Gastric Cancer最新文献

{"title":"Long-term prognosis of mixed histological-type gastric cancers cured by endoscopic resection: a multicenter prospective cohort study.","authors":"Yusuke Horiuchi, Toshiaki Hirasawa, Haruhisa Suzuki, Kohei Takizawa, Yoji Takeuchi, Kenji Ishido, Shu Hoteya, Tomonori Yano, Shinji Tanaka, Yosuke Toya, Masahiro Nakagawa, Tetsuya Yoshizaki, Naohiro Yoshida, Kingo Hirasawa, Mitsuru Matsuda, Hironori Yamamoto, Shigeto Koizumi, Shinichiro Hori, Masahiro Tajika, Takuto Hikichi, Kenshi Yao, Taichi Shimazu, Hiroyuki Ono, Satoshi Tanabe, Hitoshi Kondo, Hiroyasu Iishi, Motoki Ninomiya, Ichiro Oda","doi":"10.1007/s10120-025-01651-5","DOIUrl":"https://doi.org/10.1007/s10120-025-01651-5","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer is divided into differentiated and undifferentiated types and sometimes exhibits mixed histology. However, the risk of gastric cancer-related death after curative endoscopic resection for mixed histology remains unknown. This study evaluated the long-term prognosis of mixed histological type gastric cancers treated with endoscopic resection.</p><p><strong>Methods: </strong>Data from a Japanese multicenter prospective cohort study were analyzed. Patients with single gastric cancer lesions who underwent curative endoscopic resection were included and divided into those with pure or mixed histological types. Patients with both types of gastric cancer were compared in terms of 5-year overall survival and 5-year disease-specific survival related to primary gastric cancers.</p><p><strong>Results: </strong>Pure histological type was observed in 6434 patients with 6434 lesions, and mixed histological type was observed in 161 patients with 161 lesions. Overall survival was not significantly different between patients with both types (p = 0.415). The 5-year disease-specific survival was lower in patients with mixed histological type than in those with pure histological type (p = 0.003). After stratification by curative endoscopic resection criteria, in cases of pT1a/M, differentiated-type dominance, tumor size ≤ 3 cm with ulcerative findings, no lymphovascular invasion, and R0 resection, the 5-year disease-specific survival was significantly lower in patients with mixed histological type than in those with pure type (p < 0.001).</p><p><strong>Conclusions: </strong>The long-term prognosis in cured cases, including those with mixed histological type, was favorable. Stratification analysis showed that mixed histological types with ulcers were more likely to cause primary gastric cancer-related death than pure histological type and might need more careful surveillance.</p><p><strong>Clinical trial registration: </strong>UMIN Clinical Trial Registry, UMIN000005871.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768610","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":"Neoantigen mRNA vaccines induce progenitor-exhausted T cells that support anti-PD-1 therapy in gastric cancer with peritoneal metastasis.","authors":"Koji Nagaoka, Hideyuki Nakanishi, Hiroki Tanaka, Jessica Anindita, Takeshi Kawamura, Toshiya Tanaka, Takefumi Yamashita, Akihiro Kuroda, Sachiyo Nomura, Hidetaka Akita, Keiji Itaka, Tatsuhiko Kodama, Kazuhiro Kakimi","doi":"10.1007/s10120-025-01640-8","DOIUrl":"https://doi.org/10.1007/s10120-025-01640-8","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer with peritoneal metastasis is associated with a poor prognosis. Current treatments, including the first-line therapy of combination chemotherapy with nivolumab for advanced recurrent gastric cancer, have shown limited efficacy against peritoneal dissemination. In this study, we evaluated neoantigen (neoAg)-mRNA lipid nanoparticle (LNP) as a potential agent in combination with anti-PD-1 therapy, focusing on its effects on neoAg-specific CD8⁺ T cell responses and antitumor efficacy in a murine gastric cancer model.</p><p><strong>Methods: </strong>The mRNA, comprising a tandem minigene encoding three neoAgs identified from the murine gastric cancer YTN16 cell line, was synthesized by in vitro transcription and encapsulated within LNPs. NeoAg-specific CD8⁺ T cells in the spleens and tumors were assessed by flow cytometry. The antitumor efficacy of the neoAg-mRNA-LNP vaccine, alone or in combination with anti-PD-1 antibody, was evaluated in both subcutaneous and peritoneal metastasis models of YTN16.</p><p><strong>Results: </strong>The neoAg-mRNA-LNP vaccine induced significantly higher frequencies of neoAg-specific CD8⁺ T cells than the neoAg-dendritic cell vaccine, confirming its enhanced immunogenicity. NeoAg-mRNA-LNP vaccination led to robust tumor regression, achieving complete eradication in all treated mice, especially when combined with anti-PD-1 therapy. This effect was associated with an increase in neoAg-specific progenitor-exhausted and intermediate-exhausted CD8⁺ T cells. In a peritoneal metastasis model, neoAg-mRNA-LNP monotherapy prevented peritoneal dissemination when administered prophylactically, and combination therapy with anti-PD-1 effectively suppressed tumor growth in a therapeutic setting.</p><p><strong>Conclusions: </strong>NeoAg-mRNA-LNP vaccines elicit potent neoAg-specific CD8⁺ T cell responses and show enhanced antitumor efficacy with anti-PD-1 therapy in gastric cancer with peritoneal metastasis.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753198","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":"Early stage gastric cancer with unusual sarcomatous component and no recurrence after endoscopic submucosal dissection: a case report.","authors":"Kohei Shigeta, Yoichi Yamamoto, Tadakazu Shimoda, Takashi Sugino, Hiroyuki Ono","doi":"10.1007/s10120-025-01650-6","DOIUrl":"https://doi.org/10.1007/s10120-025-01650-6","url":null,"abstract":"<p><p>Gastric cancer with sarcomatous changes is relatively rare and often detected at an advanced stage. We report the case of an 82-year-old man with early stage gastric cancer exhibiting an unusual morphology with a polypoid growth of a sarcomatous component arising from a flat area of a well-differentiated adenocarcinoma. He achieved mid-term remission after endoscopic submucosal dissection (ESD). Upon admission, upper gastrointestinal endoscopy revealed a 60-mm flat elevated lesion with a nodule; no lymph node or distant metastasis was noted. He was diagnosed with early stage gastric cancer and underwent ESD. Pathological examination of the nodule revealed carcinomatous cells transitioning to atypical spindle cells and sarcomatous changes, suggesting that the sarcomatous component originated from a gastric-type adenocarcinoma. There was no local recurrence or metastasis at 21 months post-ESD. This is the first report of a case of early stage gastric cancer with a sarcomatous change that achieved mid-term outcome after ESD.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753197","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":"Predictive value of homologous recombination-related gene mutations in survival outcomes of first-line nivolumab plus chemotherapy for gastric cancer.","authors":"Yuna Lee, Hyung-Don Kim, Sun Young Lee, Hyungeun Lee, Jaewon Hyung, Meesun Moon, Jinho Shin, Young Soo Park, Tae Won Kim, Min-Hee Ryu","doi":"10.1007/s10120-025-01648-0","DOIUrl":"https://doi.org/10.1007/s10120-025-01648-0","url":null,"abstract":"<p><strong>Background: </strong>Homologous recombination repair (HRR) gene mutations contribute to genomic instability. However, their clinical value in immune checkpoint inhibitor (ICI)-based treatments in gastric cancer remains unclear. Therefore, this study aims to investigate the efficacy of nivolumab plus chemotherapy according to the HRR mutation status in patients with advanced gastric cancer.</p><p><strong>Methods: </strong>This single-center study included patients with gastric cancer with available panel sequencing results who were treated with first-line nivolumab plus chemotherapy (n = 115) or chemotherapy alone (n = 172). Mutation status of 17 HRR genes (BARD1, BLM, BRCA1, BRCA2, BRIP1, MRE11A, NBN, PALB2, PARP1, POLD1, RAD50, RAD51, RAD51C, RAD51D, RAD52, RAD54L, and XRCC2) was assessed using targeted next-generation sequencing.</p><p><strong>Results: </strong>Among patients treated with nivolumab plus chemotherapy, 36.5% had HRR mutations, with BRCA2 mutation being the most common mutation (11.3%). Compared to those of the no-HRR mutation group, the HRR mutation group exhibited a higher objective response rate, longer progression-free survival (PFS) (median 12.8 vs. 6.5 months; hazard ratio HR 0.57), and overall survival (OS) (median not reached vs. 14.2 months; HR 0.40) with nivolumab plus chemotherapy. Patients with HRR mutations treated with nivolumab plus chemotherapy showed favorable PFS and OS compared to those treated with chemotherapy alone. However, this difference was not observed in patients without HRR mutations.</p><p><strong>Conclusions: </strong>HRR mutations were associated with favorable survival outcomes in patients treated with nivolumab plus chemotherapy. Our findings suggest that HRR mutations may serve as a potential predictive biomarker for first-line ICI-based chemotherapy in gastric cancer.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729680","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":"Comparison of clinicopathological features of gastric carcinoma in autoimmune gastritis with and without Helicobacter pylori infection.","authors":"Ayaka Takasu, Toshiaki Hirasawa, Yuka Higashi, Kaoru Nakano, Souya Nunobe, Takuji Gotoda, Hiroshi Kawachi","doi":"10.1007/s10120-025-01649-z","DOIUrl":"https://doi.org/10.1007/s10120-025-01649-z","url":null,"abstract":"<p><strong>Background: </strong>Chronic atrophic gastritis, represented by Helicobacter pylori (H. pylori) or autoimmune gastritis (AIG), has been recognized as a risk factor for gastric carcinoma (GC). Differences in the clinicopathological features of GC with AIG (GC-AIG) based on H. pylori infection status remain unclear.</p><p><strong>Methods: </strong>This retrospective analysis included 65 cases of GC-AIG in which endoscopic resection or gastrectomy was performed at a single center between 2008 and 2024. The cases were categorized into Group A (H. pylori-naïve GC-AIG) or Group B (H. pylori-infected GC-AIG), and the clinical and pathological data were compared between the groups.</p><p><strong>Results: </strong>Group A included 18 cases with 25 lesions and Group B included 47 cases with 72 lesions. The median age [interquartile range] was significantly younger in Group A (70 [63-74] years) than in Group B (75 [62-79] years, p = 0.045). Tumors in Group A were more frequently located in the upper and middle stomach, whereas those in Group B were predominantly located in the lower stomach (p = 0.006). Group A had a significantly higher proportion of pure undifferentiated-type adenocarcinoma (Laurén's diffuse type) than Group B (28.0% versus 8.3%, p = 0.027).</p><p><strong>Conclusions: </strong>H. pylori-naïve GC-AIG is characterized by younger age, a higher prevalence of pure undifferentiated-type adenocarcinoma, and tumors predominantly located in the upper and middle stomach.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707325","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":"Evaluating peritoneal elastic laminal invasion to improve stratification of patients with pT3 gastric cancer.","authors":"Daiki Terajima, Motohiro Kojima, Shingo Sakashita, Tetsuro Taki, Takahiro Kinoshita, Genichiro Ishii, Naoya Sakamoto","doi":"10.1007/s10120-025-01627-5","DOIUrl":"https://doi.org/10.1007/s10120-025-01627-5","url":null,"abstract":"<p><strong>Background: </strong>Elastic laminal invasion (ELI), defined as tumor invasion beyond the peritoneal elastic lamina, may affect gastric cancer (GC) prognosis, though limited data exist on this relationship.</p><p><strong>Methods: </strong>We retrospectively reviewed representative pathological slides from 396 patients with pT3 or pT4a GC who underwent curative resection to assess the association between ELI and relapse-free survival (RFS) and overall survival (OS).</p><p><strong>Results: </strong>The 5-year RFS of pT3 GC with negative ELI was 85.9%, which was better than the 55.9% of that of ELI-positive pT3 (P < 0.001) or pT4a (51.3%) GC (P < 0.001). Similarly, the 5-year OS of ELI-negative pT3 GC was 90.4%, while the corresponding values for ELI-positive pT3 and pT4a were 67.0% (P < 0.001) and 63.6% (P < 0.001), respectively. Multivariate analysis revealed that the most significant prognostic factors for RFS were pT factors (i.e., pT3 with ELI/pT4), tumor size (≥ 80 mm), and nodal metastasis. We subdivided our cohort of patients with pathological stage II (pT3N0, pT3N1) GC into ELI-negative and ELI-positive subgroups, and found that the ELI-negative ones had better RFS percentages than those who were ELI-positive or stage III (P = 0.002 and P < 0.001, respectively).</p><p><strong>Conclusions: </strong>ELI-positive pT3 GC has a worse prognosis than its ELI-negative counterpart, comparable to that of pT4a. These findings suggest a need to revisit the pT grading system in GC.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698352","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":"Clinical impact of primary and secondary KIT mutations on the efficacy of molecular-targeted therapies in gastrointestinal stromal tumors.","authors":"Kota Kawabata, Tsuyoshi Takahashi, Toshirou Nishida, Yukinori Kurokawa, Kazuyoshi Yamamoto, Takuro Saito, Kota Momose, Kotaro Yamashita, Koji Tanaka, Tomoki Makino, Ryohei Kawabata, Atsushi Takeno, Kiyokazu Nakajima, Seiichi Hirota, Hidetoshi Eguchi, Yuichiro Doki","doi":"10.1007/s10120-025-01639-1","DOIUrl":"https://doi.org/10.1007/s10120-025-01639-1","url":null,"abstract":"<p><strong>Background: </strong>Gastrointestinal stromal tumors (GISTs) are commonly driven by primary mutations in KIT or PDGFRA. Imatinib is the first-line therapy for GISTs. However, secondary mutations frequently emerge during imatinib treatment, contributing to resistance and influencing the efficacy of subsequent tyrosine kinase inhibitors, such as sunitinib and regorafenib. This study aimed to investigate the clinical relevance of both primary and secondary KIT mutations in treating and prognosing unresectable or recurrent GISTs.</p><p><strong>Methods: </strong>Ninety patients with unresectable or recurrent GISTs treated at our institution between 2000 and 2017 were retrospectively analyzed. Genetic testing was performed before the initial drug administration to guide first-line imatinib therapy based on the primary mutation profile. In 64 imatinib-resistant patients, additional genetic testing was conducted on tissues obtained from resistant lesions. Treatment response and prognosis were compared across mutational profiles.</p><p><strong>Results: </strong>The most common primary mutation was KIT exon 11 (76.7%), followed by exon 9 (12.2%). Patients with exon 9 mutations showed superior progression-free survival with sunitinib than those with exon 11 mutations. Among patients with exon 11 primary mutations, secondary mutations were identified in 79.2%, predominantly in KIT exon 13/14 (47.9%) or 17/18 (31.3%). Sunitinib was more effective in patients with secondary exon 13/14 mutations, whereas regorafenib was significantly more effective in those with exon 17/18 mutations.</p><p><strong>Conclusions: </strong>Secondary KIT mutations play a crucial role in imatinib resistance and the efficacy of second- and third-line therapies. Genetic profiling at the initial diagnosis and at the time of resistance may provide more personalized and effective treatment strategies.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690015","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":"Assessing efficacy of anti-glypican-1 antibody-drug conjugate as potential therapeutic approach for gastric cancer.","authors":"Yuji Suzuki, Satoshi Serada, Masashi Yamashita, Kota Kawabata, Tsuyoshi Takahashi, Kengo Obata, Akihito Jo, Eiji Funajima, Yuichiro Doki, Tetsuji Naka","doi":"10.1007/s10120-025-01647-1","DOIUrl":"https://doi.org/10.1007/s10120-025-01647-1","url":null,"abstract":"<p><strong>Background: </strong>Despite significant advancements in cancer treatment, gastric cancer (GC) continues to have a high incidence and mortality rate. Antibody-drug conjugates (ADCs) are emerging as a viable treatment option for GC. Glypican-1 (GPC1), a cell surface proteoglycan, has garnered interest for its role in tumor growth and its potential as a biomarker. This study evaluated the efficacy of an ADC comprising a humanized anti-GPC1 monoclonal antibody conjugated with monomethyl auristatin E (GPC1-ADC) to target GPC1 in GC.</p><p><strong>Methods: </strong>GPC1 expression was assessed in GC cell lines and tissues. The cytotoxic efficacy and mechanism of action of GPC1-ADC were evaluated through comprehensive in vitro assays. In vivo efficacy was further assessed in xenograft mouse models, focusing on tumor growth inhibition and its performance against peritoneal dissemination.</p><p><strong>Results: </strong>In vitro, GPC1-ADC exhibited significant cytotoxicity against GPC1-positive cell lines by inducing cell cycle arrest and apoptosis. Additionally, GPC1-ADC demonstrated promising bystander-killing activity via cancer-associated fibroblasts, highlighting its potential to target the heterogeneous tumor microenvironment characteristic of GC. In vivo, GPC1-ADC significantly inhibited tumor growth and demonstrated substantial therapeutic effects in a peritoneal dissemination model. Immunohistochemical analysis of tumor specimens from GC patients revealed that 90.2% of differentiated types and 66.7% of poorly differentiated types exhibited high GPC1 expression. High GPC1 expression in tumor samples was significantly associated with poorer progression-free and overall survival.</p><p><strong>Conclusions: </strong>Our findings suggest that GPC1-targeting ADCs represent a promising therapeutic option for GPC1-positive GC.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690014","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":"Nuclear export of transmembrane protein PROM2 is specially regulated by CRM1 and affects the sensitivity of ferroptosis in gastric cancer.","authors":"Panpan Zhang, Wenbo Lin, Ting Wu, Shihao Rao, Danwei Huang, Jing Wu, Tao Tao, Jingjing Hou","doi":"10.1007/s10120-025-01642-6","DOIUrl":"https://doi.org/10.1007/s10120-025-01642-6","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) exhibits high mortality and poor prognosis, with ferroptosis playing a critical role in its progression. More recent research suggests that PROM2 are closely associated with MVBs (Multivesicular Bodies) which is essential to ferroptosis, and may represent key molecules involved in the resistance of tumor cells to ferroptosis.</p><p><strong>Methods: </strong>The study employed RSL3-induced ferroptosis models to analyze mitochondrial damage, ROS accumulation, and iron dysregulation. PROM2 expression was assessed under varying RSL3 concentrations and durations. Co-immunoprecipitation and structural modeling elucidated the CRM1-PROM2 interaction. Clinical correlations were evaluated using GC tissue samples. In vivo animal experiments tested the effects of PROM2 and CRM1 inhibition on tumor growth.</p><p><strong>Results: </strong>RSL3 inhibits cell proliferation and induces ferroptosis in GC cells, concomitant with increased PROM2 expression. PROM2 Knockdown potentiates ferroptosis sensitivity and augments RSL3-induced cell death. Clinically, elevated PROM2 correlates with poor prognosis in GC patients. In vivo, PROM2 inhibition suppresses xenograft tumor growth and enhances ferroptosis susceptibility. Mechanistically, PROM2 interacts with CRM1 whose inhibition by LMB (Leptomycin B) impairs cell proliferation and promotes ferroptosis. Nucleocytoplasmic translocation of PROM2 is CRM1-dependent, and CRM1 expression positively correlates with PROM2 in GC tissues. CRM1 depletion synergizes with RSL3 to suppress tumor growth in xenograft models.</p><p><strong>Conclusions: </strong>These findings delineate a CRM1-PROM2 signaling axis that governs ferroptosis sensitivity in GC, wherein CRM1-mediated nuclear export of PROM2 during ferroptosis represents a critical regulatory node. Targeting this axis may offer novel diagnostic and therapeutic strategies for GC and other malignancies.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659076","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":"Concurrent hypermethylation of CpG islands and hypomethylation of CpG-poor regions are associated with gastric cancer risk after Helicobacter pylori eradication.","authors":"Gota Sudo, Eiichiro Yamamoto, Takeshi Niinuma, Mitsunobu Saito, Hiroshi Kitajima, Kazuya Ishiguro, Akira Yorozu, Mutsumi Toyota, Hironori Aoki, Kei Mitsuhashi, Shinji Yoshii, Hiro-O Yamano, Masashi Idogawa, Reo Maruyama, Tamotsu Sugai, Hiroshi Nakase, Hiromu Suzuki","doi":"10.1007/s10120-025-01646-2","DOIUrl":"https://doi.org/10.1007/s10120-025-01646-2","url":null,"abstract":"<p><strong>Background and aim: </strong>Aberrant DNA methylation persists in the gastric mucosa after Helicobacter pylori (H. pylori) eradication and may contribute to the development of post-eradication gastric cancer (PEGC). We aimed to comprehensively investigate both DNA hypermethylation and hypomethylation and their relevance to cancer risk.</p><p><strong>Methods: </strong>Genome-wide DNA methylation profiling was performed using Infinium MethylationEPIC BeadChips with tumor tissue and non-cancerous mucosa from PEGC patients. Public datasets, including The Cancer Genome Atlas (TCGA)-STAD and H. pylori-negative controls, were integrated to identify recurrently hyper- and hypomethylated loci. Representative gene methylation levels were validated using bisulfite pyrosequencing. Correlation analyses were conducted to link DNA methylation with gene expression.</p><p><strong>Results: </strong>Non-cancerous mucosa from PEGC patients exhibited substantial CpG island (CGI) hypermethylation. In parallel, we detected 4081 CpG sites recurrently hypomethylated in GC, many of which were also hypomethylated in non-cancerous mucosa from PEGC patients. The majority of hypomethylated sites were located outside of CGIs, often near oncogenes such as CDH17, HNF4A and CD44, and showed inverse correlations with gene expression. CGI hypermethylation and CpG hypomethylation were positively correlated across samples.</p><p><strong>Conclusions: </strong>CGI hypermethylation and non-CGI hypomethylation are tightly linked and may co-emerge during the early stages of gastric carcinogenesis. Their concurrent presence in non-cancerous mucosa from PEGC patients suggests a coordinated epigenetic landscape contributing to residual cancer risk after H. pylori eradication.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642456","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}