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A Standardized Pathology Report for Gastric Cancer: 2nd Edition. 胃癌标准化病理报告:第 2 版。
IF 3.2 4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2023-01-01 DOI: 10.5230/jgc.2023.23.e7
Young Soo Park, Myeong-Cherl Kook, Baek-Hui Kim, Hye Seung Lee, Dong-Wook Kang, Mi-Jin Gu, Ok Ran Shin, Younghee Choi, Wonae Lee, Hyunki Kim, In Hye Song, Kyoung-Mee Kim, Hee Sung Kim, Guhyun Kang, Do Youn Park, So-Young Jin, Joon Mee Kim, Yoon Jung Choi, Hee Kyung Chang, Soomin Ahn, Mee Soo Chang, Song-Hee Han, Yoonjin Kwak, An Na Seo, Sung Hak Lee, Mee-Yon Cho

The first edition of 'A Standardized Pathology Report for Gastric Cancer' was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

第一版《胃癌标准化病理报告》由韩国病理学家协会胃肠道病理研究小组发起,于 17 年前出版。从那时起,胃癌(GC)的病理诊断、分子遗传学和治疗取得了重大进展。为了反映这些变化,韩国病理学家学会胃肠道病理研究组成立了一个委员会,负责出版该报告的第二版。第二版由两部分组成:标准数据元素和条件数据元素。标准数据元素包含基本病理结果和预测 GC 患者预后所需的项目,足以满足常规外科病理服务的需要。与辅助治疗相关的其他诊断和预后因素(包括分子生物标记物)被归类为条件数据元素,以便每位病理学家根据自己所在机构的环境选择合适的项目。我们相信,标准化病理报告将有助于 GC 诊断,并促进大规模多学科合作研究。
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引用次数: 0
Breakthroughs in the Systemic Treatment of HER2-Positive Advanced/Metastatic Gastric Cancer: From Singlet Chemotherapy to Triple Combination. HER2阳性晚期/转移性胃癌系统治疗的突破:从单一化疗到三联化疗。
IF 3.2 4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2023-01-01 DOI: 10.5230/jgc.2023.23.e6
Sun Young Rha, Hyun Cheol Chung

Gastric cancer is heterogeneous in morphology, biology, genomics, and treatment response. Alterations in human epidermal growth factor receptor 2 (HER2) overexpression, microsatellite instability (MSI) status, programmed death-ligand 1 (PD-L1) levels, and fibroblast growth factor receptor 2 (FGFR2) can be used as biomarkers. Since the combination of fluoropyrimidine/platinum plus trastuzumab that was investigated in the ToGA trial was approved as a standard of care in HER2-positive patients in 2010, no other agents showed efficacy in the first- (HELOISE, LOGiC, JACOB trials) and second- (TyTAN, GATSBY, T-ACT trials) line treatments. Despite the success in treating breast cancer, various anti-HER2 agents, including a monoclonal antibody (pertuzumab), an antibody-drug conjugate (ADC; trastuzumab emtansine [T-DM1]), and a small molecule (lapatinib) failed to translate into clinical benefits until the KEYNOTE-811 (first-line) and DESTINY-Gastri01 (≥second-line) trials were conducted. The incorporation of HER2-directed treatment with immune checkpoint inhibitors in the form of a monoclonal antibody or ADC is now approved as a standard treatment. Despite the promising results of new agents (engineered monoclonal antibodies, bi-specific antibodies, fusion proteins, and small molecules) in the early phase of development, the management of HER2-positive gastric cancer requires further optimization to achieve precision medicine with a chemotherapeutic backbone. Treatment resistance is a complex process that can be overcome using a combination of chemotherapy, targeted agents, and immune checkpoint inhibitors, including novel agents. HER2 status must be reassessed in patients undergoing anti-HER2 treatment with disease progression after the first-line treatment. As a general guideline, patients who need systemic treatment should receive chemotherapy plus targeted agents, anti-angiogenic agents, immune checkpoint inhibitors, or their combinations.

胃癌在形态学、生物学、基因组学和治疗反应方面具有异质性。人表皮生长因子受体 2 (HER2) 过表达、微卫星不稳定性 (MSI) 状态、程序性死亡配体 1 (PD-L1) 水平和成纤维细胞生长因子受体 2 (FGFR2) 的变化可作为生物标记物。自 2010 年 ToGA 试验中研究的氟嘧啶/铂联合曲妥珠单抗被批准作为 HER2 阳性患者的标准治疗方案后,在一线(HELOISE、LOGiC、JACOB 试验)和二线(TyTAN、GATSBY、T-ACT 试验)治疗中,没有其他药物显示出疗效。尽管在治疗乳腺癌方面取得了成功,但包括单克隆抗体(pertuzumab)、抗体药物共轭物(ADC;曲妥珠单抗 emtansine [T-DM1])和小分子药物(拉帕替尼)在内的各种抗 HER2 药物在 KEYNOTE-811(一线)和 DESTINY-Gastri01(≥二线)试验之前都未能转化为临床疗效。目前,以单克隆抗体或 ADC 形式将 HER2 定向治疗与免疫检查点抑制剂相结合已被批准为标准治疗方法。尽管新药(工程化单克隆抗体、双特异性抗体、融合蛋白和小分子药物)在早期开发阶段取得了可喜的成果,但 HER2 阳性胃癌的治疗仍需进一步优化,以实现以化疗为骨干的精准医疗。耐药性是一个复杂的过程,可以通过化疗、靶向药物和免疫检查点抑制剂(包括新型药物)的联合使用来克服。接受抗 HER2 治疗的患者在一线治疗后疾病进展,必须重新评估 HER2 状态。一般来说,需要接受全身治疗的患者应接受化疗加靶向药物、抗血管生成药物、免疫检查点抑制剂或其组合治疗。
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引用次数: 0
Impact of the COVID-19 Pandemic on Gastric Cancer Screening in South Korea: Results From the Korean National Cancer Screening Survey (2017-2021). COVID-19 大流行对韩国胃癌筛查的影响:韩国全国癌症筛查调查(2017-2021 年)结果》。
IF 3.2 4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2022-10-01 DOI: 10.5230/jgc.2022.22.e36
Kyeongmin Lee, Mina Suh, Jae Kwan Jun, Kui Son Choi

Purpose: The coronavirus disease 2019 (COVID-19) pandemic has significantly disrupted cancer screening services worldwide. We aimed to measure the impact of COVID-19 on gastric cancer screening rates based on age, sex, household income, and residential area.

Materials and methods: We analyzed data from the Korean National Cancer Screening Survey from 2017 to 2021 for adults aged 40-74 years. We evaluated the gastric cancer screening rate within two years in accordance with the National Cancer Screening Program protocol recommendations and that within the previous year. We compared the trends in the pre- and post-COVID-19 outbreak periods.

Results: Before the COVID-19 outbreak, there was little change in the gastric cancer screening rates until 2019. After the COVID-19 outbreak, the screening rate as per recommendation decreased from 70.8% in 2019 to 68.9% in 2020 and that for one year decreased from 32.7% in 2019 to 27.2% in 2020. However, as the COVID-19 pandemic continued after 2020, both gastric cancer screening rates as per recommendations and for one year rebounded. Although a similar trend was observed for the upper endoscopy screening rate, the upper gastrointestinal series screening rate decreased from 7.8% in 2020 to 3.1% in 2021. During the pandemic, the screening rate decreased among younger adults (40-49), those residing in metropolitan regions, and those with high incomes.

Conclusions: Despite a decline in gastric cancer screening rate during the COVID-19 pandemic, the rate surged in 2021. Further studies are needed to estimate the impact of cancer screening delays on future cancer-related mortalities.

目的:冠状病毒病 2019(COVID-19)大流行严重扰乱了全球癌症筛查服务。我们的目的是根据年龄、性别、家庭收入和居住地区来衡量 COVID-19 对胃癌筛查率的影响:我们分析了 2017 年至 2021 年韩国全国癌症筛查调查中 40-74 岁成人的数据。我们根据国家癌症筛查计划的建议,对两年内的胃癌筛查率和上一年的胃癌筛查率进行了评估。我们比较了 COVID-19 爆发前后的趋势:结果:在 COVID-19 爆发之前,胃癌筛查率在 2019 年之前几乎没有变化。COVID-19 爆发后,根据推荐的筛查率从 2019 年的 70.8% 降至 2020 年的 68.9%,一年的筛查率从 2019 年的 32.7% 降至 2020 年的 27.2%。然而,随着 COVID-19 在 2020 年后继续流行,按建议筛查率和一年胃癌筛查率均有所回升。虽然上消化道内镜筛查率也出现了类似的趋势,但上消化道系列筛查率却从 2020 年的 7.8% 降至 2021 年的 3.1%。在大流行期间,年轻成年人(40-49 岁)、居住在大都市地区和高收入人群的筛查率有所下降:结论:尽管在 COVID-19 大流行期间胃癌筛查率有所下降,但 2021 年胃癌筛查率激增。需要进一步开展研究,估算癌症筛查延迟对未来癌症相关死亡率的影响。
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引用次数: 0
Endoscopic Findings and Treatment of Gastric Neoplasms in Familial Adenomatous Polyposis. 家族性腺瘤性息肉病胃肿瘤的内镜表现和治疗。
IF 2.5 4区 医学 Q2 Medicine Pub Date : 2022-10-01 DOI: 10.5230/jgc.2022.22.e30
Chihiro Sato, Kazuya Takahashi, Hiroki Sato, Takumi Naruse, Nao Nakajima, Masafumi Takatsuna, Ken-Ichi Mizuno, Satoru Hashimoto, Manabu Takeuchi, Junji Yokoyama, Masaaki Kobayashi, Shuji Terai

Purpose: Gastric neoplasia is a common manifestation of familial adenomatous polyposis (FAP). This study aimed to elucidate the clinical characteristics, endoscopic features including fundic gland polyposis (FGPsis), and treatment outcomes of gastric neoplasms (GNs) in patients with FAP.

Materials and methods: A total of 35 patients diagnosed with FAP, including nine patients from four pedigrees who underwent esophagogastroduodenoscopy (EGD), were investigated regarding patient characteristics, GN morphology, and treatment outcomes.

Results: Twenty-one patients (60.0%) had 38 GNs; 33 (86.8%) and 5 (13.2%) were histologically diagnosed with adenocarcinoma and adenoma, respectively. There were no specific patient characteristics related to GNs. Nodule-type GNs were more prevalent in patients with FGP than without (52.2% vs. 0.0%, P=0.002) in the upper body of the stomach. Conversely, depressed-type GNs were fewer in patients with FGPsis than in those without (13.0% vs. 73.3%, P<0.001). Slightly elevated-type GNs were observed in both groups (34.8% vs. 20.0%, P=0.538). Even within pedigrees, the background gastric mucosa and types of GNs varied. In total, 24 GNs were treated with endoscopic submucosal dissection (ESD) and eight with endoscopic mucosal resection (EMR). EMR was selected for GNs with FGPsis because of the technical difficulty of ESD, resulting in a lower en bloc resection rate (62.5% vs. 100%, P=0.014).

Conclusions: Our study indicates the necessity of routine EGD surveillance in patients diagnosed with FAP. Notably, the morphology and location of GNs differed between patients with and without FGPsis. Endoscopic treatment and outcomes require more attention in cases of FGPsis.

目的:胃瘤变是家族性腺瘤性息肉病(FAP)的常见表现。本研究旨在阐明FAP患者胃肿瘤(GNs)的临床特征、内镜特征(包括基底腺息肉病(FGPsis))和治疗结果。材料和方法:共35例确诊为FAP的患者,其中9例来自4个家系,均行食管胃十二指肠镜检查(EGD),研究患者特征、GN形态和治疗结果。结果:21例(60.0%)患者有38个GNs;组织学诊断为腺癌33例(86.8%),腺瘤5例(13.2%)。没有与GNs相关的特定患者特征。结节型GNs在FGP患者中较无FGP患者更为普遍(52.2%比0.0%,P=0.002)。相反,FGPsis患者的抑郁型gn少于非FGPsis患者(13.0% vs. 73.3%)。结论:我们的研究表明,FAP患者有必要进行常规EGD监测。值得注意的是,GNs的形态和位置在FGPsis患者和非FGPsis患者之间存在差异。FGPsis病例的内镜治疗和结果需要更多的关注。
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引用次数: 1
Extragastric Metastasis of Early Gastric Cancer After Endoscopic Submucosal Dissection With Lymphovascular Invasion and Negative Resected Margins. 内镜下粘膜下剥离伴淋巴血管浸润及切除边缘阴性后早期胃癌胃外转移。
IF 2.5 4区 医学 Q2 Medicine Pub Date : 2022-10-01 DOI: 10.5230/jgc.2022.22.e27
Han Myung Lee, Yoonjin Kwak, Hyunsoo Chung, Sang Gyun Kim, Soo-Jeong Cho

Purpose: Lymphovascular invasion is a criterion for non-curative resection in patients who have undergone endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). We aimed to determine the rate of extragastric metastasis (EGM) and identify the predictors of EGM in patients with negative resection margins (R0 resection) and lymphovascular invasion in post-ESD pathology.

Materials and methods: A total of 2,983 patients underwent ESD for EGC. Among them, 110 had a pathology of R0 resection and positive lymphovascular invasion. Patients underwent additional gastrectomy (n=63) or further follow-up without gastrectomy (n=47).

Results: The 110 patients were assigned to one of the 3 groups according to ESD indications based on post-ESD pathology. The first group satisfied the absolute indication for ESD (n=18), the second group satisfied the expanded indications for ESD (n=34), and the last group satisfied the beyond indication (n=58). The number of occurrences of EGM in each group was 1 (5.6%), 3 (8.8%), and 3 (5.2%), respectively. The logistic regression analysis adjusted for age, sex, tumor size, and indication for ESD, showed that larger tumor size was associated with EGM (odds ratio, 1.76; 95% confidence interval, 1.00-3.10; P=0.048). In contrast, ESD indication criteria did not affect EGM (P=0.349).

Conclusions: Tumor size was the only predictive indicator for EGM in patients who underwent R0 resection and lymphovascular invasion on post-ESD pathology. Even patients with pathology corresponding to the absolute indication criteria of ESD had lymphovascular invasion, which means that they require additional gastrectomy due to the risk of EGM.

目的:淋巴血管侵犯是早期胃癌(EGC)行内镜下粘膜下剥离(ESD)患者进行非治愈性切除的标准。我们的目的是确定胃外转移(EGM)的发生率,并确定EGM的预测因素在阴性切除边缘(R0切除)和淋巴血管侵袭的患者在esd后病理。材料与方法:2983例EGC患者行ESD治疗。其中110例病理为R0切除,淋巴血管浸润阳性。患者接受了额外的胃切除术(n=63)或进一步随访而不进行胃切除术(n=47)。结果:110例患者根据ESD后病理情况,根据ESD适应症分为3组。第一组满足ESD绝对指征(n=18),第二组满足ESD扩展指征(n=34),最后一组满足ESD超越指征(n=58)。各组EGM发生率分别为1例(5.6%)、3例(8.8%)、3例(5.2%)。经年龄、性别、肿瘤大小和ESD适应症校正后的logistic回归分析显示,肿瘤大小越大与EGM相关(优势比为1.76;95%置信区间为1.00-3.10;P = 0.048)。而ESD指征标准对EGM无影响(P=0.349)。结论:肿瘤大小是esd后病理上行R0切除术和淋巴血管侵犯患者EGM的唯一预测指标。即使病理符合ESD绝对指征标准的患者也存在淋巴血管侵犯,这意味着由于EGM的风险,他们需要额外的胃切除术。
{"title":"Extragastric Metastasis of Early Gastric Cancer After Endoscopic Submucosal Dissection With Lymphovascular Invasion and Negative Resected Margins.","authors":"Han Myung Lee,&nbsp;Yoonjin Kwak,&nbsp;Hyunsoo Chung,&nbsp;Sang Gyun Kim,&nbsp;Soo-Jeong Cho","doi":"10.5230/jgc.2022.22.e27","DOIUrl":"https://doi.org/10.5230/jgc.2022.22.e27","url":null,"abstract":"<p><strong>Purpose: </strong>Lymphovascular invasion is a criterion for non-curative resection in patients who have undergone endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). We aimed to determine the rate of extragastric metastasis (EGM) and identify the predictors of EGM in patients with negative resection margins (R0 resection) and lymphovascular invasion in post-ESD pathology.</p><p><strong>Materials and methods: </strong>A total of 2,983 patients underwent ESD for EGC. Among them, 110 had a pathology of R0 resection and positive lymphovascular invasion. Patients underwent additional gastrectomy (n=63) or further follow-up without gastrectomy (n=47).</p><p><strong>Results: </strong>The 110 patients were assigned to one of the 3 groups according to ESD indications based on post-ESD pathology. The first group satisfied the absolute indication for ESD (n=18), the second group satisfied the expanded indications for ESD (n=34), and the last group satisfied the beyond indication (n=58). The number of occurrences of EGM in each group was 1 (5.6%), 3 (8.8%), and 3 (5.2%), respectively. The logistic regression analysis adjusted for age, sex, tumor size, and indication for ESD, showed that larger tumor size was associated with EGM (odds ratio, 1.76; 95% confidence interval, 1.00-3.10; P=0.048). In contrast, ESD indication criteria did not affect EGM (P=0.349).</p><p><strong>Conclusions: </strong>Tumor size was the only predictive indicator for EGM in patients who underwent R0 resection and lymphovascular invasion on post-ESD pathology. Even patients with pathology corresponding to the absolute indication criteria of ESD had lymphovascular invasion, which means that they require additional gastrectomy due to the risk of EGM.</p>","PeriodicalId":56072,"journal":{"name":"Journal of Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/be/64/jgc-22-339.PMC9633933.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40657422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Urinary Biomarkers for the Noninvasive Detection of Gastric Cancer. 尿液生物标志物在胃癌无创检测中的应用。
IF 2.5 4区 医学 Q2 Medicine Pub Date : 2022-10-01 DOI: 10.5230/jgc.2022.22.e28
Dehong Li, Li Yan, Fugui Lin, Xiumei Yuan, Xingwen Yang, Xiaoyan Yang, Lianhua Wei, Yang Yang, Yan Lu

Gastric cancer (GC) is associated with high morbidity and mortality rates. Thus, early diagnosis is important to improve disease prognosis. Endoscopic assessment represents the most reliable imaging method for GC diagnosis; however, it is semi-invasive and costly and heavily depends on the skills of the endoscopist, which limit its clinical applicability. Therefore, the search for new sensitive biomarkers for the early detection of GC using noninvasive sampling collection methods has attracted much attention among scientists. Urine is considered an ideal biofluid, as it is readily accessible, less complex, and relatively stable than plasma and serum. Over the years, substantial progress has been made in screening for potential urinary biomarkers for GC. This review explores the possible applications and limitations of urinary biomarkers in GC detection and diagnosis.

胃癌(GC)具有较高的发病率和死亡率。因此,早期诊断对改善疾病预后具有重要意义。内镜评估是诊断胃癌最可靠的影像学方法;然而,它是半侵入性和昂贵的,严重依赖于内窥镜医师的技能,这限制了它的临床适用性。因此,寻找新的灵敏的生物标志物,利用无创取样采集方法进行GC的早期检测,受到了科学家们的广泛关注。尿液被认为是一种理想的生物液体,因为它比血浆和血清容易获得,不那么复杂,而且相对稳定。多年来,在筛选潜在的GC尿液生物标志物方面取得了实质性进展。本文综述了尿液生物标志物在气相色谱检测和诊断中的应用前景及局限性。
{"title":"Urinary Biomarkers for the Noninvasive Detection of Gastric Cancer.","authors":"Dehong Li,&nbsp;Li Yan,&nbsp;Fugui Lin,&nbsp;Xiumei Yuan,&nbsp;Xingwen Yang,&nbsp;Xiaoyan Yang,&nbsp;Lianhua Wei,&nbsp;Yang Yang,&nbsp;Yan Lu","doi":"10.5230/jgc.2022.22.e28","DOIUrl":"https://doi.org/10.5230/jgc.2022.22.e28","url":null,"abstract":"<p><p>Gastric cancer (GC) is associated with high morbidity and mortality rates. Thus, early diagnosis is important to improve disease prognosis. Endoscopic assessment represents the most reliable imaging method for GC diagnosis; however, it is semi-invasive and costly and heavily depends on the skills of the endoscopist, which limit its clinical applicability. Therefore, the search for new sensitive biomarkers for the early detection of GC using noninvasive sampling collection methods has attracted much attention among scientists. Urine is considered an ideal biofluid, as it is readily accessible, less complex, and relatively stable than plasma and serum. Over the years, substantial progress has been made in screening for potential urinary biomarkers for GC. This review explores the possible applications and limitations of urinary biomarkers in GC detection and diagnosis.</p>","PeriodicalId":56072,"journal":{"name":"Journal of Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9c/a4/jgc-22-306.PMC9633929.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40657420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Molecular Pathology of Gastric Cancer. 胃癌的分子病理学。
IF 2.5 4区 医学 Q2 Medicine Pub Date : 2022-10-01 DOI: 10.5230/jgc.2022.22.e35
Moonsik Kim, An Na Seo

Gastric cancer (GC) is one of the most common lethal malignant neoplasms worldwide, with limited treatment options for both locally advanced and/or metastatic conditions, resulting in a dismal prognosis. Although the widely used morphological classifications may be helpful for endoscopic or surgical treatment choices, they are still insufficient to guide precise and/or personalized therapy for individual patients. Recent advances in genomic technology and high-throughput analysis may improve the understanding of molecular pathways associated with GC pathogenesis and aid in the classification of GC at the molecular level. Advances in next-generation sequencing have enabled the identification of several genetic alterations through single experiments. Thus, understanding the driver alterations involved in gastric carcinogenesis has become increasingly important because it can aid in the discovery of potential biomarkers and therapeutic targets. In this article, we review the molecular classifications of GC, focusing on The Cancer Genome Atlas (TCGA) classification. We further describe the currently available biomarker-targeted therapies and potential biomarker-guided therapies. This review will help clinicians by providing an inclusive understanding of the molecular pathology of GC and may assist in selecting the best treatment approaches for patients with GC.

胃癌(GC)是世界范围内最常见的致死性恶性肿瘤之一,对于局部晚期和/或转移性疾病的治疗选择有限,导致预后不佳。尽管广泛使用的形态学分类可能有助于内镜或手术治疗的选择,但它们仍然不足以指导个体患者的精确和/或个性化治疗。基因组技术和高通量分析的最新进展可能会提高对胃癌发病机制相关分子途径的理解,并有助于在分子水平上对胃癌进行分类。新一代测序技术的进步使得通过单个实验就能识别出几种基因改变。因此,了解胃癌发生的驱动改变变得越来越重要,因为它可以帮助发现潜在的生物标志物和治疗靶点。本文综述了胃癌的分子分类,重点介绍了肿瘤基因组图谱(TCGA)分类。我们进一步描述了目前可用的生物标志物靶向治疗和潜在的生物标志物引导治疗。这篇综述将帮助临床医生对胃癌的分子病理学有一个全面的了解,并有助于为胃癌患者选择最佳的治疗方法。
{"title":"Molecular Pathology of Gastric Cancer.","authors":"Moonsik Kim,&nbsp;An Na Seo","doi":"10.5230/jgc.2022.22.e35","DOIUrl":"https://doi.org/10.5230/jgc.2022.22.e35","url":null,"abstract":"<p><p>Gastric cancer (GC) is one of the most common lethal malignant neoplasms worldwide, with limited treatment options for both locally advanced and/or metastatic conditions, resulting in a dismal prognosis. Although the widely used morphological classifications may be helpful for endoscopic or surgical treatment choices, they are still insufficient to guide precise and/or personalized therapy for individual patients. Recent advances in genomic technology and high-throughput analysis may improve the understanding of molecular pathways associated with GC pathogenesis and aid in the classification of GC at the molecular level. Advances in next-generation sequencing have enabled the identification of several genetic alterations through single experiments. Thus, understanding the driver alterations involved in gastric carcinogenesis has become increasingly important because it can aid in the discovery of potential biomarkers and therapeutic targets. In this article, we review the molecular classifications of GC, focusing on The Cancer Genome Atlas (TCGA) classification. We further describe the currently available biomarker-targeted therapies and potential biomarker-guided therapies. This review will help clinicians by providing an inclusive understanding of the molecular pathology of GC and may assist in selecting the best treatment approaches for patients with GC.</p>","PeriodicalId":56072,"journal":{"name":"Journal of Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/65/1f/jgc-22-273.PMC9633931.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40657423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
PLK2 Single Nucleotide Variant in Gastric Cancer Patients Affects miR-23b-5p Binding. 胃癌患者PLK2单核苷酸变异影响miR-23b-5p结合
IF 2.5 4区 医学 Q2 Medicine Pub Date : 2022-10-01 DOI: 10.5230/jgc.2022.22.e31
Pia Pužar Dominkuš, Aner Mesic, Petra Hudler

Purpose: Chromosomal instability is a hallmark of gastric cancer (GC). It can be driven by single nucleotide variants (SNVs) in cell cycle genes. We investigated the associations between SNVs in candidate genes, PLK2, PLK3, and ATM, and GC risk and clinicopathological features.

Materials and methods: The genotyping study included 542 patients with GC and healthy controls. Generalized linear models were used for the risk and clinicopathological association analyses. Survival analysis was performed using the Kaplan-Meier method. The binding of candidate miRs was analyzed using a luciferase reporter assay.

Results: The PLK2 Crs15009-Crs963615 haplotype was under-represented in the GC group compared to that in the control group (Pcorr=0.050). Male patients with the PLK2 rs963615 CT genotype had a lower risk of GC, whereas female patients had a higher risk (P=0.023; P=0.026). The PLK2 rs963615 CT genotype was associated with the absence of vascular invasion (P=0.012). The PLK3 rs12404160 AA genotype was associated with a higher risk of GC in the male population (P=0.015). The ATM Trs228589-Ars189037-Grs4585 haplotype was associated with a higher risk of GC (P<0.001). The ATM rs228589, rs189037, and rs4585 genotypes TA+AA, AG+GG, and TG+GG were associated with the absence of perineural invasion (P=0.034). In vitro analysis showed that the cancer-associated miR-23b-5p mimic specifically bound to the PLK2 rs15009 G allele (P=0.0097). Moreover, low miR-23b expression predicted longer 10-year survival (P=0.0066) in patients with GC.

Conclusions: PLK2, PLK3, and ATM SNVs could potentially be helpful for the prediction of GC risk and clinicopathological features. PLK2 rs15009 affects the binding of miR-23b-5p. MiR-23b-5p expression status could serve as a prognostic marker for survival in patients with GC.

目的:染色体不稳定性是胃癌(GC)的标志。它可以由细胞周期基因中的单核苷酸变异(snv)驱动。我们研究了候选基因、PLK2、PLK3和ATM的SNVs与GC风险和临床病理特征之间的关系。材料与方法:对542例胃癌患者和健康对照进行基因分型研究。采用广义线性模型进行风险和临床病理关联分析。采用Kaplan-Meier法进行生存分析。使用荧光素酶报告基因试验分析候选mir的结合。结果:与对照组相比,GC组PLK2 Crs15009-Crs963615单倍型代表性不足(Pcorr=0.050)。PLK2 rs963615 CT基因型男性患者发生GC的风险较低,而女性患者发生GC的风险较高(P=0.023;P = 0.026)。PLK2 rs963615 CT基因型与无血管侵犯相关(P=0.012)。PLK3 rs12404160 AA基因型与男性人群中较高的GC风险相关(P=0.015)。ATM Trs228589-Ars189037-Grs4585单倍型与较高的GC风险相关(PATM rs228589、rs189037和rs4585基因型TA+AA、AG+GG和TG+GG与不存在神经周围侵犯相关(P=0.034)。体外分析显示,癌症相关的miR-23b-5p模拟物特异性结合PLK2 rs15009g等位基因(P=0.0097)。此外,低miR-23b表达预测GC患者10年生存率更长(P=0.0066)。结论:PLK2、PLK3和ATM snv可能有助于预测胃癌风险和临床病理特征。PLK2 rs15009影响miR-23b-5p的结合。MiR-23b-5p表达状态可作为胃癌患者生存的预后指标。
{"title":"<i>PLK2</i> Single Nucleotide Variant in Gastric Cancer Patients Affects miR-23b-5p Binding.","authors":"Pia Pužar Dominkuš,&nbsp;Aner Mesic,&nbsp;Petra Hudler","doi":"10.5230/jgc.2022.22.e31","DOIUrl":"https://doi.org/10.5230/jgc.2022.22.e31","url":null,"abstract":"<p><strong>Purpose: </strong>Chromosomal instability is a hallmark of gastric cancer (GC). It can be driven by single nucleotide variants (SNVs) in cell cycle genes. We investigated the associations between SNVs in candidate genes, <i>PLK2</i>, <i>PLK3</i>, and <i>ATM,</i> and GC risk and clinicopathological features.</p><p><strong>Materials and methods: </strong>The genotyping study included 542 patients with GC and healthy controls. Generalized linear models were used for the risk and clinicopathological association analyses. Survival analysis was performed using the Kaplan-Meier method. The binding of candidate miRs was analyzed using a luciferase reporter assay.</p><p><strong>Results: </strong>The <i>PLK2</i> <b>C</b><sub>rs15009</sub>-<b>C</b><sub>rs963615</sub> haplotype was under-represented in the GC group compared to that in the control group (P<sub>corr</sub>=0.050). Male patients with <i>the PLK2</i> rs963615 CT genotype had a lower risk of GC, whereas female patients had a higher risk (P=0.023; P=0.026). The <i>PLK2</i> rs963615 CT genotype was associated with the absence of vascular invasion (P=0.012). The <i>PLK3</i> rs12404160 AA genotype was associated with a higher risk of GC in the male population (P=0.015). The <i>ATM</i> <b>T</b><sub>rs228589</sub>-<b>A</b><sub>rs189037</sub>-<b>G</b><sub>rs4585</sub> haplotype was associated with a higher risk of GC (P<0.001). The <i>ATM</i> rs228589, rs189037, and rs4585 genotypes TA+AA, AG+GG, and TG+GG were associated with the absence of perineural invasion (P=0.034). <i>In vitro</i> analysis showed that the cancer-associated miR-23b-5p mimic specifically bound to <i>the PLK2</i> rs15009 G allele (P=0.0097). Moreover, low miR-23b expression predicted longer 10-year survival (P=0.0066) in patients with GC.</p><p><strong>Conclusions: </strong><i>PLK2</i>, <i>PLK3</i>, and <i>ATM</i> SNVs could potentially be helpful for the prediction of GC risk and clinicopathological features. <i>PLK2</i> rs15009 affects the binding of miR-23b-5p. MiR-23b-5p expression status could serve as a prognostic marker for survival in patients with GC.</p>","PeriodicalId":56072,"journal":{"name":"Journal of Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/66/57/jgc-22-348.PMC9633926.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40657425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Apatinib as a Third-Line Treatment for HER2-Positive Metastatic Gastric Cancer: A Multi-Center Single-Arm Cohort Study. 阿帕替尼作为her2阳性转移性胃癌的三线治疗:一项多中心单组队列研究
IF 2.5 4区 医学 Q2 Medicine Pub Date : 2022-10-01 DOI: 10.5230/jgc.2022.22.e33
Xin Zhang, Haoran Huo, Yanan Nie, Jiadong Xue, Zengjiang Yuan, Zhenyi Zhang

Purpose: Treatment options are limited after the failure of first-and second-line treatments in patients with HER2+ metastatic gastric cancer (mGC). The present study aimed to explore the efficacy, safety, and prognostic factors of apatinib efficacy as a third-line therapy for patients with human epithelial growth factor receptor 2-positive (HER2+) mGC.

Materials and methods: A total of 59 HER2+ mGC patients who received apatinib as third-line therapy were retrospectively enrolled in this two-center, single-arm, cohort study; the clinical response, survival data, and adverse events were retrieved.

Results: The median progression-free survival (PFS) was 5.2 months (95% confidence interval [CI], 3.9-6.5), and the median overall survival (OS) was 8.2 months (95% CI, 6.6-9.8) Furthermore, forward stepwise multivariate Cox regression analysis showed that a higher Eastern Cooperative Oncology Group performance status score and multiple metastases were independently correlated with decreased PFS and OS (both P<0.05). The main adverse events were leukopenia (45.8%), hypertension (44.1%), thrombocytopenia (39.0%), hand-foot syndrome (37.3%), and elevated transaminase (33.9%). Grade 3 adverse events mainly included hypertension (5.1%) and neutropenia (5.1%); grade 4 adverse events did not occur.

Conclusions: Apatinib is efficient and well tolerated in patients with HER2+ mGC as a third-line treatment, suggesting that it may be a candidate of choice for these patients.

目的:HER2+转移性胃癌(mGC)患者一线和二线治疗失败后,治疗选择有限。本研究旨在探讨阿帕替尼作为人上皮生长因子受体2阳性(HER2+) mGC患者三线治疗的疗效、安全性和预后因素。材料和方法:共有59例接受阿帕替尼作为三线治疗的HER2+ mGC患者回顾性纳入了这项双中心、单臂、队列研究;检索临床反应、生存数据和不良事件。结果:中位无进展生存期(PFS)为5.2个月(95%可信区间[CI], 3.9-6.5),中位总生存期(OS)为8.2个月(95% CI, 6.6-9.8)。此外,正向逐步多因素Cox回归分析显示,较高的东部肿瘤合作组表现状态评分和多发转移与PFS和OS的降低独立相关(均为PFS)。阿帕替尼在HER2+ mGC患者中作为三线治疗有效且耐受性良好,这表明它可能是这些患者的候选选择。
{"title":"Apatinib as a Third-Line Treatment for HER2-Positive Metastatic Gastric Cancer: A Multi-Center Single-Arm Cohort Study.","authors":"Xin Zhang,&nbsp;Haoran Huo,&nbsp;Yanan Nie,&nbsp;Jiadong Xue,&nbsp;Zengjiang Yuan,&nbsp;Zhenyi Zhang","doi":"10.5230/jgc.2022.22.e33","DOIUrl":"https://doi.org/10.5230/jgc.2022.22.e33","url":null,"abstract":"<p><strong>Purpose: </strong>Treatment options are limited after the failure of first-and second-line treatments in patients with HER2<sup>+</sup> metastatic gastric cancer (mGC). The present study aimed to explore the efficacy, safety, and prognostic factors of apatinib efficacy as a third-line therapy for patients with human epithelial growth factor receptor 2-positive (HER2<sup>+</sup>) mGC.</p><p><strong>Materials and methods: </strong>A total of 59 HER2<sup>+</sup> mGC patients who received apatinib as third-line therapy were retrospectively enrolled in this two-center, single-arm, cohort study; the clinical response, survival data, and adverse events were retrieved.</p><p><strong>Results: </strong>The median progression-free survival (PFS) was 5.2 months (95% confidence interval [CI], 3.9-6.5), and the median overall survival (OS) was 8.2 months (95% CI, 6.6-9.8) Furthermore, forward stepwise multivariate Cox regression analysis showed that a higher Eastern Cooperative Oncology Group performance status score and multiple metastases were independently correlated with decreased PFS and OS (both P<0.05). The main adverse events were leukopenia (45.8%), hypertension (44.1%), thrombocytopenia (39.0%), hand-foot syndrome (37.3%), and elevated transaminase (33.9%). Grade 3 adverse events mainly included hypertension (5.1%) and neutropenia (5.1%); grade 4 adverse events did not occur.</p><p><strong>Conclusions: </strong>Apatinib is efficient and well tolerated in patients with HER2<sup>+</sup> mGC as a third-line treatment, suggesting that it may be a candidate of choice for these patients.</p>","PeriodicalId":56072,"journal":{"name":"Journal of Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a2/01/jgc-22-408.PMC9633934.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40658920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Sp1-Induced SETDB1 Overexpression Transcriptionally Inhibits HPGD in a β-Catenin-Dependent Manner and Promotes the Proliferation and Metastasis of Gastric Cancer. sp1诱导的SETDB1过表达通过β- catenin依赖的方式转录抑制HPGD,促进胃癌的增殖和转移。
IF 2.5 4区 医学 Q2 Medicine Pub Date : 2022-10-01 DOI: 10.5230/jgc.2022.22.e26
Yaguan Fan, Libo Yang, Yi Ren, Yunhua Wu, Linhai Li, Lihua Li

Purpose: Gastric cancer (GC) has high morbidity and mortality, the cure rate of surgical treatment and drug chemotherapy is not ideal. Therefore, development of new treatment strategies is necessary. We aimed to identify the mechanism underlying Sp1 regulation of GC progression.

Methods and methods: The levels of Sp1, β-catenin, SET domain bifurcated 1 (SETDB1), and 15-hydroxyprostaglandin dehydrogenase (HPGD) were detected by quantitative reverse transcription polymerase chain reaction and western blot analysis. The targets of SETDB1 were predicted by AnimalTFDB, and dual-luciferase reporter assay was used for confirming the combination of Sp1, β-catenin, and SETDB1. HGC27 or AGS cells (1×106 cells/mouse) were injected into mice via the caudal vein for GC model establishment. The level of Ki67 was detected using immunohistochemistry, and hematoxylin and eosin staining was performed for evaluating tumor metastasis in mice with GC.

Results: HPGD was inhibited, while the protein levels of Sp1, β-catenin, and SETDB1 were up-regulated in GC tissues and cell lines. HPGD overexpression or SETDB1 silencing inhibited the proliferation, invasion, and migration of GC cells, and Sp1 regulated the proliferation, invasion, and migration of GC cells in a β-catenin-dependent manner. Furthermore, HPGD served as a target of SETDB1, and it was negatively regulated by SETDB1; additionally, Sp1 and β-catenin bound to the SETDB1 promoter and negatively regulated HPGD expression. We proved that Sp1 regulated GC progression via the SETDB1/HPGD axis.

Conclusions: Our findings revealed that Sp1 transcriptionally inhibited HPGD via SETDB1 in a β-catenin-dependent manner and promoted the proliferation and metastasis of GC cells.

目的:胃癌(GC)发病率和死亡率高,手术治疗和药物化疗治愈率不理想。因此,开发新的治疗策略是必要的。我们的目的是确定Sp1调控GC进展的机制。方法和方法:采用定量逆转录聚合酶链反应和western blot方法检测Sp1、β-catenin、SET结构域分叉1 (SETDB1)和15-羟基前列腺素脱氢酶(HPGD)水平。利用AnimalTFDB预测SETDB1的靶点,并利用双荧光素酶报告基因法确认Sp1、β-catenin和SETDB1的联合作用。经尾静脉注射HGC27或AGS细胞(1×106 cells/mouse)建立小鼠GC模型。免疫组化检测Ki67水平,苏木精和伊红染色评价胃癌小鼠肿瘤转移情况。结果:GC组织和细胞系中,HPGD受到抑制,Sp1、β-catenin、SETDB1蛋白水平上调。HPGD过表达或SETDB1沉默抑制GC细胞的增殖、侵袭和迁移,Sp1以β-catenin依赖的方式调节GC细胞的增殖、侵袭和迁移。此外,HPGD作为SETDB1的靶点,并受到SETDB1的负调控;此外,Sp1和β-catenin结合到SETDB1启动子上,负向调节HPGD的表达。我们证明Sp1通过SETDB1/HPGD轴调控GC进程。结论:Sp1以β-catenin依赖的方式通过SETDB1转录抑制HPGD,促进GC细胞的增殖和转移。
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引用次数: 2
期刊
Journal of Gastric Cancer
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