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Comment on "Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for new-onset gastric cancer and gastric diseases in patients with type 2 diabetes mellitus: a population-based cohort study". 就 "钠-葡萄糖共转运体-2 抑制剂对 2 型糖尿病患者新发胃癌和胃病的疗效比较:一项基于人群的队列研究 "发表评论。
IF 6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-04 DOI: 10.1007/s10120-024-01531-4
Kuan-Fu Liao, Shih-Wei Lai
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引用次数: 0
Acknowledgment to Reviewers. 感谢审稿人。
IF 6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-23 DOI: 10.1007/s10120-024-01559-6
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引用次数: 0
Real-world effectiveness and safety of trastuzumab-deruxtecan in Japanese patients with HER2-positive advanced gastric cancer (EN-DEAVOR study). 在日本 HER2 阳性晚期胃癌患者中使用曲妥珠单抗-得舒坦的实际有效性和安全性(EN-DEAVOR 研究)。
IF 6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-10 DOI: 10.1007/s10120-024-01555-w
Hisato Kawakami, Koki Nakanishi, Akitaka Makiyama, Hirotaka Konishi, Satoshi Morita, Yukiya Narita, Naotoshi Sugimoto, Keiko Minashi, Motohiro Imano, Rin Inamoto, Yasuhiro Kodera, Hiroki Kume, Keita Yamaguchi, Wataru Hashimoto, Kei Muro

Background: Trastuzumab-deruxtecan (T-DXd) was approved for the treatment of HER2-positive patients with advanced gastric cancer in Japan based on the results of the DESTINY-Gastric01 trial. This study aimed to collect real-world data and evaluate the effectiveness and safety of T-DXd.

Methods: Patients aged ≥ 20 years at the start of T-DXd administration with a histopathologically confirmed diagnosis of HER2-positive unresectable advanced or recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma that had worsened after chemotherapy were enrolled in this retrospective cohort study. Key outcomes included T-DXd treatment status, overall survival (OS), real-world progression-free survival (rwPFS), time to treatment failure (TTF), objective response rate and frequency of grade ≥ 3 adverse events (AEs).

Results: Of the 312 patients included in the analysis, 75.3% were male, the median (range) age was 70.0 (27.0-89.0) years, 12.2% had an ECOG PS ≥ 2, 43.3% had ascites and the initial T-DXd dose was > 5.4- ≤ 6.4 mg/kg in 78.2% of patients. The median (95% confidence interval) OS, rwPFS and TTF (months) was 8.9 (8.0-11.0), 4.6 (4.0-5.1) and 3.9 (3.4-4.2), respectively. The response rate was 42.9% in patients with a target lesion. In total, 48.4% of patients experienced a grade ≥ 3 AE, 2.6% experienced grade 5 AEs and 60.9% experienced AEs leading to T-DXd dose adjustments (reduction: 36.9%, interruption: 34.0% or discontinuation: 23.7%). No new safety signals were detected.

Conclusions: T-DXd was effective and had a manageable safety profile as a third- or later-line treatment for patients with HER2-positive gastric or GEJ cancer in Japanese clinical practice.

Clinical trial registration: UMIN000049032.

背景:根据DESTINY-Gastric01试验的结果,日本批准曲妥珠单抗-德鲁司康(Trastuzumab-deruxtecan,T-DXd)用于治疗HER2阳性的晚期胃癌患者。本研究旨在收集真实世界的数据,评估T-DXd的有效性和安全性:这项回顾性队列研究招募了开始服用 T-DXd 时年龄≥ 20 岁、组织病理学确诊为 HER2 阳性不可切除的晚期或复发性胃癌或胃食管交界处(GEJ)腺癌且化疗后病情恶化的患者。主要结果包括T-DXd治疗状态、总生存期(OS)、实际无进展生存期(rwPFS)、治疗失败时间(TTF)、客观反应率和≥3级不良事件(AEs)频率:在纳入分析的312例患者中,75.3%为男性,中位(范围)年龄为70.0(27.0-89.0)岁,12.2%的患者ECOG PS≥2,43.3%的患者有腹水,78.2%的患者初始T-DXd剂量> 5.4-≤ 6.4 mg/kg。OS、rwPFS和TTF的中位数(95%置信区间)分别为8.9(8.0-11.0)、4.6(4.0-5.1)和3.9(3.4-4.2)个月。靶病灶患者的应答率为42.9%。共有48.4%的患者出现了≥3级AE,2.6%出现了5级AE,60.9%出现了导致T-DXd剂量调整的AE(减量:36.9%,中断:34.0%或停药:23.7%)。未发现新的安全信号:结论:在日本临床实践中,T-DXd作为HER2阳性胃癌或胃食管癌患者的三线或后线治疗药物,疗效显著,安全性可控:临床试验注册:UMIN000049032。
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引用次数: 0
Neoadjuvant chemotherapy in relation to long-term mortality in individuals cured of gastric adenocarcinoma. 新辅助化疗与胃腺癌治愈者长期死亡率的关系。
IF 6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-10 DOI: 10.1007/s10120-024-01558-7
Wilhelm Leijonmarck, Fredrik Mattsson, Jesper Lagergren

Background: Late effects of chemotherapy could affect mortality amongst cancer survivors. This study aimed to clarify if neoadjuvant chemotherapy for gastric adenocarcinoma influences the long-term survival in individuals cured of this tumour.

Methods: This was a nationwide and population-based cohort study that included all individuals who underwent gastrectomy for gastric adenocarcinoma in Sweden between 2006 and 2015 and survived for ≥ 5 years after surgery. The cohort was followed up until death or end of study period (31 December 2020). Multivariable Cox proportional hazards regression was used to provide hazard ratios (HR) with 95% confidence intervals (CI). The HR were adjusted for age, sex, comorbidity, education, calendar year, tumour sub-location, in-hospital complications, and splenectomy. Data came from medical records and nationwide registers.

Results: Amongst 613 gastric adenocarcinoma survivors, neoadjuvant chemotherapy (used in 269 patients; 43.9%) was associated with a decreased crude mortality rate (HR 0.66, 95% CI 0.46-0.96). However, the association attenuated and became statistically non-significant after adjustment for all confounders (HR 0.83, 95% CI 0.56-1.23) and after adjustments solely for age and comorbidity (HR 0.82, 95% CI 0.56-1.20). Stratified analyses did not reveal any statistically significant associations between neoadjuvant chemotherapy and long-term mortality in categories of age, sex, comorbidity, calendar year and tumour sub-location.

Conclusion: Neoadjuvant chemotherapy did not decrease the long-term survival amongst gastric adenocarcinoma survivors. Patients who received neoadjuvant chemotherapy were a selected group characterised by younger age and fewer severe comorbidities and therefore with better chances of long-term survival.

背景:化疗的晚期效应可能会影响癌症幸存者的死亡率。本研究旨在明确胃腺癌新辅助化疗是否会影响该肿瘤治愈者的长期生存:这是一项基于人口的全国性队列研究,研究对象包括2006年至2015年间在瑞典因胃腺癌接受胃切除术且术后存活≥5年的所有患者。队列随访至死亡或研究期结束(2020 年 12 月 31 日)。采用多变量考克斯比例危险度回归法得出危险度比 (HR),并得出 95% 的置信区间 (CI)。HR已根据年龄、性别、合并症、教育程度、日历年、肿瘤亚位置、院内并发症和脾切除术进行了调整。数据来自医疗记录和全国范围内的登记:结果:在 613 名胃癌幸存者中,新辅助化疗(269 名患者,43.9%)与粗死亡率的降低有关(HR 0.66,95% CI 0.46-0.96)。然而,在对所有混杂因素进行调整后(HR 0.83,95% CI 0.56-1.23),以及仅对年龄和合并症进行调整后(HR 0.82,95% CI 0.56-1.20),这种关联性减弱,在统计学上变得不显著。分层分析未发现新辅助化疗与年龄、性别、合并症、日历年和肿瘤亚定位等类别的长期死亡率有任何统计学意义:结论:新辅助化疗不会降低胃腺癌幸存者的长期生存率。接受新辅助化疗的患者是经过筛选的群体,他们的特点是年龄较小、严重合并症较少,因此长期生存的机会更大。
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引用次数: 0
Circulating tumor DNA predicts recurrence and survival in patients with resectable gastric and gastroesophageal junction cancer. 循环肿瘤DNA可预测可切除胃癌和胃食管交界处癌患者的复发率和生存率。
IF 6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-05 DOI: 10.1007/s10120-024-01556-9
Cecilie Riis Iden, Salah Mohammad Mustafa, Nadia Øgaard, Tenna Henriksen, Sarah Østrup Jensen, Lise Barlebo Ahlborn, Kristian Egebjerg, Lene Baeksgaard, Rajendra Singh Garbyal, Mette Kjølhede Nedergaard, Michael Patrick Achiam, Claus Lindbjerg Andersen, Morten Mau-Sørensen

Background: Gastric and gastroesophageal junction (GEJ) cancer represents a significant global health challenge, with high recurrence rates and poor survival outcomes. This study investigates circulating tumor DNA (ctDNA) as a biomarker for assessing recurrence risk in patients with resectable gastric and GEJ adenocarcinomas (AC).

Methods: Patients with resectable gastric and GEJ AC, undergoing perioperative chemotherapy and surgery, were prospectively enrolled. Serial plasma samples were collected at baseline, after one cycle of chemotherapy, after preoperative chemotherapy, and after surgery. ctDNA was assessed by a ddPCR test (TriMeth), which targets the gastrointestinal cancer-specific methylation patterns of the genes C9orf50, KCNQ5, and CLIP4.

Results: ctDNA analysis was performed on 229 plasma samples from 86 patients. At baseline, ctDNA was detected in 56% of patients, which decreased to 37% following one cycle of chemotherapy, 25% after preoperative chemotherapy and 15% after surgical resection. The presence of ctDNA after one cycle of chemotherapy was associated with reduced recurrence-free survival (RFS) (HR = 2.54, 95% confidence interval (CI) 1.33-4.85, p = 0.005) and overall survival (OS) (HR = 2.23, 95% CI 1.07-4.62, p = 0.032). Similarly, ctDNA after surgery was associated with significantly shorter RFS (HR = 6.22, 95% CI 2.39-16.2, p < 0.001) and OS (HR = 6.37, 95% CI 2.10-19.3, p = 0.001). Multivariable regression analysis confirmed ctDNA after surgery as an independent prognostic factor (p < 0.001).

Conclusion: ctDNA analysis has the potential to identify patients at elevated risk of recurrence, thus providing personalized treatment strategies for patients with resectable gastric and GEJ cancer. Further validation in larger cohorts and ctDNA-guided interventions are needed for future clinical use.

背景:胃癌和胃食管交界处癌(GEJ)复发率高、生存率低,是全球健康面临的重大挑战。本研究将循环肿瘤 DNA(ctDNA)作为一种生物标记物,用于评估可切除胃癌和胃食管连接部腺癌(AC)患者的复发风险:方法:对接受围手术期化疗和手术的可切除胃癌和胃食管腺癌患者进行前瞻性研究。ctDNA通过ddPCR检测(TriMeth)进行评估,该检测针对C9orf50、KCNQ5和CLIP4基因的胃肠癌特异性甲基化模式。结果:对86名患者的229份血浆样本进行了ctDNA分析。基线时,56%的患者检测到ctDNA,化疗一个周期后降至37%,术前化疗后降至25%,手术切除后降至15%。一个化疗周期后出现ctDNA与无复发生存期(RFS)(HR = 2.54,95% 置信区间(CI)1.33-4.85,p = 0.005)和总生存期(OS)(HR = 2.23,95% 置信区间(CI)1.07-4.62,p = 0.032)降低有关。同样,手术后ctDNA与明显较短的RFS相关(HR = 6.22,95% CI 2.39-16.2,p 结论:ctDNA分析有可能识别复发风险较高的患者,从而为可切除胃癌和GEJ癌患者提供个性化治疗策略。未来的临床应用还需要在更大的队列中进一步验证,并在ctDNA指导下进行干预。
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引用次数: 0
Prognostic significance of tertiary lymphoid structures in gastric neuroendocrine carcinoma with association to delta-like ligand 3 and neuroendocrine expressions. 胃神经内分泌癌三级淋巴结构的预后意义与 delta 样配体 3 和神经内分泌表达相关。
IF 6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-01 DOI: 10.1007/s10120-024-01557-8
Bokyung Ahn, Deokhoon Kim, Mi-Ju Kim, Seo-Rin Jeong, In Hye Song, Joo Young Kim, Soon Auck Hong, Sun-Young Jun, HyungJun Cho, Young Soo Park, Freddy E Escorcia, Joon-Yong Chung, Seung-Mo Hong

Background: Gastric neuroendocrine carcinomas (NECs) are rare cancers with highly aggressive behavior. Although tertiary lymphoid structures (TLSs) are well-known prognostic factors in various cancers, their role in gastric NECs remain unexplored. Unique immunohistochemical subtypes of pulmonary NECs have been discovered, however, their feasibility in gastric NECs is unknown.

Methods: The presence and maturation of TLSs (lymphoid aggregates, primary and secondary follicles) were assessed in 48 surgically resected gastric NECs and were compared with immunohistochemical subtypes, using a panel of ASCL1, NeuroD1, POU2F3, YAP1, and DLL3 with three neuroendocrine (NE) markers.

Results: Patients with secondary follicles had significantly better overall survival (OS) and recurrence-free survival (RFS; both, p = 0.004) than those without them. Based on the hierarchical clustering, gastric NECs were classified into all low/negative (31%), high-YAP1 (19%), high-DLL3/low-NE (29%), and high-NE (21%) expression groups. The high-DLL3/low-NE group was associated with absent TLSs (p = 0.026) and showed the worst OS (p = 0.026). Distant metastasis and a lack of secondary follicles were poor independent prognostic factors of OS and RFS.

Conclusion: The assessment of TLSs is a feasible and potent biomarker for gastric NECs, thus enabling better prognosis and more effective immunotherapy. Furthermore, gastric NECs can be categorized as four immunohistochemically distinct groups, of which the high-DLL3/low-NE group has the worst OS with lack of TLSs.

背景:胃神经内分泌癌(NEC胃神经内分泌癌(NEC)是一种罕见的癌症,具有高度侵袭性。虽然三级淋巴结构(TLSs)是众所周知的各种癌症的预后因素,但它们在胃神经内分泌癌中的作用仍有待探索。肺NECs的独特免疫组化亚型已被发现,但它们在胃NECs中的可行性尚不清楚:方法:在 48 例手术切除的胃 NECs 中评估了 TLS(淋巴聚集、初级和次级滤泡)的存在和成熟情况,并与免疫组化亚型进行了比较,使用了 ASCL1、NeuroD1、POU2F3、YAP1 和 DLL3 以及三种神经内分泌(NE)标记物:结果:有继发性卵泡的患者的总生存期(OS)和无复发生存期(RFS;均为P = 0.004)明显优于无继发性卵泡的患者。根据分层聚类,胃NEC被分为所有低/阴性(31%)、高YAP1(19%)、高DLL3/低NE(29%)和高NE(21%)表达组。高DLL3/低NE组与TLS缺失有关(p = 0.026),其OS最差(p = 0.026)。远处转移和缺乏次级卵泡是OS和RFS的不良独立预后因素:结论:TLSs评估是胃NECs可行且有效的生物标志物,因此能更好地预后和更有效地进行免疫治疗。此外,胃 NECs 可分为四个免疫组化不同的组别,其中高 DLL3/ 低 NE 组的 OS 最差,且缺乏 TLSs。
{"title":"Prognostic significance of tertiary lymphoid structures in gastric neuroendocrine carcinoma with association to delta-like ligand 3 and neuroendocrine expressions.","authors":"Bokyung Ahn, Deokhoon Kim, Mi-Ju Kim, Seo-Rin Jeong, In Hye Song, Joo Young Kim, Soon Auck Hong, Sun-Young Jun, HyungJun Cho, Young Soo Park, Freddy E Escorcia, Joon-Yong Chung, Seung-Mo Hong","doi":"10.1007/s10120-024-01557-8","DOIUrl":"https://doi.org/10.1007/s10120-024-01557-8","url":null,"abstract":"<p><strong>Background: </strong>Gastric neuroendocrine carcinomas (NECs) are rare cancers with highly aggressive behavior. Although tertiary lymphoid structures (TLSs) are well-known prognostic factors in various cancers, their role in gastric NECs remain unexplored. Unique immunohistochemical subtypes of pulmonary NECs have been discovered, however, their feasibility in gastric NECs is unknown.</p><p><strong>Methods: </strong>The presence and maturation of TLSs (lymphoid aggregates, primary and secondary follicles) were assessed in 48 surgically resected gastric NECs and were compared with immunohistochemical subtypes, using a panel of ASCL1, NeuroD1, POU2F3, YAP1, and DLL3 with three neuroendocrine (NE) markers.</p><p><strong>Results: </strong>Patients with secondary follicles had significantly better overall survival (OS) and recurrence-free survival (RFS; both, p = 0.004) than those without them. Based on the hierarchical clustering, gastric NECs were classified into all low/negative (31%), high-YAP1 (19%), high-DLL3/low-NE (29%), and high-NE (21%) expression groups. The high-DLL3/low-NE group was associated with absent TLSs (p = 0.026) and showed the worst OS (p = 0.026). Distant metastasis and a lack of secondary follicles were poor independent prognostic factors of OS and RFS.</p><p><strong>Conclusion: </strong>The assessment of TLSs is a feasible and potent biomarker for gastric NECs, thus enabling better prognosis and more effective immunotherapy. Furthermore, gastric NECs can be categorized as four immunohistochemically distinct groups, of which the high-DLL3/low-NE group has the worst OS with lack of TLSs.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345040","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}
引用次数: 0
Clinical epidemiology of the endoscopic, laparoscopic, and surgical resection of malignant gastric tumors in Japan, 2014-2021: a retrospective study using open data from a national claims database. 2014-2021年日本恶性胃肿瘤内镜、腹腔镜和手术切除的临床流行病学:一项利用全国索赔数据库公开数据进行的回顾性研究。
IF 6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-09-28 DOI: 10.1007/s10120-024-01553-y
Akahito Sako, Tomoyuki Yada, Keiichi Fujiya, Ryo Nakashima, Kensuke Yoshimura, Hidekatsu Yanai, Naomi Uemura

Background: Gastric cancer is a common malignancy with a high incidence in East Asia. Gastric resection ranges from endoscopic resection to open total gastrectomy. However, nationwide data are lacking.

Methods: This observational study analyzed data from the publicly accessible National Database of Health Insurance Claims and Specific Health Checkups, which includes most national health insurance claims data in Japan. Trends in the types of resection performed for malignant gastric tumors between 2014 and 2021, patients' age and sex distributions, and regional disparities were investigated.

Results: The annual number of resections was highest in 2015 (109,000) and lowest in 2020 (90,000) after the COVID-19 pandemic. The proportion of endoscopic resections increased from 47% in 2014 to 57% in 2021 while that of total gastrectomies decreased from 17 to 10%. In 2021, 70% of patients who underwent resection were men. That year, 83.8% of all patients who underwent any type of gastric resection and 87.1% of those who underwent endoscopic submucosal dissection were aged ≥ 65 years. The annual incidence of gastric resection per million population was highest in Tottori (n = 1236) and lowest in Okinawa (n = 251). The proportion of endoscopic resections was highest in Miyagi (66%) and lowest in Aichi (45%) and that of open surgery was highest in Aomori (36%) and lowest in Wakayama (5%).

Conclusions: Gastric malignancy is increasingly treated by endoscopic submucosal dissection rather than open total gastrectomy. However, regional disparities remain in resection type. Standardization of treatment and a more even distribution of specialists are needed.

背景:胃癌是一种常见的恶性肿瘤,在东亚发病率很高。胃切除术包括内镜下切除术和开腹全胃切除术。然而,目前尚缺乏全国性的数据:这项观察性研究分析了可公开访问的 "全国健康保险索赔和特定健康检查数据库 "中的数据,该数据库包括日本大多数全国健康保险索赔数据。研究调查了 2014 年至 2021 年间胃恶性肿瘤切除术的类型趋势、患者的年龄和性别分布以及地区差异:结果:在 COVID-19 大流行之后,每年的切除数量在 2015 年最高(109,000 例),在 2020 年最低(90,000 例)。内镜下切除术的比例从2014年的47%增至2021年的57%,而全胃切除术的比例则从17%降至10%。2021年,70%的切除患者为男性。当年,83.8%接受任何类型胃切除术的患者和87.1%接受内镜黏膜下剥离术的患者年龄≥65岁。每百万人口中,鸟取县的胃切除术年发生率最高(n = 1236),冲绳县最低(n = 251)。宫城县内镜切除比例最高(66%),爱知县最低(45%);青森县开放手术比例最高(36%),和歌山县最低(5%):胃恶性肿瘤越来越多地采用内镜下粘膜下剥离术治疗,而不是开腹全胃切除术。结论:越来越多的胃恶性肿瘤采用内镜下粘膜下剥离术治疗,而不是开腹全胃切除术。需要实现治疗的标准化和专家分布的更均衡。
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引用次数: 0
Lipolysis-stimulated lipoprotein receptor promote lipid uptake and fatty acid oxidation in gastric cancer 溶脂刺激脂蛋白受体促进胃癌的脂质吸收和脂肪酸氧化
IF 7.4 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-09-19 DOI: 10.1007/s10120-024-01552-z
Kota Kawabata, Tsuyoshi Takahashi, Koji Tanaka, Yukinori Kurokawa, Kazuyoshi Yamamoto, Takuro Saito, Kota Momose, Kotaro Yamashita, Tomoki Makino, Takashi Yokouchi, Kunihiko Kawai, Satoshi Serada, Minoru Fujimoto, Kiyokazu Nakajima, Tetsuji Naka, Hidetoshi Eguchi, Yuichiro Doki

Background

Lipolysis-stimulated lipoprotein receptor (LSR), a lipid receptor, is associated with cancer progression. However, detailed effects on intracellular metabolism are unclear. We aimed to elucidate the mechanism of LSR-mediated lipid metabolism in gastric cancer.

Methods

We investigated lipid metabolic changes induced by lipoprotein administration in gastric cancer cells and evaluated the significance of LSR expression and lipid droplets formation in gastric cancer patients. The efficacy of inhibiting β-oxidation in gastric cancer cells was also examined in vitro and vivo.

Results

In gastric cancer cells, LSR promoted cellular uptake of lipoprotein and cell proliferation. Furthermore, the inhibition of LSR in gastric cancer cells expressing high levels of LSR counteracted both effects. Immunohistochemical analysis of human gastric cancer tissues showed that the increase in lipid droplets via LSR is a factor that influences prognosis. Lipidomics analysis of LSR-high-expressing gastric cancer cells revealed an increase in β-oxidation. Based on these results, we used etomoxir, a β-oxidation inhibitor, and found that it inhibited cell proliferation as well as the suppression of LSR. Similarly, in a mouse xenograft model of LSR-highly expressing gastric cancer cells, the tumor growth effect of high-fat diet feeding was counteracted by etomoxir, consistent with the Ki-67 labeling index.

Conclusions

We demonstrated that lipids are taken up into gastric cancer cells via LSR and cause an increase in β-oxidation, resulting in the promotion of cancer progression. Controlling LSR-mediated lipid metabolism may be a novel therapeutic strategy for gastric cancer.

背景溶脂刺激脂蛋白受体(LSR)是一种脂质受体,与癌症进展有关。然而,其对细胞内代谢的具体影响尚不清楚。我们的目的是阐明 LSR 介导的胃癌脂质代谢机制。方法我们研究了胃癌细胞中脂蛋白给药诱导的脂质代谢变化,并评估了胃癌患者 LSR 表达和脂滴形成的意义。结果在胃癌细胞中,LSR 促进了细胞对脂蛋白的吸收和细胞增殖。此外,在表达高水平 LSR 的胃癌细胞中抑制 LSR 可抵消这两种效应。对人类胃癌组织的免疫组化分析表明,通过 LSR 增加的脂滴是影响预后的一个因素。对高表达 LSR 的胃癌细胞进行的脂质组学分析表明,β-氧化增加。基于这些结果,我们使用了β-氧化抑制剂etomoxir,发现它不仅能抑制细胞增殖,还能抑制LSR。同样,在高表达 LSR 的胃癌细胞小鼠异种移植模型中,依托莫西尔抵消了高脂饮食喂养对肿瘤生长的影响,这与 Ki-67 标记指数一致。控制 LSR 介导的脂质代谢可能是治疗胃癌的一种新策略。
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引用次数: 0
Limitations of the cox proportional hazards model and alternative approaches in metachronous recurrence research 考克斯比例危险度模型的局限性以及近代复发研究中的替代方法
IF 7.4 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-09-16 DOI: 10.1007/s10120-024-01554-x
Lingyu Xu, Siqi Jiang, Tianyang Li, Yan Xu

The article by Shin et al. provides valuable insights into the correlation between the gastric mucosa-associated gastric microbiome (MAM) and metachronous recurrence. However, the use of the Cox proportional hazards model in their analysis presents several limitations. The study may result in mixed censoring outcomes, and the assumption of constant hazard ratios over time may not hold. Considering these limitations, future research should adopt alternative approaches, such as the accelerated failure time (AFT) model, to provide a more comprehensive understanding of the relationship between gastric MAM and metachronous recurrence.

Shin 等人的文章就胃黏膜相关胃微生物组(MAM)与远期复发之间的相关性提供了有价值的见解。然而,他们在分析中使用的 Cox 比例危险模型存在一些局限性。该研究可能会导致混合普查结果,而且随着时间推移危险比恒定的假设可能不成立。考虑到这些局限性,未来的研究应采用其他方法,如加速衰竭时间(AFT)模型,以更全面地了解胃癌 MAM 与远期复发之间的关系。
{"title":"Limitations of the cox proportional hazards model and alternative approaches in metachronous recurrence research","authors":"Lingyu Xu, Siqi Jiang, Tianyang Li, Yan Xu","doi":"10.1007/s10120-024-01554-x","DOIUrl":"https://doi.org/10.1007/s10120-024-01554-x","url":null,"abstract":"<p>The article by Shin et al. provides valuable insights into the correlation between the gastric mucosa-associated gastric microbiome (MAM) and metachronous recurrence. However, the use of the Cox proportional hazards model in their analysis presents several limitations. The study may result in mixed censoring outcomes, and the assumption of constant hazard ratios over time may not hold. Considering these limitations, future research should adopt alternative approaches, such as the accelerated failure time (AFT) model, to provide a more comprehensive understanding of the relationship between gastric MAM and metachronous recurrence.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252984","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}
引用次数: 0
Multitask machine learning-based tumor-associated collagen signatures predict peritoneal recurrence and disease-free survival in gastric cancer 基于多任务机器学习的肿瘤相关胶原蛋白特征可预测胃癌腹膜复发和无病生存期
IF 7.4 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-09-14 DOI: 10.1007/s10120-024-01551-0
Meiting Fu, Yuyu Lin, Junyao Yang, Jiaxin Cheng, Liyan Lin, Guangxing Wang, Chenyan Long, Shuoyu Xu, Jianping Lu, Guoxin Li, Jun Yan, Gang Chen, Shuangmu Zhuo, Dexin Chen

Background

Accurate prediction of peritoneal recurrence for gastric cancer (GC) is crucial in clinic. The collagen alterations in tumor microenvironment affect the migration and treatment response of cancer cells. Herein, we proposed multitask machine learning-based tumor-associated collagen signatures (TACS), which are composed of quantitative collagen features derived from multiphoton imaging, to simultaneously predict peritoneal recurrence (TACSPR) and disease-free survival (TACSDFS).

Methods

Among 713 consecutive patients, with 275 in training cohort, 222 patients in internal validation cohort, and 216 patients in external validation cohort, we developed and validated a multitask machine learning model for simultaneously predicting peritoneal recurrence (TACSPR) and disease-free survival (TACSDFS). The accuracy of the model for prediction of peritoneal recurrence and prognosis as well as its association with adjuvant chemotherapy were evaluated.

Results

The TACSPR and TACSDFS were independently associated with peritoneal recurrence and disease-free survival in three cohorts, respectively (all P < 0.001). The TACSPR demonstrated a favorable performance for peritoneal recurrence in all three cohorts. In addition, the TACSDFS also showed a satisfactory accuracy for disease-free survival among included patients. For stage II and III diseases, adjuvant chemotherapy improved the survival of patients with low TACSPR and low TACSDFS, or high TACSPR and low TACSDFS, or low TACSPR and high TACSDFS, but had no impact on patients with high TACSPR and high TACSDFS.

Conclusions

The multitask machine learning model allows accurate prediction of peritoneal recurrence and survival for GC and could distinguish patients who might benefit from adjuvant chemotherapy.

背景准确预测胃癌(GC)腹膜复发在临床上至关重要。肿瘤微环境中的胶原蛋白改变会影响癌细胞的迁移和治疗反应。在此,我们提出了基于多任务机器学习的肿瘤相关胶原特征(TACS),该特征由多光子成像得到的定量胶原特征组成,可同时预测腹膜复发(TACSPR)和无病生存(TACSDFS)。方法在713例连续患者(其中275例为训练队列,222例为内部验证队列,216例为外部验证队列)中,我们开发并验证了同时预测腹膜复发(TACSPR)和无病生存(TACSDFS)的多任务机器学习模型。结果在三个队列中,TACSPR 和 TACSDFS 分别与腹膜复发和无病生存率独立相关(均为 P <0.001)。在所有三个队列中,TACSPR 在腹膜复发方面表现良好。此外,TACSDFS 对纳入患者的无病生存率也显示出令人满意的准确性。对于II期和III期疾病,辅助化疗提高了低TACSPR和低TACSDFS、或高TACSPR和低TACSDFS、或低TACSPR和高TACSDFS患者的生存率,但对高TACSPR和高TACSDFS患者没有影响。
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引用次数: 0
期刊
Gastric Cancer
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