Gastric Cancer最新文献

{"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}

{"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":"https://doi.org/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":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-17","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":"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":"https://doi.org/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":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-17","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}

{"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":"https://doi.org/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":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lenvatinib suppress FGF19-FGFR4 signaling to enhance antitumor immune response in gastric cancer.","authors":"Yuya Maruyama, Motonobu Saito, Shotaro Nakajima, Katsuharu Saito, Hiroya Suzuki, Ryo Kanoda, Hirokazu Okayama, Hiroyuki Hanayama, Wataru Sakamoto, Zenichiro Saze, Tomoyuki Momma, Kosaku Mimura, Akiteru Goto, Koji Kono","doi":"10.1007/s10120-025-01596-9","DOIUrl":"https://doi.org/10.1007/s10120-025-01596-9","url":null,"abstract":"<p><strong>Background: </strong>Fibroblast growth factor receptor (FGFR) 4 is overexpressed in gastric cancer (GC) and is a potential therapeutic target for GC. Since the FGF/FGFR signaling is involved in tumor microenvironment inducing the formation of an immunosuppression, lenvatinib is expected to inhibit FGFR4 leading to reduced tumor PD-L1 levels and regulatory T cell (Treg) infiltration, improving pembrolizumab efficacy. This study explored the background of the molecular mechanisms underlying the therapeutic efficacy of lenvatinib plus pembrolizumab.</p><p><strong>Methods: </strong>Expression of FGFR4 and its specific ligand FGF19 was assessed by immunohistochemical staining and clinicopathological relevance was also examined. The effect of lenvatinib on FGF19-FGFR4 signaling was evaluated using cellular experiments. Lastly, the expression of FGFR4 on Treg cells was evaluated by immunostaining and flow cytometry. The Cancer Genome Atlas cBioPortal and Gene Expression Omnibus microarray databases were accessed to support these results.</p><p><strong>Results: </strong>High FGFR4 expression was associated with histological type and venous invasion and predominantly detected in human epidermal growth factor receptor 2 and Epstein-Barr virus-positive GC. Bioinformatics data suggested that FGF19-FGFR4 signaling was activated in GC, and cellular experiments showed that lenvatinib reduced FGFR4 and PD-L1 expression in GC cells. Results of integrating various analyses suggested that FGFR4 did not seem to be enough expressed on Treg cells in GC.</p><p><strong>Conclusions: </strong>The FGF19-FGFR4 signaling has a pivotal role in gastric tumorigenesis and may be involved in immunosuppression through PD-L1 modification. But, lenvatinib may not regulate immune editing by directly inhibiting FGFR4 on Treg cells.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414068","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":"Multiple metachronous foveolar-type gastric adenomas in a Helicobacter pylori-naïve patient with long-term use of a proton pump inhibitor: a case report.","authors":"Yoichi Miyaoka, Kotaro Shibagaki, Ryoji Kushima, Taisuke Omachi, Takanobu Hino, Aya Fujiwara, Kousuke Tsukano, Sayaka Ogawa, Satoshi Yamanouchi, Masaki Tanaka, Tatsuya Miyake, Hirofumi Fujishiro, Naruaki Kohge, Hideyuki Ohnuma, Norihisa Ishimura, Tsuyoshi Mishiro, Shunji Ishihara","doi":"10.1007/s10120-025-01595-w","DOIUrl":"https://doi.org/10.1007/s10120-025-01595-w","url":null,"abstract":"<p><p>A 69-year-old man undergoing long-term administration of a proton-pump inhibitor (PPI) underwent upper endoscopy, which found a small, whitish, flat lesion in the fundic gland (oxyntic) mucosa. The patient had never received treatment for Helicobacter pylori (Hp) infection, and diagnostic testing for Hp was negative, suggesting an Hp-naïve status. Two years later, the lesion appeared markedly enlarged and was endoscopically resected. Histological examination revealed a low-grade foveolar-type gastric adenoma (FGA), predominantly expressing MUC5AC by immunohistochemistry. Two years later, while PPI therapy was continued, three new flat lesions were found. These were endoscopically resected and histologically diagnosed as low-grade FGAs as before, suggesting that multiple metachronous tumors had developed in a short period of time during long-term PPI administration. A KRAS mutation and a CTNNB1 mutation were identified in the tumor. To our best knowledge, this is the first report of potentially PPI-associated multiple metachronous FGAs in an Hp-naïve patient. Here we report a case of multiple foveolar-type gastric adenomas with rapid metachronous recurrences during long-term use of a proton pump inhibitor in Helicobacter pylori-naïve patient.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407085","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}