both test and validation cohorts. Notably, tumor-associated neutrophils emerged as significant predictors of treatment efficacy. Further single-cell analyses from cancer tissues revealed different neutrophil subgroups with potential antitumor activities suggesting their usefulness as biomarkers for treatment decisions.</p><p><strong>Conclusions: </strong>This study confirms the utility of machine learning in advancing personalized medicine for gastric cancer by identifying tumor-associated neutrophils and their subgroups as key indicators of chemotherapy response. These findings could lead to more tailored and effective treatment plans for patients.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"228-244"},"PeriodicalIF":6.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive histopathological analysis of gastric cancer in European and Latin America populations reveals differences in PDL1, HER2, p53 and MUC6 expression.","authors":"Carolina Martínez-Ciarpaglini, Rita Barros, Carmelo Caballero, Hugo Boggino, Lorena Alarcón-Molero, Bárbara Peleteiro, Erika Ruiz-García, Edith Fernandez-Figueroa, Roberto Herrera-Goepfert, Consuelo Díaz-Romero, Rui Ferreira, Tessa S Groen-van Schooten, Cinthia Gauna, Rita Pereira, Daniel Cantero, Horacio Lezcano, Federico Esteso, Juan O Connor, Arnoldo Riquelme, Gareth I Owen, Marcelo Garrido, Juan Carlos Roa, Fiorella Ruiz-Pace, Ana Vivancos, Marc Diez-García, Maria Alsina, Judit Matito, Agatha Martin, Marina Gómez, Ester Castillo, Maria Vila, João Santos-Antunes, Andreia Costa, Florian Lordick, Judith Farrés, Brenda Palomar-De Lucas, Manuel Cabeza-Segura, Rosanna Villagrasa, Elena Jimenez-Martí, Ana Miralles-Marco, Rodrigo Dienstmann, Sarah Derks, Ceu Figueiredo, Andrés Cervantes, Fátima Carneiro, Tania Fleitas-Kanonnikoff","doi":"10.1007/s10120-024-01578-3","DOIUrl":"10.1007/s10120-024-01578-3","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Material and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"160-173"},"PeriodicalIF":6.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"rs762855 single nucleotide polymorphism modulates the risk for diffuse-type gastric cancer in females: a genome-wide association study in the Korean population.","authors":"Kyungtaek Park, Cheol Min Shin, Nayoung Kim, Sungho Won, Chin-Hee Song, Jung Hun Ohn, Sejoon Lee, Ji Hyun Park, Ga-Eun Yie, Seung Joo Kang, Joo Sung Kim, Dong Ho Lee","doi":"10.1007/s10120-024-01575-6","DOIUrl":"10.1007/s10120-024-01575-6","url":null,"abstract":"<p><strong>Background: </strong>Intestinal-type gastric cancer (IGC) and diffuse-type gastric cancer (DGC) exhibit different prevalence rates between sexes. While environmental factors like Helicobacter pylori infection and alcohol consumption contribute to these differences, they do not fully account for them, suggesting a role for host genetic factors.</p><p><strong>Methods: </strong>We conducted a meta-analysis to explore associations between single nucleotide polymorphisms (SNPs) and the risk of IGC or DGC. The analysis included the SNUBH cohort (998 participants: 159 DGCs, 303 IGCs, 4,962,361 variants) and the GC_HC cohort (6,233 participants: 389 DGCs, 405 IGCs, 4,541,617 variants). Significant variants were validated in the SNUBH2_AA cohort (5,511 participants: 40 DGCs, 49 IGCs, 3,668,632 variants).</p><p><strong>Results: </strong>The meta-analysis identified that rs762855 (chr4:3,074,795; hg19) is significantly associated with DGC risk in females (OR [95% CI]: 1.758 [1.438-2.150], P = 3.91 × 10^-8), a finding replicated in the SNUBH2_AA datasets (OR [95% CI]: 3.356 [1.031-10.92], P = 4.43 × 10^-2). Gene-set and transcriptomic analyses revealed that the Myb/SANT DNA Binding Domain Containing 1 (MSANTD1) gene is significantly linked to DGC susceptibility in females. In addition, Mendelian randomization analyses suggested that increased serum total protein and non-albumin protein (NAP) levels elevate DGC risk in females (P < 0.05), but not in males.</p><p><strong>Conclusion: </strong>The rs762855 SNP, MSANTD1, and serum NAP levels are associated with DGC risk in Korean females.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"145-159"},"PeriodicalIF":6.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and clinicopathological features of microsatellite instability-high metastatic or recurrent gastric and esophagogastric junction cancer: WJOG13320GPS.","authors":"Azusa Komori, Shuichi Hironaka, Shigenori Kadowaki, Seiichiro Mitani, Mitsuhiro Furuta, Takeshi Kawakami, Akitaka Makiyama, Naoki Takegawa, Keiji Sugiyama, Hidekazu Hirano, Takayuki Ando, Tomohiro Matsushima, Akihiko Chida, Tomomi Kashiwada, Masato Komoda, Toshihiko Matsumoto, Hisanobu Oda, Hiroshi Yabusaki, Hisato Kawakami, Kentaro Yamazaki, Narikazu Boku, Ichinosuke Hyodo, Kenichi Yoshimura, Kei Muro","doi":"10.1007/s10120-024-01579-2","DOIUrl":"10.1007/s10120-024-01579-2","url":null,"abstract":"<p><strong>Background: </strong>Microsatellite instability (MSI)-high tumors represent a distinct, small-fraction subtype in esophagogastric junction cancer or gastric cancer (GC), yet their clinical significance remains poorly understood. This study aimed to investigate the prevalence and clinicopathological features of chemotherapy-naïve metastatic or recurrent MSI-high GC as a prescreening study for a phase II trial of nivolumab plus ipilimumab.</p><p><strong>Methods: </strong>Key inclusion criteria included metastatic or recurrent adenocarcinoma of GC, ECOG performance status of 0 or 1, and no prior systemic therapy for metastatic or recurrent disease. MSI status was tested using multiplex PCR fragment analysis (MSI Testing Kit, FALCO). The primary endpoint was the prevalence of MSI-high GC.</p><p><strong>Results: </strong>Between October 2020 and October 2022, 930 eligible patients from 75 centers in Japan were analyzed. The prevalence of MSI-high GC was 5.6% (95% CI 4.2-7.3). MSI-high GC was more frequently observed in females than males (9.6% vs 3.8%, p < 0.001), patients aged ≥ 70 years compared to those < 70 years (8.0% vs 2.8%, p < 0.001), in the lower stomach than other locations (10.5% vs 3.2%, p < 0.001), HER2-negative tumors than HER2-positive tumors (6.5% vs 1.8%, p = 0.02), and in patients without liver metastasis than those with liver metastasis (6.9% vs 2.2%, p = 0.004).</p><p><strong>Conclusions: </strong>The prevalence of MSI-high tumors among chemotherapy-naïve patients with unresectable GC was 5.6%. These tumors were associated with female sex, older age, lower stomach, HER2-negative, and absence of liver metastasis. These findings would help assuming MSI-high tumors and may have significant implications for clinical practice and studies targeting this GC subtype.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"301-308"},"PeriodicalIF":6.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor infiltration of inactive CD8 + T cells was associated with poor prognosis in Gastric Cancer.","authors":"Naoki Katayama, Kenoki Ohuchida, Kiwa Son, Chikanori Tsutsumi, Yuki Mochida, Shoko Noguchi, Chika Iwamoto, Nobuhiro Torata, Kohei Horioka, Koji Shindo, Yusuke Mizuuchi, Naoki Ikenaga, Kohei Nakata, Yoshinao Oda, Masafumi Nakamura","doi":"10.1007/s10120-024-01577-4","DOIUrl":"10.1007/s10120-024-01577-4","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) shows limited response to immune checkpoint inhibitors due to its complex tumor immune microenvironment (TIME). This study explores the functions of various immune cells in the complex TIME in GC.</p><p><strong>Methods: </strong>We assessed CD8 + T-cell infiltration of GC tissues by immunohistochemistry, and performed single-cell RNA sequencing (scRNA-seq) of tumor and normal tissues from 34 patients with GC.</p><p><strong>Results: </strong>We categorized 157 GC patients into LOW, MID, and HIGH groups based on their CD8 + T-cell infiltration. Overall survival was notably lower for the HIGH and LOW groups compared with the MID group. Our scRNA-seq data analysis showed that CD8 + T-cell activity markers in the HIGH group were expressed at lower levels than in normal tissue, but the T-cell-attracting chemokine CCL5 was expressed at a higher level. Notably, CD8 + T-cells in the HIGH group displayed lower PD1 expression and higher CTLA4 expression. TCR repertoire analysis using only Epstein-Barr virus-negative cases showed that CD8 + T-cell receptor clonality was lower in the HIGH group than in the MID group. Furthermore, in the HIGH group, the antigen-presenting capacity of type 1 conventional dendritic cells was lower, the immunosuppressive capacity of myeloid-derived suppressor cells was higher, and the expression of CTLA4 in regulatory T-cells was higher.</p><p><strong>Conclusion: </strong>The present data suggest that the infiltration of inactive CD8 + T-cells with low clonality is induced by chemotaxis in the HIGH group, possibly leading to a poor prognosis for patients with GC.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"211-227"},"PeriodicalIF":6.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic effects of dihydroartemisinin and cisplatin on inducing ferroptosis in gastric cancer through GPX4 inhibition.","authors":"Huina Wang, Chanchan Lu, Haihua Zhou, Xiaojun Zhao, Chuanjiang Huang, Zhiyi Cheng, Guiyuan Liu, Xiaolan You","doi":"10.1007/s10120-024-01574-7","DOIUrl":"10.1007/s10120-024-01574-7","url":null,"abstract":"<p><strong>Background: </strong>In the past several decades, cisplatin (DDP), in combination with other drugs, has been used as the mainstay chemotherapy drug for the treatment of gastric cancer (GC). However, the clinical application of DDP is restricted because of its toxic side effects, it is imperative to explore less toxic and more effective treatment strategies. Dihydroartemisinin (DHA) has been shown to exert potent anticancer effects through ferroptosis in multiple malignancies and has shown high efficacy and safety.</p><p><strong>Methods: </strong>Cell viability assay, live/dead staining assay, EDU proliferation assay, MitoTracker assay, BODIPY C11 assay and other cell assays in vitro were employed to observe DHA in combination with DDP inducing ferroptosis in GC. Subsequently, proteomic analysis integrated with database analysis and clinical sample detection were utilized to elucidate the mechanism of DHA inducing ferroptosis in GC both in vitro and in vivo.</p><p><strong>Results: </strong>In this study, we found that DHA combined with DDP can synergistically inhibit the proliferation, invasion and migration of GC cells and induce ferroptosis. Further studies have shown that DHA acts in combination with DDP to induce ferroptosis in GC cells by inhibiting GPX4 in vivo and in vitro.</p><p><strong>Conclusion: </strong>In summary, this study is the first to report that DHA and DDP synergically promote ferroptosis in GC cells, the combination of DDP and DHA is a promising strategy from the perspective of toxicity of DDP, which may be a promising therapeutic approach.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"187-210"},"PeriodicalIF":6.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of histologically poorly cohesive phenotype as a prognostic factor in patients with pStage II/III gastric cancer undergoing adjuvant chemotherapy.","authors":"Chikara Kunisaki, Sho Sato, Kohei Kasahara, Tsutomu Sato, Akikazu Yago, Yuko Tamura, Hiroki Kondo, Masanori Oshi, Takashi Kosaka, Hirotoshi Akiyama, Itaru Endo","doi":"10.1007/s10120-025-01599-6","DOIUrl":"https://doi.org/10.1007/s10120-025-01599-6","url":null,"abstract":"<p><strong>Background: </strong>Few studies have focussed on using histological phenotype to evaluate prognostic factors after adjuvant chemotherapy (AC) in patients with pStage II/III gastric cancer. We evaluated the impact of histological type based on the World Health Organization classification.</p><p><strong>Methods: </strong>Overall, 348 patients with pStage II/III advanced gastric cancer undergoing R0 gastrectomy without neoadjuvant chemotherapy were included. Of these, 143 underwent AC. Univariate and multivariate analyses for prognostic factors of relapse-free survival (RFS) and overall survival (OS) were performed in all patients and patients receiving AC. Moreover, long-term survivals were compared by histological phenotype between patients with and without AC.</p><p><strong>Results: </strong>Multivariate analysis in all patients revealed that histologically poorly cohesive carcinoma with not otherwise specified and signet ring cell subtype (PCC-NOS/SRC) and pN 2/3 independently and adversely affected RFS. Alternatively, male sex, poor PS and pN 2/3 adversely affected OS. In multivariate analysis of patients receiving AC, longer tumour size (≥ 80 mm), histologically PCC-NOS/SRC phenotype and pN 3 independently influenced RFS. Multivariate analysis in this population for OS revealed that pN 3 and poor postoperative immune-nutritional status significantly induced worse OS. Comparison of RFS and OS by histological phenotype between patients with and without AC showed that AC had no efficacy for improving long-term survivals in histologically PCC phenotype.</p><p><strong>Conclusions: </strong>Histologically PCC phenotype by WHO classification, particularly PCC-NOS/SRC phenotypes, showed poor long-term RFS even after AC in patients with pStage II and III gastric cancer. An effective chemotherapeutic regimen needs to be developed for this specific subtype of gastric cancer.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Robotic and laparoscopic gastrectomy for gastric cancer: comparative insights into perioperative performance and three-year survival outcomes.","authors":"Yuki Ushimaru, Takeshi Omori, Kazuyoshi Yamamoto, Yoshitomo Yanagimoto, Yasunori Masuike, Norihiro Matsuura, Takahito Sugase, Takashi Kanemura, Ryota Mori, Masatoshi Kitakaze, Masataka Amisaki, Masahiko Kubo, Yousuke Mukai, Hisateru Komatsu, Toshinori Sueda, Yoshinori Kagawa, Hiroshi Wada, Kunihito Gotoh, Masayoshi Yasui, Hiroshi Miyata","doi":"10.1007/s10120-025-01601-1","DOIUrl":"https://doi.org/10.1007/s10120-025-01601-1","url":null,"abstract":"<p><strong>Background: </strong>The primary treatment for gastric cancer (GC) is surgical resection, particularly for locally advanced cases. While laparoscopic gastrectomy (LG) has shown short- and long-term benefits, robotic gastrectomy (RG) offers enhanced precision and may lead to better outcomes, especially in advanced-stage disease.</p><p><strong>Methods: </strong>This retrospective study analyzed data from 1538 patients with pathological Stage I-III GC who underwent RG or LG between 2014 and 2021. Propensity score matching created 466 matched pairs. Perioperative outcomes, 3 year overall survival (OS), 3 year recurrence-free survival (RFS), and recurrence patterns were compared between RG and LG.</p><p><strong>Results: </strong>RG demonstrated significantly shorter operative time (235.5 vs. 242.5 min, p = 0.001), less blood loss (19.1 vs. 33.4 ml, p < 0.001), and shorter hospital stay (7.9 vs. 9.7 days, p < 0.001). Overall complications did not differ significantly (p = 0.183), but RG had lower rates of anastomotic leakage (p = 0.045) and pancreatic fistula (p = 0.024). No significant differences in OS were observed in the overall cohort or by stage. Similarly, RFS showed no significant differences in the overall cohort (3 year RFS: RG 86.81% vs. LG 83.04%, p = 0.1347). By stage, no differences were found in stage I or II, but in stage III, RG showed better 3 year RFS (67.52% vs. 52.97%, p = 0.0424). RG also had lower recurrence rates (9.0% vs. 14.8%, p = 0.0061), with fewer liver (p = 0.0069) and lymph node metastases (p = 0.0223).</p><p><strong>Conclusion: </strong>RG demonstrated superior short-term outcomes and comparable three-year OS to laparoscopic gastrectomy, with improved three-year RFS and reduced recurrence in Stage III, likely facilitated by earlier adjuvant chemotherapy initiation.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of ADAMTS14 genetic polymorphisms and its function on susceptibility to and prognosis of gastric cancer in a Chinese Han population.","authors":"Pengyu Li, Jiacheng Dong, Yuan Li, Jiang Yan, Jiawei Wang, Shuqing Cao, Wei Cao, Xinyu Zhao, Ao Xue, Zekuan Xu, Li Yang","doi":"10.1007/s10120-025-01598-7","DOIUrl":"https://doi.org/10.1007/s10120-025-01598-7","url":null,"abstract":"<p><strong>Background: </strong>Single nucleotide polymorphisms (SNPs) are associated with various diseases, including gastric cancer. The ADAMTS14 gene is linked to multiple types of cancer. However, the relationship between ADAMTS14 and its genetic polymorphisms with susceptibility to gastric cancer (GC) and prognosis remains unclear.</p><p><strong>Methods: </strong>A case-control study was conducted involving 855 patients diagnosed with gastric cancer (GC) and an equal number of cancer-free controls. Following rigorous statistical analysis, molecular experiments were performed to elucidate the functional significance of the SNPs in the context of GC.</p><p><strong>Results: </strong>ADAMTS14 rs3740440 (OR = 1.45, p = 0.014) shows a significant association with increased GC risk, while rs11572 (OR = 0.42, p < 0.001) is associated with protection against GC. Moreover, patients with the (CG + GG) genotype of rs3740440 exhibit a poor prognosis (HR = 1.68, p = 0.007). Mechanistically, luciferase reporter assays revealed that the G allele of rs3740440 disrupts the binding of hsa-miR-4294 and hsa-miR-3198 to the 3' untranslated region (3' UTR) of ADAMTS14, leading to increased expression of ADAMTS14 and the promotion of malignant behaviors in GC cells.</p><p><strong>Conclusions: </strong>Our findings underscore the significant role of ADAMTS14 SNPs in both the risk and prognosis of gastric cancer (GC), providing valuable insights into the underlying molecular mechanisms. Specifically, rs3740440 disrupts the interaction between ADAMTS14 and miRNA, resulting in increased expression of ADAMTS14. This heightened expression enhances its malignant biologic behaviors, indicating that rs3740440 could be a potential predictive marker for gastric cancer risk and prognosis.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial organization of B lymphocytes and prognosis prediction in patients with gastric cancer.","authors":"Ryan Yong Kiat Tay, Manavi Sachdeva, Haoran Ma, Young-Woo Kim, Myeong-Cherl Kook, Hyunki Kim, Jae-Ho Cheong, Lindsay C Hewitt, Günter Schmidt, Takaki Yoshikawa, Takashi Oshima, Tomio Arai, Supriya Srivastava, Ming Teh, Xuewen Ong, Su Ting Tay, Taotao Sheng, Joseph J Zhao, Patrick Tan, Heike I Grabsch, Raghav Sundar","doi":"10.1007/s10120-025-01593-y","DOIUrl":"https://doi.org/10.1007/s10120-025-01593-y","url":null,"abstract":"<p><strong>Background: </strong>Within the tumor microenvironment (TME), the association of B lymphocytes (B cells) with prognosis and therapy response in gastric cancer (GC) remains poorly characterized. We investigated the predictive and prognostic value of B cells, including their spatial organization within the TME, in one of the largest multi-cohort studies to date.</p><p><strong>Methods: </strong>Using CD20 immunohistochemistry, we evaluated B cell density in resection specimens from 977 patients with resectable GC across three cohorts, including the randomized phase III Korean CLASSIC trial. The relationship between CD20 density, clinicopathological characteristics, and overall survival (OS) was analyzed. Digital spatial profiling of 1063 regions of interest from 15 patients was performed to characterize B cell distribution within different regions of interest (ROIs) using the NanoString GeoMx platform.</p><p><strong>Results: </strong>CD20 density was significantly higher in diffuse-type GC compared to intestinal-type (p = 0.000012). Patients with CD20-low diffuse-type GC had the shortest OS in the CLASSIC trial (median OS: 49 vs 62 months, HR: 1.9, 95% CI: 1.2-3.0, p = 0.003) and in a Japanese cohort (median OS: 49 vs 67 months, HR: 2.2, 95% CI: 1.2-4.0, p = 0.011). This survival difference was not seen in patients treated with adjuvant chemotherapy (median OS: 62 vs 63 months, HR: 1.8, 95% CI: 0.88-3.5, p = 0.108). Spatial profiling revealed significant B cell enrichment within tumor ROIs compared to the stroma, particularly in diffuse-type GC.</p><p><strong>Conclusions: </strong>Low CD20 positivity, especially in diffuse-type GC, is linked to poor prognosis and may identify patients who could benefit from chemotherapy. These findings underscore the role of B cells in GC.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}