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Gastric Cáncer Molecular Classification

Izuma Nakayama, Eiji Shinozaki, Seiji Sakata, Noriko Yamamoto, Junko Fujisaki, Yusuke Muramatsu, Toru Hirota, Kengo Takeuchi, Shunji Takahashi, Kensei Yamaguchi, Tetsuo Noda
Gastric cancer in young adults has been pointed out to comprise a subgroup associated with distinctive clinicopathological features, including an equal gender distribution, advanced disease and diffuse-type histology. Comprehensive molecular analyses of gastric cancers have led to molecular-based classifications and to specific and effective treatment options available. The molecular traits of gastric cancers in young adults await investigations, which should provide a clue to explore therapeutic strategies...
February 16, 2019: Cancer Science
Shih-Chiang Huang, Kwai-Fong Ng, Ta-Sen Yeh, Chi-Tung Cheng, Jie-Sian Lin, Yu-Jen Liu, Huei-Chieh Chuang, Tse-Ching Chen
Limited studies investigated clinicopathological and prognostic significance of histologic and molecular subgroups of gastric cancer concurrently. We retrospectively enrolled 1,248 patients with gastric cancer who received radical gastrectomy with lymphadenectomy and classified these cases into the Epstein-Barr virus (EBV)-associated and microsatellite instability (MSI)-associated subtypes by EBV-encoded small RNA in situ hybridization and immunohistochemical stains for DNA mismatch repair proteins, respectively...
February 16, 2019: International Journal of Cancer. Journal International du Cancer
Jeeyun Lee, Ji Yeong An, Min Gew Choi, Se Hoon Park, Seung Tae Kim, Jun Ho Lee, Tae Sung Sohn, Jae Moon Bae, Sung Kim, Hyuk Lee, Byung-Hoon Min, Jae J Kim, Woo Kyoung Jeong, Dong-Il Choi, Kyoung-Mee Kim, Won Ki Kang, Mijung Kim, Sung Wook Seo
PURPOSE: Gastric cancer (GC) is the third-leading cause of cancer-related deaths. Several pivotal clinical trials of adjuvant treatments were performed during the previous decade; however, the optimal regimen for adjuvant treatment of GC remains controversial. PATIENTS AND METHODS: We developed a novel deep learning-based survival model (survival recurrent network [SRN]) in patients with GC by including all available clinical and pathologic data and treatment regimens...
December 2018: JCO Clinical Cancer Informatics
Hai Zhong, Xiang Li, Junhua Zhang, Xu Wu
BACKGROUND: Gastric tumors generally have a poor prognosis and molecular markers to improve early detection and predict outcomes are greatly needed. The present study reports that periostin (POSTN), a secretory protein that can alter the remodeling of the extracellular matrix, is highly expressed in gastric tumors. MATERIALS AND METHODS: Gastric tissues were collected from patients at the Department of Thoracic Surgery/Huiqiao Medical Center, Nanfang Hospital, Southern Medical University...
January 13, 2019: Journal of Cellular Biochemistry
David Vrána, Marcel Matzenauer, Čestmír Neoral, René Aujeský, Radek Vrba, Bohuslav Melichar, Nikol Rušarová, Marie Bartoušková, Janusz Jankowski
Esophageal and gastric cancers represent tumors with poor prognosis. Unfortunately, radiotherapy, chemotherapy, and targeted therapy have made only limited progress in recent years in improving the generally disappointing outcome. Immunotherapy with checkpoint inhibitors is a novel treatment approach that quickly entered clinical practice in malignant melanoma and renal cell cancer, but the role in esophageal and gastric cancer is still poorly defined. The principal prognostic/predictive biomarkers for immunotherapy efficacy currently considered are PD-L1 expression along with defects in mismatch repair genes resulting in microsatellite instability (MSI-H) phenotype...
December 20, 2018: International Journal of Molecular Sciences
Wenyi Luo, Faysal Fedda, Patrick Lynch, Dongfeng Tan
Gastric cancer, a group of common malignancies, results in the most cancer mortality worldwide after only lung and colorectal cancer. Although familial gastric cancers have long been recognized, it was not until recently that they were discovered to be associated with mutations of specific genes. Mutations of CDH1 , the gene encoding E-cadherin, are the most common germline mutations detected in gastric cancer and underlie hereditary diffuse gastric cancer (HDGC) syndrome. All reported HDGCs are the pure diffuse type by Lauren classification and are associated with dismal prognosis once the tumor invades the submucosa...
2018: Frontiers in Pharmacology
Kota Itahashi, Shunsuke Kondo, Takashi Kubo, Yutaka Fujiwara, Mamoru Kato, Hitoshi Ichikawa, Takahiko Koyama, Reitaro Tokumasu, Jia Xu, Claudia S Huettner, Vanessa V Michelini, Laxmi Parida, Takashi Kohno, Noboru Yamamoto
Background: Oncologists increasingly rely on clinical genome sequencing to pursue effective, molecularly targeted therapies. This study assesses the validity and utility of the artificial intelligence Watson for Genomics (WfG) for analyzing clinical sequencing results. Methods: This study identified patients with solid tumors who participated in in-house genome sequencing projects at a single cancer specialty hospital between April 2013 and October 2016. Targeted genome sequencing results of these patients' tumors, previously analyzed by multidisciplinary specialists at the hospital, were reanalyzed by WfG...
2018: Frontiers in Medicine
Qianchen Ma, Fei Yuan
As the perioperative chemotherapy and conversion therapy has been widely implemented on the standard treatment of gastric cancer patients, it is of great importance to evaluate the efficacy of these patients accurately by effective methods. Being an important grading standard for histomorphological evaluation of excision specimens after neoadjuvant chemotherapy, pathological tumor regression grade (TRG) system is mainly used to assess the degree of fibrosis of tumor tissue and the proportion of residual tumor cells...
October 25, 2018: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
Lingyu Sun
There are two major stage classification systems for gastric cancer: the tumor-node-metastasis (TNM) staging by the International Union against Cancer (UICC)/the American Joint Committee on Cancer(AJCC) and the Japanese Classification of Gastric Carcinoma by the Japanese Gastric Cancer Association(JGCA). The evolution of these two systems showed the advancement of gastric cancer treatment. The independence of TNM and JGCA staging system is not conducive to global communication and cooperation. The integration of 2010 Japan's 14th edition of the General Rules for Gastric Cancer Study and the 7th edition of UICC/AJCC TNM staging formed an internationally unified clinical staging system...
October 25, 2018: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
Kristy Lee, Kate Krempely, Maegan E Roberts, Michael J Anderson, Fatima Carneiro, Elizabeth Chao, Katherine Dixon, Joana Figueiredo, Rajarshi Ghosh, David Huntsman, Pardeep Kaurah, Chimene Kesserwan, Tyler Landrith, Shuwei Li, Arjen R Mensenkamp, Carla Oliveira, Carolina Pardo, Tina Pesaran, Matthew Richardson, Thomas P Slavin, Amanda B Spurdle, Mackenzie Trapp, Leora Witkowski, Charles S Yi, Liying Zhang, Sharon E Plon, Kasmintan A Schrader, Rachid Karam
The variant curation guidelines published in 2015 by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) provided the genetics community with a framework to assess variant pathogenicity; however, these rules are not gene specific. Germline pathogenic variants in the CDH1 gene cause hereditary diffuse gastric cancer and lobular breast cancer, a clinically challenging cancer predisposition syndrome that often requires a multidisciplinary team of experts to be properly managed...
November 2018: Human Mutation
Vivek Kumar, Parita Soni, Mohit Garg, Stephan Kamholz, Abhinav B Chandra
Globally, gastric malignancy contributes to significant cancer-related morbidity and mortality. Despite a recent approval of two targeted agents, trastuzumab and ramucirumab, the treatment options for advanced-stage gastric cancer are limited. Consequently, the overall clinical outcomes for patients with advanced-stage gastric cancer remain poor. Numerous agents that are active against novel targets have been evaluated in the course of randomized trials; however, most have produced disappointing results because of the molecular heterogeneity of gastric cancer...
2018: Frontiers in Pharmacology
Kejun Wang, Xin Duan, Feng Gao, Wei Wang, Liangliang Liu, Xin Wang
It is becoming increasingly clear that major malignancies such as breast, colorectal and gastric cancers are not single disease entities, but comprising multiple cancer subtypes of distinct molecular properties. Molecular subtyping has been widely used to dissect inter-tumor biological heterogeneity, in relation to clinical outcomes. A key step of this methodology is to perform unsupervised classification of gene expression profiles, which, however, often suffers challenges of high-dimensionality, feature redundancy as well as noise and irrelevant information...
2018: PloS One
Meng-Ting Lin, Hao-Jun Song, Xiao-Yun Ding
Gastric cancer (GC) is one of the most frequently diagnosed malignant diseases. The molecular mechanisms of metastasis remain unclear. Recently, studies have shown that long non-coding RNAs (lncRNAs) play critical roles in metastasis. Therefore, deeper understanding of this mechanism could provide potential diagnostic tools and therapeutic targets for metastatic GC. This review focuses on dysregulated lncRNAs in GC metastases. Due to the identification of multiple diverse mechanisms involved in GC metastasis, we classified them into seven categories, including lncRNAs related to epithelial-mesenchymal transition, regulation of degradation of extracellular matrix, angiopoiesis, vasculogenic mimicry, and immunologic escape...
September 7, 2018: World Journal of Gastroenterology: WJG
Cristina Díaz Del Arco, Lourdes Estrada Muñoz, Elena Molina Roldán, Mª Ángeles Cerón Nieto, Luis Ortega Medina, Soledad García Gómez de Las Heras, Mª Jesús Fernández Aceñero
Several classification systems have been described for stratifying patients with gastric carcinoma (GC). However, their prognostic value is low, and there is an urgent need for identification of molecular markers and development of new classifications. Retrospective study of 206 cases of GC diagnosed and surgically resected in our hospital between 2000 and 2017. Clinicopathological features of all cases were assessed and tissue microarrays were constructed for immunohistochemical (IHC) study. Patients were stratified based on IHC results...
December 2018: Virchows Archiv: An International Journal of Pathology
Bin Cao, Yu Zhao, Zheng Zhang, Hengcun Li, Jie Xing, Shuilong Guo, Xintao Qiu, Shutian Zhang, Li Min, Shengtao Zhu
Lauren classification is a pathology-based gastric cancer (GC) subtyping system, which is widely used in the clinical treatment of patients with GC. However, genome-scale molecular characteristics to distinguish between diffuse (DF) and intestinal (IT) GC remain incompletely characterized, particularly at the transcriptional regulatory level. In the present study, gene regulatory networks were constructed using the Passing Attributes between Networks for Data Assimilation (PANDA) algorithm for DF, IT and mixed GC...
November 2018: International Journal of Oncology
Helena Magalhães, Mário Fontes-Sousa, Manuela Machado
Gastric cancer (GC) remains a public health problem, being the fifth most common cancer worldwide. In the western countries, the majority of patients present with advanced disease. Additionally, 65 to 75% of patients treated with curative intent will relapse and develop systemic disease. In metastatic disease, systemic treatment still represents the state of the art, with less than a year of median overall survival. The new molecular classification of GC was published in 2014, identifying four distinct major subtypes of gastric cancer, and has encouraged the investigation of new and more personalized treatment strategies...
2018: Canadian Journal of Gastroenterology & Hepatology
Tasuku Matsuoka, Masakazu Yashiro
Gastric cancer (GC) is one of the most prevalent malignant types in the world and an aggressive disease with a poor 5-year survival. This cancer is biologically and genetically heterogeneous with a poorly understood carcinogenesis at the molecular level. Although the incidence is declining, the outcome of patients with GC remains dismal. Thus, the detection at an early stage utilizing useful screening approaches, selection of an appropriate treatment plan, and effective monitoring is pivotal to reduce GC mortalities...
July 14, 2018: World Journal of Gastroenterology: WJG
Francesca Battaglin, Madiha Naseem, Alberto Puccini, Heinz-Josef Lenz
Gastro-esophageal adenocarcinomas (GEA) represent a severe global health burden and despite improvements in the multimodality treatment of these malignancies the prognosis of patients remains poor. HER2 overexpression/amplification has been the first predictive biomarker approved in clinical practice to guide patient selection for targeted treatment with trastuzumab in advanced gastric and gastro-esophageal junction cancers. More recently, immunotherapy has been approved for the treatment of GEA and PD-L1 expression is now a biomarker required for the administration of pembrolizumab in these diseases...
2018: Cancer Cell International
Masashi Fukayama, Akiko Kunita, Atsushi Kaneda
Epstein-Barr virus-associated gastric cancer (EBVaGC) is a representative EBV-infected epithelial neoplasm, which is now included as one of the four subtypes of The Cancer Genome Atlas molecular classification of gastric cancer. In this review, we portray a gastritis-infection-cancer sequence of EBVaGC. This virus-associated type of gastric cancer demonstrates clonal growth of EBV-infected epithelial cells within the mucosa of atrophic gastritis. Its core molecular abnormality is the EBV-specific hyper-epigenotype of CpG island promoter methylation, which induces silencing of tumor suppressor genes...
2018: Advances in Experimental Medicine and Biology
Lara Alessandrini, Melissa Manchi, Valli De Re, Riccardo Dolcetti, Vincenzo Canzonieri
Gastric cancer (GC) is a common malignant neoplasm worldwide and one of the main cause of cancer-related deaths. Despite some advances in therapies, long-term survival of patients with advanced disease remains poor. Different types of classification have been used to stratify patients with GC for shaping prognosis and treatment planning. Based on new knowledge of molecular pathways associated with different aspect of GC, new pathogenetic classifications for GC have been and continue to be proposed. These novel classifications create a new paradigm in the definition of cancer biology and allow the identification of relevant GC genomic subsets by using different techniques such as genomic screenings, functional studies and molecular or epigenetic characterization...
June 6, 2018: International Journal of Molecular Sciences
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