Gastric Cancer最新文献

{"title":"Nationwide survey on HER2 and PD-L1 testing practices in gastric cancer across Japan.","authors":"Hiroyuki Abe, Takeshi Kuwata, Ryoji Kushima, Tetsuo Ushiku","doi":"10.1007/s10120-024-01571-w","DOIUrl":"10.1007/s10120-024-01571-w","url":null,"abstract":"<p><strong>Background: </strong>Since HER2 and PD-L1 testing are key to selecting drugs for first-line treatments in advanced gastric cancer, evaluating differences in these tests among institutions is necessary to standardize treatment.</p><p><strong>Methods: </strong>A questionnaire survey was conducted targeting institutions certified by the Japanese Gastric Cancer Association.</p><p><strong>Results: </strong>Responses were obtained from 155 institutions. Most institutions performed HER2 testing in-house, while PD-L1 tests were largely outsourced. HER2 scores and PD-L1 CPS rates showed greater variability across institutions than anticipated. In the pre-analytic phase, 10% neutral buffered formalin was commonly used, with fixation practices generally following guidelines. Overall, the impact of fixation-related factors was limited, but in surgical specimens, longer fixation was associated with a higher proportion of score 0/1+ and a lower proportion of score 3+. When examining HER2 scores by institution, if a particular score had a high (or low) frequency in biopsy, the same trend was also seen in surgical specimens.</p><p><strong>Conclusions: </strong>These findings suggest that not only factors related to specimen preparation, but also biases in evaluation criteria among pathologists may contribute to the significant variability among institutions. Standardization of pre- and post-analytic phases, coupled with appropriate training, is essential to achieve consistent gastric cancer therapy.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"294-300"},"PeriodicalIF":6.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800383","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":"Expression of therapy target molecules in esophagogastric junction and Barrett's adenocarcinoma.","authors":"Hiroyuki Abe, Masayuki Urabe, Koichi Yagi, Hiroharu Yamashita, Yasuyuki Seto, Tetsuo Ushiku","doi":"10.1007/s10120-024-01573-8","DOIUrl":"10.1007/s10120-024-01573-8","url":null,"abstract":"<p><strong>Background: </strong>Recently, novel molecular targeted therapies have been developed for gastric and esophageal adenocarcinomas. We examined the status of therapeutic target molecules in esophagogastric junction (EGJ) and Barrett's adenocarcinoma.</p><p><strong>Methods: </strong>Tissue microarrays were constructed from 114 cases of non-Barrett's EGJ adenocarcinoma and 30 cases of Barrett's adenocarcinoma. Immunohistochemistry for mismatch repair proteins, PD-L1, HER2, CLDN18, FGFR2b, and EBER-ISH was performed. When HER2 immunohistochemistry was 2 + , gene amplification was examined using in situ hybridization.</p><p><strong>Results: </strong>EBER positivity, mismatch repair deficiency, PD-L1 combined positive score (CPS) ≥ 1, CLDN18 expression ≥ 75%, FGFR2b expression, and HER2 positivity were observed in 7 (6.1%), 11 (9.6%), 70 (61.4%), 38 (33.3%), 6 (5.3%), and 11 (9.6%) cases of EGJ adenocarcinoma as well as in 0 (0%), 0 (0%), 23 (76.7%), 7 (23.3%), 2 (6.7%), and 6 (20.0%) cases of Barrett's adenocarcinoma, respectively. PD-L1 CPS ≥ 1 cases had longer recurrence-free survival (P = 0.001) and overall survival (P = 0.003) than CPS < 1 cases. Other target molecules were not associated with survival. A total of 93/114 (81.6%) cases of EGJ adenocarcinoma and 26/30 (86.7%) cases of Barrett's adenocarcinomas expressed at least one target molecule.</p><p><strong>Conclusions: </strong>Most EGJ and Barrett's adenocarcinomas may be eligible for molecular targeted therapy. Appropriate patient stratification based on these molecular tests will be important for precision medicine of the EGJ and Barrett's adenocarcinoma.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"264-274"},"PeriodicalIF":6.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812758","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":"SUSD2⁺ cancer-associated fibroblasts in gastric cancer mediate the effect of immunosuppression and predict overall survival and the effectiveness of neoadjuvant immunotherapy.","authors":"Rishun Su, Xuezeng Sun, Yusheng Luo, Liang Gu, Fulin Wang, Aoran Dong, Masami Yamamoto, Tetsuya Tsukamoto, Sachiyo Nomura, Zhenzhen Zhao, Chen Dai, Guofei Deng, Baoding Zhuang, Yulong He, Changhua Zhang, Songcheng Yin","doi":"10.1007/s10120-024-01572-9","DOIUrl":"10.1007/s10120-024-01572-9","url":null,"abstract":"<p><strong>Background: </strong>The expression patterns and functions of Sushi Domain Containing 2 (SUSD2) differ among various malignancies. This research aims to investigate the expression of SUSD2 and the role of the SUSD2⁺ cancer-associated fibroblasts (CAFs) for immunotherapy in gastric cancer.</p><p><strong>Methods: </strong>The expression of SUSD2 and specific markers (CD4, CD8, PD-1, TIGIT, TIM-3 and CD163) was determined using immunohistochemistry and multiplex immunofluorescence (mIHC) on paraffin sections. Flow cytometry and western blot were used to assess the expression of SUSD2 in fibroblasts from fresh samples. Also, analysis of single-cell and bulk RNA sequencing was employed to confirm the presence and characterize the function of SUSD2⁺ CAFs. The predictive power of indicators for neoadjuvant immunotherapy was evaluated via ROC curve analysis. Animal experiment was employed to validate the immunosuppressive effect of SUSD2⁺ CAFs.</p><p><strong>Results: </strong>SUSD2 is mainly expressed on fibroblasts within the tumors and the high infiltration of SUSD2⁺ CAFs went together with a poor survival and a more advanced tumor stage. Significantly, the joint use of SUSD2⁺ CAFs and CD8⁺ T cells demonstrated a remarkable ability to predict the efficacy of neoadjuvant immunotherapy superior to PD-L1 combined positive score. High SUSD2⁺ CAFs was correlated with resistance to immunotherapy as well as low CD8⁺ T infiltration and high exhausted T cell infiltration.</p><p><strong>Conclusions: </strong>We have identified a novel subset of CAFs that could predict the survival and response to neoadjuvant immunotherapy of patients. The SUSD2⁺ CAFs have the potential to serve as a predictive biomarker and a promising target for immunotherapy.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"245-263"},"PeriodicalIF":6.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800386","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":"Short-term outcomes of preoperative computed tomography angiography versus standard assessment in patients with BMI ≥ 25.0 kg/m² undergoing laparoscopic gastrectomy: the GISSG20-01 randomized clinical trial.","authors":"Cheng Meng, Shougen Cao, Leping Li, Lijian Xia, Xianqun Chu, Lixin Jiang, XinJian Wang, Hao Wang, Shusheng Huang, Quanhong Duan, Zuocheng Sun, Qingsi He, Xizeng Hui, Daogui Yang, Huanhu Zhang, Zequn Li, Xiaodong Liu, Yulong Tian, Yuqi Sun, Yu Li, Haitao Jiang, Zhaojian Niu, Jian Zhang, Yanbing Zhou","doi":"10.1007/s10120-024-01580-9","DOIUrl":"10.1007/s10120-024-01580-9","url":null,"abstract":"<p><strong>Background: </strong>Laparoscopic gastrectomy lacks hand-direct tactile sense and has a limited surgical field compared to laparotomy. Apart from textbook classification, there are anatomical variations in the gastric arteries. Laparoscopic gastrectomy presents technical difficulties and necessitates a more comprehensive comprehension of regional anatomy than open surgical procedures. We aimed to compare efficacy and safety of preoperative computed tomography angiography (CTA) associated with surgical decision-making for laparoscopic gastrectomy.</p><p><strong>Methods: </strong>The GISSG 20-01 study was a multicenter, open-label, randomized clinical trial. The enrollment criteria mainly included histologically confirmed gastric cancer patients with BMI ≥ 25 kg/m². Eligible patients were randomly assigned to the CTA group or the non-CTA group in a 1:1 ratio. The primary endpoint was the volume of intraoperative blood loss.</p><p><strong>Results: </strong>Between November 2020 and December 2021, 382 patients were enrolled and randomly assigned. After exclusion of 25 patients, 357 patients were included in the modified intention-to-treat population (179 in the CTA group and 178 in the non-CTA group). The mean intraoperative blood loss (CTA vs non-CTA; 74.2 vs 95.0 mL, P = 0.005) and operation time (215.4 vs 231.2 min, P = 0.004) was significantly lower in the CTA group. Total number of retrieved lymph nodes was similar in two groups (32.2 vs 30.2, P = 0.070). The CTA group had a significantly lower surgery task load index sore than the non-CTA group (36.6 vs 41.7, P < 0.001). There was no significant difference in postoperative complications rate of 14.5% in the CTA group and 22.5% in the non-CTA group (difference, - 8.0% [95% CI, - 16.0 to 0.1]; P = 0.053).</p><p><strong>Conclusion: </strong>Preoperative CTA associated with surgical decision-making could relieve surgery burden and lead to a better surgical performance compared with non-CTA support, which including decreased blood loss volume, vessel damage and operation time.</p><p><strong>Trial registration: </strong>NCT04636099.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"283-293"},"PeriodicalIF":6.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947522","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":"Hazard rates of recurrence for gastric cancer after curative resection: implications for postoperative surveillance.","authors":"Kyohei Kanematsu, Yuta Nakayama, Mie Tanabe, Junya Morita, Shinsuke Nagasawa, Takanobu Yamada, Takashi Ogata, Takashi Oshima","doi":"10.1007/s10120-024-01576-5","DOIUrl":"10.1007/s10120-024-01576-5","url":null,"abstract":"<p><strong>Background: </strong>Identifying the most effective postoperative surveillance interval in patients with gastric cancer (GC) remains challenging. To elucidate a logical and effective surveillance schedule, we analyzed GC recurrence risk trends after gastrectomy using the hazard function.</p><p><strong>Methods: </strong>We retrospectively reviewed the medical records of 2503 patients who underwent curative GC resection between 2000 and 2018. We examined recurrence risk over time and the influence of clinicopathological variables on it.</p><p><strong>Results: </strong>Overall, GC recurred in 291 patients (11.6%) over a median of 64.6 months. Recurrence risk was highest at approximately 11-months postoperatively (hazard rate [HR]: 0.0045), decreasing to half the peak at approximately 39-months postoperatively. Patients with Stage I GC maintained a low risk. In Stage II patients, the risk peaked at 16-months postoperatively (HR: 0.006) and gradually declined thereafter. Stage III patients had the highest risk at 11 months postoperatively (HR: 0.019), plateauing at 40 months.</p><p><strong>Conclusions: </strong>We demonstrated significant cancer stage-dependent differences in postsurgical GC recurrence risk by using the hazard function. Reductions in surveillance intensity might be acceptable according to the individual risk of recurrence.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"275-282"},"PeriodicalIF":6.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894152","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":"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}