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Cancers
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Molecular Mechanisms of Gastric Cancer Development
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Molecular Mechanisms of Gastric Cancer Development

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 11046

Special Issue Editor

Prof. Sung-Hsin Kuo

E-Mail Website
Guest Editor
1. Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
2. Graduate Institute of Oncology, National Taiwan University College of Medicine
Interests: lymphoma; translational research; radiation oncology; gastrointestinal cancer; breast cancer; tumor-stroma-communication; antiangiogenic therapy; tumor resistance

Special Issue Information

Dear Colleagues,

Gastric cancer, a heterogeneous disease, remains the most common cause of cancer-related mortality worldwide. Gastric cancers are divided into intestinal, diffuse, mixed, and indeterminate subtypes according to the Laurén classification. Numerous studies have demonstrated how the interaction of dietary and lifestyle factors, host genetic factors, epigenetic changes and genetic changes, and Helicobacter pylori infection contributes to the development of gastric cancer. Recently, a comprehensive study by The Cancer Genome Atlas (TCGA) consortium revealed four molecular subtypes of gastric cancer, including chromosomal instability (CIN), microsatellite instability-high (MSI), genomically stable (GS), and Epstein–Barr virus (EBV) molecular subtypes. Although the relationship between Helicobacter pylori infection and development of gastric cancer has been explored in past decades, uncovering the molecular mechanisms by Helicobacter pylori that contribute to gastric carcinogenesis is still warranted. Furthermore, the great efforts in clarifying the origin of four subtypes of gastric cancer, CIN, MSI, GS, and EBV, will help us to prevent and treat gastric cancer. In this Special Issue, we welcome submissions that cover all features associated with molecular mechanisms of gastric cancer development, both in the form of reviews and original papers. This Special Issue is aimed at summarizing the molecular mechanisms of development across major molecular subtypes of gastric cancer and the prospects for prevention of gastric cancer development.

Prof. Sung-Hsin Kuo
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • Gastric cancer
  • Helicobacter pylori
  • Molecular mechanism
  • Carcinogenesis
  • Cancer development
  • Epstein–Barr virus
  • Chromosomal instability
  • Microsatellite instability
  • Genomic changes

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Published Papers (3 papers)

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Research

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18 pages, 4437 KiB  
Article
Consensus Molecular Subtypes Efficiently Classify Gastric Adenocarcinomas and Predict the Response to Anti-PD-1 Immunotherapy
by Xiangyan Wu, Yuhan Ye, Kenneth J. Vega and Jiannan Yao
Cancers 2022, 14(15), 3740; https://doi.org/10.3390/cancers14153740 - 31 Jul 2022
Cited by 2 | Viewed by 3152
Abstract
Background: Gastric adenocarcinoma (GAC) is highly heterogeneous and closely related to colorectal cancer (CRC) both molecularly and functionally. GAC is currently subtyped using a system developed by TCGA. However, with the emergence of immunotherapies, this system has failed to identify suitable treatment candidates. [...] Read more.
Background: Gastric adenocarcinoma (GAC) is highly heterogeneous and closely related to colorectal cancer (CRC) both molecularly and functionally. GAC is currently subtyped using a system developed by TCGA. However, with the emergence of immunotherapies, this system has failed to identify suitable treatment candidates. Methods: Consensus molecular subtypes (CMSs) developed for CRC were used for molecular subtyping in GAC based on public expression cohorts, including TCGA, ACRG, and a cohort of GAC patients treated with the programmed cell death 1 (PD-1) inhibitor pembrolizumab. All aspects of each subtype, including clinical outcome, molecular characteristics, oncogenic pathway activity, and the response to immunotherapy, were fully explored. Results: CMS classification was efficiently applied to GAC. CMS4, characterized by EMT activation, stromal invasion, angiogenesis, and the worst clinical outcomes (median OS 24.2 months), was the predominant subtype (38.8%~44.3%) and an independent prognostic indicator that outperformed classical TCGA subtyping. CMS1 (20.9%~21.5%) displayed hypermutation, low SCNV, immune activation, and best clinical outcomes (median OS > 120 months). CMS3 (17.95%~25.7%) was characterized by overactive metabolism, KRAS mutation, and intermediate outcomes (median OS 85.6 months). CMS2 (14.6%~16.3%) was enriched for WNT and MYC activation, differentiated epithelial characteristics, APC mutation, lack of ARID1A, and intermediate outcomes (median OS 48.7 months). Notably, CMS1 was strongly correlated with immunotherapy biomarkers and favorable for the anti-PD-1 drug pembrolizumab, whereas CMS4 was poorly responsive but became more sensitive after EMT-based stratification. Conclusions: Our study reveals the practical utility of CMS classification for GAC to improve clinical outcomes and identify candidates who will respond to immunotherapy. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Gastric Cancer Development)
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14 pages, 1332 KiB  
Article
Impact of Tumor Localization and Molecular Subtypes on the Prognostic and Predictive Significance of p53 Expression in Gastric Cancer
by Bianca Grosser, Meike Kohlruss, Julia Slotta-Huspenina, Moritz Jesinghaus, Nicole Pfarr, Katja Steiger, Alexander Novotny, Matthias M. Gaida, Thomas Schmidt, Alexander Hapfelmeier, Katja Ott, Wilko Weichert and Gisela Keller
Cancers 2020, 12(6), 1689; https://doi.org/10.3390/cancers12061689 - 25 Jun 2020
Cited by 14 | Viewed by 3001
Abstract
We investigated the prognostic and predictive impact of p53 expression for gastric cancer (GC) patients treated without or with preoperative chemotherapy (CTx) and its relationship with specific molecular GC subtypes. Specimens from 694 GC patients (562 surgical resection specimens without or after CTx, [...] Read more.
We investigated the prognostic and predictive impact of p53 expression for gastric cancer (GC) patients treated without or with preoperative chemotherapy (CTx) and its relationship with specific molecular GC subtypes. Specimens from 694 GC patients (562 surgical resection specimens without or after CTx, 132 biopsies before CTx) were analyzed by p53 immunohistochemistry. High (H) and low (L) microsatellite instability (MSI) and Epstein–Barr virus positivity were determined previously. Our results show that aberrant p53 expression was a negative prognostic factor in uni- and multivariable analysis in the resection specimens cohort (each p < 0.01). Subgroup analysis showed the strongest prognostic effect for patients with distally located tumors or no CTx treatment. In the biopsy cohort before CTx, p53 did not predict response or survival. p53 expression was significantly different among the molecular subtypes in surgical resection and bioptic specimens with strong association of altered p53 with MSI-L. Patients with MSI-H and aberrant p53 showed the worst survival in the biopsy cohort. In conclusion, the prognostic impact of p53 in GC differs according to tumor localization and CTx. Altered p53 is characteristic for MSI-L, and the p53 status in biopsies before CTx delineates MSI-H subtypes with inverse prognostic impact. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Gastric Cancer Development)
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Review

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11 pages, 1815 KiB  
Review
Gastric Cancer Staging: Is It Time for Magnetic Resonance Imaging?
by Matteo Renzulli, Alfredo Clemente, Daniele Spinelli, Anna Maria Ierardi, Giovanni Marasco, Davide Farina, Stefano Brocchi, Matteo Ravaioli, Irene Pettinari, Matteo Cescon, Alfonso Reginelli, Salvatore Cappabianca, Gianpaolo Carrafiello and Rita Golfieri
Cancers 2020, 12(6), 1402; https://doi.org/10.3390/cancers12061402 - 29 May 2020
Cited by 26 | Viewed by 3751
Abstract
Gastric cancer (GC) is a common cancer worldwide. Its incidence and mortality vary depending on geographic area, with the highest rates in Asian countries, particularly in China, Japan, and South Korea. Accurate imaging staging has become crucial for the application of various treatment [...] Read more.
Gastric cancer (GC) is a common cancer worldwide. Its incidence and mortality vary depending on geographic area, with the highest rates in Asian countries, particularly in China, Japan, and South Korea. Accurate imaging staging has become crucial for the application of various treatment strategies, especially for curative treatments in early stages. Unfortunately, most GCs are still diagnosed at an advanced stage, with the peritoneum (61–80%), distant lymph nodes (44–50%), and liver (26–38%) as the most common metastatic locations. Metastatic disease is limited to the peritoneum in 58% of cases; in nonperitoneal distant metastases, the most involved GC metastasization site is the liver (82%). The eighth edition of the tumor-node-metastasis staging system is the most commonly used system for determining GC prognosis. Endoscopic ultrasonography, computed tomography, and 18-fluorideoxyglucose positron emission tomography are historically the most accurate imaging techniques for GC staging. However, studies have recently shown renewed interest in magnetic resonance imaging (MRI) as a useful tool in GC staging, especially for distant metastasis assessment. The technical improvement of diffusion-weighted imaging and the increasing use of hepatobiliary contrast agents have been shown to increase the diagnostic performance of MRI, particularly for detecting peritoneal and liver metastasis. However, no principal oncological guidelines have included the use of MRI as a first-line technique for distant metastasis evaluation during the GC staging process, such as the National Comprehensive Cancer Network Guidelines. This review analyzed the role of the principal imaging techniques in GC diagnosis and staging, focusing on the potential role of MRI, especially for assessing peritoneal and liver metastases. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Gastric Cancer Development)
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