{"title":"Investigating the role of inflammatory cytokines in mediating the effect of gut microbiota on gastrointestinal cancers: a mendelian randomization study.","authors":"Wen-Tao Liu, Xin-Wen Hu, Yan-Ni Choy, Wei Lai, He-Yang Xu, Yu-Jie Zeng, Qiu-Sheng Lan, Lu Liu, Rong-Bin Yue, Zhong-Hua Chu","doi":"10.1007/s10120-025-01587-w","DOIUrl":"10.1007/s10120-025-01587-w","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study is to explore the causal relationship between gut microbiota and gastrointestinal (GI) cancers and to investigate the potential mediating factors influencing the development of GI cancers.</p><p><strong>Methods: </strong>Using data from genome-wide association studies (GWAS), we employed two-sample Mendelian randomization (TSMR) to explore the relationship among gut microbiota, inflammatory cytokines and GI cancers. Subsequently, a multivariable Mendelian randomization (MVMR) analysis was meticulously conducted to perform a mediation analysis, thereby estimating the proportion of mediation effects conferred by inflammatory cytokines.</p><p><strong>Results: </strong>TSMR analysis established a causal relationship between 23 gut microbiota taxa and 11 inflammatory cytokines with GI cancers. Specifically, 7 gut microbiota taxa were associated with an increased risk of gastric cancer (GC), 6 with small intestine cancer, and 10 with colorectal cancer (CRC). Among the inflammatory cytokines, 4 were linked to GC risk, 3 to small intestine cancer, and to CRC. Mediation analysis further indicatedthat tumor necrosis factor ligand superfamily member 12 (TNFSF12) mediated 9.703% (95% CI 0.108%~15.891%) of the total effect of genus Ruminiclostridium9 on GC.</p><p><strong>Conclusion: </strong>Our findings support a causal relationship between gut microbiota, inflammatory cytokines, and GI cancers. These biomarkers provide new insights into the mechanisms underlying GI cancers and have the potential to improve strategies forprevention, diagnosis, and treatment.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"442-454"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440601","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":"Appetite-preserving gastrectomy (APG) for esophagogastric junction cancer: preserving the residual stomach as an endocrine organ.","authors":"Naoki Hiki, Tadashi Higuchi, Koshi Kumagai, Kota Okuno, Hiroyuki Minoura, Yumi Sato, Shohei Fujita, Hiroki Harada, Motohiro Chuman, Marie Washio, Mikiko Sakuraya, Masahiro Niihara, Yusuke Kumamoto, Takeshi Naitoh, Keishi Yamashita","doi":"10.1007/s10120-025-01603-z","DOIUrl":"10.1007/s10120-025-01603-z","url":null,"abstract":"<p><strong>Background: </strong>Loss of appetite following gastric cancer surgery, particularly total gastrectomy, significantly impacts patient quality of life due to the removal of the ghrelin-secreting region. We developed appetite-preserving gastrectomy (APG), a modified total gastrectomy that preserves this region.</p><p><strong>Methods: </strong>Ten consecutive patients with esophagogastric junction cancer who were indicated for total gastrectomy and underwent APG between April 2023 and April 2024 were evaluated for early surgical outcomes, appetite, and changes in weight and body composition.</p><p><strong>Results: </strong>There were no postoperative complications of grade II or higher (Clavien-Dindo classification). Appetite, assessed using the Simplified Nutritional Appetite Questionnaire, showed no significant impairment at 3 months (14.5 points, P = 0.82) and 6 months (15 points, P = 0.44) postoperatively compared with preoperative values. Oral calorie intake was maintained at 3 months (1675 kcal, P = 0.97) and 6 months (1675 kcal, P = 0.22) postoperatively compared with preoperative levels. The patients' body weight decreased by 9.2% at 6 months postoperatively compared with preoperative values, but their lean body mass remained stable. Although a significant decrease in the blood Ghrelin levels was observed postoperatively, 53% and 60.4% of the preoperative levels was maintained at one month and 6 months, respectively.</p><p><strong>Conclusions: </strong>APG is a safe procedure that preserves the residual stomach as an endocrine organ, maintains ghrelin secretion and appetite, and prevents muscle loss. However, further trials are required to compare the efficacy of APG with total gastrectomy in preventing postoperative appetite loss.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"527-536"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656911","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}
Gastric CancerPub Date : 2025-05-01Epub Date: 2025-03-01DOI: 10.1007/s10120-025-01602-0
Chao He, Zheng Zhou, Yan Yang, Songting Zhu, Haiyong Wang, Lisong Teng
{"title":"FERMT2 drives anoikis resistance and peritoneal metastasis by enhancing extracellular matrix deposition in gastric cancer.","authors":"Chao He, Zheng Zhou, Yan Yang, Songting Zhu, Haiyong Wang, Lisong Teng","doi":"10.1007/s10120-025-01602-0","DOIUrl":"10.1007/s10120-025-01602-0","url":null,"abstract":"<p><p>Peritoneal metastasis is a critical step in the progression of gastric cancer (GC), yet its underlying mechanisms remain poorly understood. Here, we identify FERMT2, a member of the Kindlin protein family, as a key regulator of anoikis resistance (AR) and peritoneal metastasis in GC. FERMT2 expression increases in a suspension-time-dependent manner and is associated with higher pathological grade, advanced clinical stage, and poorer prognosis. Functional studies in vitro and in vivo demonstrate that FERMT2 promotes AR and facilitates peritoneal metastasis. Mechanistically, FERMT2 suppresses the ubiquitination of SOX2, thereby enhancing its stability and up-regulating FN1 transcription. Furthermore, we report that TGFβ-RI expression also increases in a suspension-time-dependent manner, forming a positive feedback loop with FERMT2 via TGFβ-1/TGFβ-RI signaling. This feedback loop drives extracellular fibronectin matrix deposition, strengthens cell-matrix interactions, and supports AR. These findings establish FERMT2 as a pivotal mediator of peritoneal metastasis in GC, offering insights into its potential as a therapeutic target.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"409-421"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536968","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":"Clinicopathological significance of JAK2, STAT3, and STAT4 expression in patients with gastric solid-type poorly differentiated adenocarcinoma: a retrospective study.","authors":"Shinya Umekita, Daisuke Kiyozawa, Hitoshi Honma, Kenichi Kohashi, Yoshiaki Taniguchi, Shinichiro Kawatoko, Taisuke Sasaki, Eikichi Ihara, Eiji Oki, Masafumi Nakamura, Yoshihiro Ogawa, Yoshinao Oda","doi":"10.1007/s10120-025-01589-8","DOIUrl":"10.1007/s10120-025-01589-8","url":null,"abstract":"<p><strong>Background: </strong>The role of janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling remains unclear in gastric solid-type poorly differentiated adenocarcinoma. The present study investigates the clinicopathological significance of JAK2, STAT3, and STAT4 expression in solid-type poorly differentiated adenocarcinoma.</p><p><strong>Methods: </strong>We retrospectively enrolled 102 participants with primary solid-type poorly differentiated adenocarcinoma. We categorized participants according to deficient or proficient mismatch repair status (46 and 56 participants, respectively). Expression of phosphorylated JAK2 (pJAK2), phosphorylated STAT3 (pSTAT3), and STAT4 were analyzed via immunohistochemistry. We analyzed differences in protein expression in relation to mismatch repair status, and associations of high/low protein expression with clinicopathological characteristics and prognoses.</p><p><strong>Results: </strong>Deficient mismatch repair was found to be associated with high pJAK2 (p = 0.038) and STAT4 (p = 0.023) expression in contrast to proficient mismatch repair. Log-rank analysis revealed high pSTAT3 and low STAT4 expression to be significantly correlated with reduced overall survival (p = 0.001). Multivariate analysis revealed high pSTAT3 and low STAT4 expression to be independent indicators of unfavorable prognosis (hazard ratio = 2.751, p = 0.030), as was proficient mismatch repair status (hazard ratio = 3.819, p = 0.012).</p><p><strong>Conclusions: </strong>High expression of pJAK2 and STAT4 is more frequent in deficient compared with proficient mismatch repair in solid-type poorly differentiated adenocarcinoma. High pSTAT3 and low STAT4 expression could be a useful prognostic indicator in solid-type poorly differentiated adenocarcinoma.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"455-464"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440571","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}
Gastric CancerPub Date : 2025-05-01Epub Date: 2025-02-24DOI: 10.1007/s10120-025-01598-7
Pengyu Li, Jiacheng Dong, Yuan Li, Jiang Yan, Jiawei Wang, Shuqing Cao, Wei Cao, Xinyu Zhao, Ao Xue, Zekuan Xu, Li Yang
{"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":"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":"326-343"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","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}
Gastric CancerPub Date : 2025-05-01Epub Date: 2025-02-10DOI: 10.1007/s10120-025-01594-x
Likun Zan, Xin Zhang, Lulu Shen, Qi Zhao, Dongfeng Tan, Xiao Peng, Yi Jia, Jiawen Li, Jing Liu, Jiaqi Zhao, Ning Gao, Peng Bu, Yanfeng Xi
{"title":"Genomic landscape and potential therapeutic targets in alpha-fetoprotein-producing gastric cancer.","authors":"Likun Zan, Xin Zhang, Lulu Shen, Qi Zhao, Dongfeng Tan, Xiao Peng, Yi Jia, Jiawen Li, Jing Liu, Jiaqi Zhao, Ning Gao, Peng Bu, Yanfeng Xi","doi":"10.1007/s10120-025-01594-x","DOIUrl":"10.1007/s10120-025-01594-x","url":null,"abstract":"<p><p>Alpha-fetoprotein-producing gastric carcinoma (AFPGC) is a rare and aggressive subtype of gastric cancer (GC). A comprehensive analysis of clinicopathological features, immunophenotypes, molecular characteristics, and survival in AFPGC contributes to identifying potential therapeutic targets and developing new strategies to manage this disease. A retrospective cohort study was conducted at Shanxi Cancer Hospital from January 2018 to December 2020, involving patients diagnosed with GC and elevated AFP serum levels. Among these, 91 patients underwent immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS) to reveal the immunophenotypic and molecular characteristics of AFPGC. We found that AFPGC is more common in males and primarily occurs in the cardia and antrum of the stomach. A panel of IHC markers including AFP, GPC3, SALL4, CD10, CDX-2, and ATBF1 can be used for the diagnosis and differentiating AFPGC. NGS analysis revealed that TP53 hypermutation was the most frequent molecular event associated with AFPGC. The altered signaling pathways included disease signal transduction, receptor tyrosine kinase signaling and intracellular second messenger signaling pathways. The cumulative incidence of 21 genes, based on the evidence of clinical actionability in the OncoKB, was found to be 59.34%. Among these genes, CCNE1, ERBB2, and EGFR were the most frequently observed. This underscores the potential benefit of targeted therapy for patients with AFPGC. Furthermore, LRP1B and ARID1A have been identified as prognostic factors associated with overall survival (OS) and disease-free survival (DFS), respectively. Our results aim to improve AFPGC diagnosis by identifying potential therapeutic targets and prognostic factors, which could help facilitate the development of new treatment strategies.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"372-383"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382282","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}
Gastric CancerPub Date : 2025-05-01Epub Date: 2025-02-17DOI: 10.1007/s10120-025-01588-9
Mary E Booth, Henry M Wood, Mark A Travis, Phil Quirke, Heike I Grabsch
{"title":"The relationship between the gastric cancer microbiome and clinicopathological factors: a metagenomic investigation from the 100,000 genomes project and The Cancer Genome Atlas.","authors":"Mary E Booth, Henry M Wood, Mark A Travis, Phil Quirke, Heike I Grabsch","doi":"10.1007/s10120-025-01588-9","DOIUrl":"10.1007/s10120-025-01588-9","url":null,"abstract":"<p><strong>Background: </strong>Findings from previous gastric cancer microbiome studies have been conflicting, potentially due to patient and/or tumor heterogeneity. The intratumoral gastric cancer microbiome and its relationship with clinicopathological variables have not yet been characterized in detail. We hypothesized that variation in gastric cancer microbial abundance, alpha diversity, and composition is related to clinicopathological characteristics.</p><p><strong>Methods: </strong>Metagenomic analysis of 529 GC samples was performed, including whole exome sequencing data from The Cancer Genome Atlas (TCGA) and whole genome sequencing data from the 100,000 Genomes Project. Microbial abundance, alpha diversity, and composition were compared across patient age, sex, tumor location, geographic origin, pathological depth of invasion, pathological lymph node status, histological phenotype, microsatellite instability status, and TCGA molecular subtype.</p><p><strong>Results: </strong>Gastric cancer microbiomes resembled previous results, with Prevotella, Selenomonas, Stomatobaculum, Streptococcus, Lactobacillus, and Lachnospiraceae commonly seen across both cohorts. Within the TCGA cohort, microbial abundance and alpha diversity were greater in gastric cancers with microsatellite instability, lower pathological depth of invasion, intestinal-type histology, and those originating from Asia. Microsatellite instability status was associated with microbiome composition in both cohorts. Sex and pathological depth of invasion were associated with microbiome composition in the TCGA cohort.</p><p><strong>Conclusion: </strong>The intratumoral gastric cancer microbiome appears to differ according to clinicopathological factors. Certain clinicopathological factors associated with favourable outcomes in gastric cancer were observed to be associated with greater microbial abundance and diversity. This highlights the need for further work to understand the underlying biological mechanisms behind the observed microbiome differences and their potential clinical and therapeutic impact.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"358-371"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440605","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}
Gastric CancerPub Date : 2025-05-01Epub Date: 2025-02-07DOI: 10.1007/s10120-025-01584-z
Peng Zhang, Changjuan Tao, Hanfei Xie, Liu Yang, Ye Lu, Yun Xi, Shili Yao, Li Yuan, Peng Guo, Xiangdong Cheng
{"title":"Identification of CD66c as a potential target in gastroesophageal junction cancer for antibody-drug conjugate development.","authors":"Peng Zhang, Changjuan Tao, Hanfei Xie, Liu Yang, Ye Lu, Yun Xi, Shili Yao, Li Yuan, Peng Guo, Xiangdong Cheng","doi":"10.1007/s10120-025-01584-z","DOIUrl":"10.1007/s10120-025-01584-z","url":null,"abstract":"<p><strong>Background: </strong>Gastroesophageal junction (GEJ) cancer exhibits unique biological characteristics and currently lacks specific targeted therapies. Given the clinical efficacy of antibody-drug conjugates (ADCs) in solid tumor treatment, we aimed to identify a novel ADC target and suitable payload for GEJ-targeted therapy.</p><p><strong>Methods: </strong>In this study, we conducted bioinformatic analyses of multi-omics data, including transcriptomics, proteomics, and phosphoproteomics, to identify CD66c as a promising ADC target for GEJ cancer. We then engineered a CD66c-directed antibody-drug conjugate (CD66c-DXd) incorporating a GGFG linker. The preclinical efficacy of CD66c-DXd was determined in multi GEJ xenograft models.</p><p><strong>Results: </strong>Proteomic analyses of 103 cases of GEJ cancer revealed that CD66c expression was significantly higher in tumoral tissues compared to normal tissues. Proteomic and phosphoproteomic analyses identified deruxtecan (DXd) as a potentially potent payload for ADCs targeting GEJ cancer. Furthermore, high CD66c expression in GEJ was associated with a significantly lower proportion of plasma cells. The drug-to-antibody ratio (DAR) of CD66c-DXd was determined to be 3.6. CD66c-DXd effectively and selectively ablated multiple human GEJ cell lines (OE-19, OE33 and SK-GT-4) without affecting non-malignant cells (GES-1) in vitro. Eventually, CD66c-DXd mediated potent and durable tumor regression in vivo with excellent safety profiles.</p><p><strong>Conclusions: </strong>This preclinical study provides a strong rationale for the further development of CD66c-DXd as promising therapeutic candidates to treat advanced GEJ cancer. Additionally, the study demonstrates the robustness of the multi-omics data in identifying novel potential ADC targets and payloads.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"422-441"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363943","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}
Gastric CancerPub Date : 2025-05-01Epub Date: 2025-02-19DOI: 10.1007/s10120-025-01593-y
Ryan Yong Kiat Tay, Manavi Sachdeva, Haoran Ma, Young-Woo Kim, Myeong-Cherl Kook, Hyunki Kim, Jae-Ho Cheong, Lindsay C Hewitt, Katharina Nekolla, 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
{"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, Katharina Nekolla, 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":"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":"384-396"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993452/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Differential impact of frailty on surgical and non-surgical site complications in patients with gastric cancer undergoing gastrectomy.","authors":"Katsunobu Sakurai, Naoshi Kubo, Tatsuro Tamura, Tsuyoshi Hasegawa, Yutaka Tamamori, Junya Nishimura, Yasuhito Iseki, Takafumi Nishii, Toru Inoue, Masakazu Yashiro, Yukio Nishiguchi, Tsubasa Bito, Kiyoshi Maeda","doi":"10.1007/s10120-025-01590-1","DOIUrl":"10.1007/s10120-025-01590-1","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to determine the differential impact of frailty on surgical site complications (SSCs) and non-surgical site complications (non-SSCs) in gastric cancer (GC) patients undergoing gastrectomy.</p><p><strong>Methods: </strong>In this study, frailty was assessed preoperatively using a frailty index (FI) in 395 patients scheduled for gastrectomy for GC between January 2016 and December 2023. Patients were divided into two groups (high FI vs. low FI) to examine the impact of frailty on SSC and non-SSC.</p><p><strong>Results: </strong>Overall complication and non-SSC rates were significantly higher in the high FI group, but the two groups had similar rates of SSC. In multivariate analysis, high FI, high BMI, and male were independent risk factors for non-SSC. The incidence of non-SSC was 0% in patients with no applicable risk factors, 3.6% in patients with one applicable risk factor, 13.0% in patients with two applicable risk factors, and 37.1% in patients with all three risk factors (Cochran-Armitage trend test, p < 0.001). The area under the curve (AUC) of the risk prediction model using these three variables to predict non-SSC was 0.760.</p><p><strong>Conclusions: </strong>High FI was an independent risk factor for non-SSC in patients undergoing gastrectomy for GC. Our developed non-SSC risk model combining FI, BMI, and sex effectively identifies individuals at increased risk for non-SSC in GC patients.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"501-513"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058787","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}