Gastric Cancer: Epidemiology, Risk Factors, Classification, Genomic Characteristics and Treatment Strategies

Machlowska, Julita; Baj, Jacek; Sitarz, Monika; Maciejewski, Ryszard; Sitarz, Robert

doi:10.3390/ijms21114012

Cited by 909 publications

(753 citation statements)

References 154 publications

(152 reference statements)

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“…Moreover, approximately 10% of GC is detected in those younger than 45 years old, a trend that is increasing [13]. However, as for early-onset SRCC, some have reported a knowledge gap [14,15].…”

Section: Discussionmentioning

confidence: 99%

Comparison of metastasis between early-onset and late-onset gastric signet ring cell carcinoma

Zhou¹,

Ge²,

Liu³

2020

BMC Gastroenterol

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Background There is little knowledge to date about the distant metastasis of early-onset gastric signet ring cell carcinoma (SRCC) or the difference in metastasis based on age. Therefore, we conducted a comprehensive retrospective study using the Surveillance, Epidemiology, and End Results (SEER) database and data from our hospital. Methods Patients were collected from the SEER database and our hospital. Univariate and multivariate logistic regression analyses and propensity score matching (PSM) were used to identify risk factors for metastasis. K-M survival curves were generated to analyse patient survival. Results In total, we retrieved 2052 EOGC patients diagnosed with SRCC from the SEER database and included 403 patients from our hospital. K-M survival curves showed that late-onset SRCC patients had worse survival than early-onset patients but that late-onset SRCC patients were less likely to have distant metastasis, as validated by SEER data (OR = 0.462, 95%CI, 0.272–0.787; P = 0.004) and our data (OR = 0.301, 95%CI, 0.135–0.672; P = 0.003). Multivariate logistic regression and PSM analysis revealed that age of 45 or younger was an independent risk factor for distant metastasis. Conclusion Our study showed that distant metastasis was more common in early-onset SRCC than in late-onset SRCC. However, further studies are needed to explore the potential aetiologic basis for this disparity.

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Section: Discussionmentioning

confidence: 99%

Comparison of metastasis between early-onset and late-onset gastric signet ring cell carcinoma

Zhou¹,

Ge²,

Liu³

2020

BMC Gastroenterol

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“…It is estimated that the mortality of GC reaches 70% and is obviously higher than other epidemic diseases (28). With the improvement of standards of hygiene and the eradication of H. pylori, the incidence rate of GC has shown a decline trend and changed from the fourth most common cancer to the fth (29,30). However, the mortality rate of GC has not been signi cantly decreased.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis and Identification of Potential Biomarkers in Gastric Cancer

Yang¹,

Peng²,

Qin³

et al. 2020

Preprint

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Background: Although the morbidity and mortality of gastric cancer are declining, gastric cancer is still one of the most common causes of death. Early detection of gastric cancer is of great help to improve the survival rate, but the existing biomarkers are not sensitive to diagnose early gastric cancer. The aim of this study is to identify the novel biomarkers for gastric cancer.Methods: Three gene expression profiles (GSE27342, GSE63089, GSE33335) were downloaded from Gene Expression Omnibus database to select differentially expressed genes. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were performed to explore the biological functions of differentially expressed genes. Cytoscape was utilized to construct protein-protein interaction network and hub genes were analyzed by plugin cytoHubba of Cytoscape. Furthermore, Gene Expression Profiling Interactive Analysis and Kaplan-Meier plotter were used to verify the identified hub genes.Results: 35 overlapping differentially expressed genes were screened from gene expression datasets, which consisted of 11 up-regulated genes and 24 down-regulated genes. Gene Ontology functional enrichment analysis revealed that differentially expressed genes were significantly enriched in digestion, regulation of biological quality, response to hormone and steroid hormone, and homeostatic process. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed differentially expressed genes were enriched in the secretion of gastric acid and collecting duct acid, leukocyte transendothelial migration and ECM-receptor interaction. According to protein-protein interaction network, 10 hub genes were identified by Maximal Clique Centrality method.Conclusion: By using bioinformatics analysis, COL1A1, BGN, THY1, TFF2 and SST were identified as the potential biomarkers for early detection of gastric cancer.

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“…GC pathogenesis is closely related to the diet, environment, H. pylori infection, and genetic alterations [ 6 , 7 , 8 , 9 ]. The recognizable patterns of GC incorporate genetic alterations among various factors: cell cycle regulators, agents that regulate apoptosis, microsatellite instability, multidrug resistance proteins, factors that influence cell membrane properties, the module of HER2 expression, and agents with an impact on the progression of GC and peritoneal metastasis [ 10 , 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

High-Throughput Sequencing of Gastric Cancer Patients: Unravelling Genetic Predispositions Towards an Early-Onset Subtype

Machlowska

Kapusta

Baj

et al. 2020

Cancers

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Background: Gastric cancer is the fourth most common cause of cancer-related death. Currently, it is broadly accepted that the molecular complexity and heterogeneity of gastric cancer, both inter- and intra-tumor, display important barriers for finding specific biomarkers for the early detection and diagnosis of this malignancy. Early-onset gastric cancer is not as prevalent as conventional gastric carcinoma, but it is a preferable model for studying the genetic background, as young patients are less exposed to environmental factors, which influence cancer development. Aim: The main objective of this study was to reveal age-dependent genotypic characteristics of gastric cancer subtypes, as well as conduct mutation profiling for the most frequent alterations in gastric cancer development, using targeted next-generation sequencing technology. Patients and methods: The study group included 53 patients, consisting of 18 patients with conventional gastric cancer and 35 with an early-onset subtype. The DNA of all index cases was used for next-generation sequencing, employing a panel of 94 genes and 284 single nucleotide polymorphisms (SNPs) (TruSight Cancer Panel, Illumina), which is characteristic for common and rare types of cancer. Results: From among the 53 samples processed for sequencing, we were able to identify seven candidate genes (STK11, RET, FANCM, SLX4, WRN, MEN1, and KIT) and nine variants among them: one splice_acceptor, four synonymous, and four missense variants. These were selected for the age-dependent differentiation of gastric cancer subtypes. We found four variants with C-Score ≥ 10, as 10% of the most deleterious substitutions: rs1800862 (RET), rs10138997 (FANCM), rs2230009 (WRN), and rs2959656 (MEN1). We identified 36 different variants, among 24 different genes, which were the most frequent genetic alterations among study subjects. We found 16 different variants among the genes that were present in 100% of the total cohort: SDHB (rs2746462), ALK (rs1670283), XPC (rs2958057), RECQL4 (rs4925828; rs11342077, rs398010167; rs2721190), DDB2 (rs326212), MEN1 (rs540012), AIP (rs4930199), ATM (rs659243), HNF1A (rs1169305), BRCA2 (rs206075; rs169547), ERCC5 (rs9514066; rs9514067), and FANCI (rs7183618). Conclusions: The technology of next-generation sequencing is a useful tool for studying the development and progression of gastric carcinoma in a high-throughput way. Our study revealed that early-onset gastric cancer has a different mutation frequency profile in certain genes compared to conventional subtype.

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Gastric Cancer: Epidemiology, Risk Factors, Classification, Genomic Characteristics and Treatment Strategies

Cited by 909 publications

References 154 publications

Comparison of metastasis between early-onset and late-onset gastric signet ring cell carcinoma

Comparison of metastasis between early-onset and late-onset gastric signet ring cell carcinoma

Bioinformatics Analysis and Identification of Potential Biomarkers in Gastric Cancer

High-Throughput Sequencing of Gastric Cancer Patients: Unravelling Genetic Predispositions Towards an Early-Onset Subtype

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