Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

HER2 aberrations and heterogeneity in cancers of the digestive system: Implications for pathologists and gastroenterologists.

ABSTRACT: Management of cancers of the digestive system has progressed rapidly into the molecular era. Despite the significant recent achievements in the diagnosis and treatment of these patients, the number of deaths for these tumors has currently plateaued. Many investigations have assessed the role of HER2 in tumors of the digestive system in both prognostic and therapeutic settings, with heterogeneous results. Novel testing and treatment guidelines are emerging, in particular in gastric and colorectal cancers. However, further advances are needed. In this review we provide a comprehensive overview of the current state-of-knowledge of HER2 alterations in the most common tumors of the digestive system and discuss the operational implications of HER2 testing.

SUBMITTER: Fusco N

PROVIDER: S-EPMC5028807 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

HER2 aberrations and heterogeneity in cancers of the digestive system: Implications for pathologists and gastroenterologists.

Fusco Nicola N Bosari Silvano S

World journal of gastroenterology 20160901 35

Management of cancers of the digestive system has progressed rapidly into the molecular era. Despite the significant recent achievements in the diagnosis and treatment of these patients, the number of deaths for these tumors has currently plateaued. Many investigations have assessed the role of HER2 in tumors of the digestive system in both prognostic and therapeutic settings, with heterogeneous results. Novel testing and treatment guidelines are emerging, in particular in gastric and colorectal ...[more]

PMID: 27672288

Similar Datasets

Gallstones, cholecystectomy, and risk of digestive system cancers.

Project description:Gallstones and cholecystectomy may be related to digestive system cancer through inflammation, altered bile flux, and changes in metabolic hormone levels. Although gallstones are recognized causes of gallbladder cancer, associations with other cancers of the digestive system are poorly established. We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database (1992-2005), which includes 17 cancer registries that cover approximately 26% of the US population, to identify first primary cancers (n = 236,850) occurring in persons aged ≥66 years and 100,000 cancer-free population-based controls frequency-matched by calendar year, age, and gender. Odds ratios and 95% confidence intervals were calculated using logistic regression analysis, adjusting for the matching factors. Gallstones and cholecystectomy were associated with increased risk of noncardia gastric cancer (odds ratio (OR) = 1.21 (95% confidence interval (CI): 1.11, 1.32) and OR = 1.26 (95% CI: 1.13, 1.40), respectively), small-intestine carcinoid (OR = 1.27 (95% CI: 1.01, 1.60) and OR = 1.78 (95% CI: 1.41, 2.25)), liver cancer (OR = 2.35 (95% CI: 2.18, 2.54) and OR = 1.26 (95% CI: 1.12, 1.41)), and pancreatic cancer (OR = 1.24 (95% CI: 1.16, 1.31) and OR = 1.23 (95% CI: 1.15, 1.33)). Colorectal cancer risk associated with gallstones and cholecystectomy decreased with increasing distance from the common bile duct (P-trend < 0.001). Hence, gallstones and cholecystectomy are associated with the risk of cancers occurring throughout the digestive tract.

| S-EPMC5856086 | biostudies-literature

Prognostic implications of HER2 heterogeneity in gastric cancer.

Project description:The prognostic implications of human epidermal growth receptor 2 (HER2) heterogeneity in gastric cancer (GC) are not well established. Therefore, the aim of the present study was to determine to the effect of HER2 status on the prognosis of GC patients. We retrieved data on 248 pathologically-confirmed, consecutive patients with primary adenocarcinoma of the stomach or gastro-esophageal junction who underwent surgical resection at Kurume University Medical Center between July 2000 and December 2012. HER2 status was classified as HER2 positive or negative and HER2 heterogeneity or homogeneity. The endpoint was overall survival (OS), which was compared using the generalized Wilcoxon test. HER2 status was positive in 36 patients (14.5%) and negative in 212 patients (85.5%). Among the 36 HER2 positive patients, 25 patients (69.4%) had HER2 heterogeneity and the remaining 11 patients (30.6%) had HER2 homogeneity. Among the 141 patients with stage III or IV disease, the prognosis of the HER2 homogeneity group was significantly worse than that of the HER2 heterogeneity group (p = 0.019; median OS 193 and 831 days, respectively). The prognosis was not significantly different between the HER2 positive group and the HER2 negative group (p = 0.84; median OS 552 and 556 days, respectively). The present study was conducted with small samples, however, the results of the study suggest that HER2 homogeneity but not HER2 positivity may represent a prognostic indicator in GC.

| S-EPMC5823644 | biostudies-literature

Circulating vitamin C and digestive system cancers: Mendelian randomization study.

Project description:Background & aimsVitamin C is an antioxidant with a potential role in the prevention of digestive system cancers, but there is yet no consensus whether vitamin C has a causal role in these cancers. The aim of this study was to utilize Mendelian randomization to decipher the potential causal associations of vitamin C with risk of digestive system cancers.MethodsTen genetic variants previously found to be significantly associated with circulating vitamin C were used as instrumental variables. Effect size estimates for the genetic associations of the vitamin C-associated genetic variants with six major malignancies of digestive system were obtained from the FinnGen (N = 309 154) and UK Biobank (N = 367 542) studies. Results from the two studies were combined using meta-analysis.ResultsGenetically predicted higher circulating vitamin C showed a suggestive association with lower risk of small intestine and colorectal cancer after accounting for multiple testing. The odds ratio per 1 standard deviation increment in circulating vitamin C was 0.55 (95% confidence interval 0.32-0.94; P = 0.029) for small intestine cancer and 0.84 (95% confidence interval 0.73-0.96; P = 0.013) for colorectal cancer. There was a suggestive association between genetically predicted higher circulating vitamin C with lower risk of liver cancer in FinnGen but no association in the meta-analysis (odds ratio 0.69; 95% CI 0.36-1.32; P = 0.265). Genetically predicted circulating vitamin C was not associated with cancers of the esophagus, stomach, or pancreas.ConclusionThis Mendelian randomization study indicates that vitamin C might play a role in the prevention of small intestine and colorectal cancer.

| S-EPMC7613472 | biostudies-literature

Predictive role of XRCC5/XRCC6 genotypes in digestive system cancers.

Project description:Cancers are a worldwide concern; oral, esophageal and gastrointestinal cancers represent important causes of cancer-related mortality and contribute to a significant burden of human health. The DNA repair systems are the genome caretakers, playing a critical role in the initiation and progression of cancers. However, the association between the genomic variations of DNA repair genes and cancer susceptibility is not well understood. This review focuses on the polymorphic genotypes of the non-homologous end-joining DNA repair system, highlighting the role of two genes of this pathway, XRCC5 and XRCC6, in the susceptibility to digestive system cancers and discussing their potential contributions to personalized medicine.

| S-EPMC3251741 | biostudies-literature

The Regulatory Functions of Circular RNAs in Digestive System Cancers.

Project description:Circular ribonucleic acids (circRNAs), which are a type of covalently closed circular RNA, are receiving increasing attention. An increasing amount of evidence suggests that circRNAs are involved in the biogenesis and development of multiple diseases such as digestive system cancers. Dysregulated circRNAs have been found to act as oncogenes or tumour suppressors in digestive system cancers. Moreover, circRNAs are related to ageing and a wide variety of processes in tumour cells, such as cell apoptosis, invasion, migration, and proliferation. Moreover, circRNAs can perform a remarkable multitude of biological functions, such as regulating splicing or transcription, binding RNA-binding proteins to enable function, acting as microRNA (miRNA) sponges, and undergoing translated into proteins. However, in digestive system cancers, circRNAs function mainly as miRNA sponges. Herein, we summarise the latest research progress on biological functions of circRNAs in digestive system cancers. This review serves as a synopsis of potential therapeutic targets and biological markers for digestive system cancer.

| S-EPMC7140005 | biostudies-literature

Suicide rates among patients with cancers of the digestive system.

Project description:ObjectivePrevious studies have suggested that suicide rates are elevated among cancer patients relative to the general population. In this analysis, we comprehensively evaluated characteristics associated with higher suicide rates among patients with cancers of the digestive system.MethodsUsing the United States Surveillance, Epidemiology, and End Results database, we identified all patients diagnosed with digestive system cancers during 2000 to 2014. Patients were classified as having died of suicide if their cause of death in Surveillance, Epidemiology, and End Results was listed as "suicide and self-inflicted injury." Suicide rates were compared to age-, sex-, and race-adjusted rates in the general population.ResultsA total of 881 suicides were identified among 856 293 patients diagnosed with digestive system cancers. The suicide rate in this population was 32.8 per 100 000 person-years and was nearly twice that in the general population (standardized mortality ratio [SMR] = 1.91; 95% CI, 1.79-2.04). Suicide rates were significantly elevated for all cancer sites but were highest for esophageal (SMR = 5.03), pancreatic (SMR = 5.28), stomach (SMR = 2.84), and liver (SMR = 2.14) cancers. Standardized mortality ratios for suicide were highest within the first 5 years of diagnosis and increased with age at diagnosis for all sites except colon and stomach.ConclusionsPatients with cancers of the digestive system have a higher incidence of suicide than the general population. Suicide rates among esophageal and pancreatic cancer patients are more than 5 times general population rates. The involvement of psychiatrists and other mental health professionals may be a critical component of cancer care for these high-risk patient subgroups.

| S-EPMC6584762 | biostudies-literature

Biological and clinical implications of FGFR aberrations in paediatric and young adult cancers.

Project description:Rare but recurrent mutations in the fibroblast growth factor receptor (FGFR) pathways, most commonly in one of the four FGFR receptor tyrosine kinase genes, can potentially be targeted with broad-spectrum multi-kinase or FGFR selective inhibitors. The complete spectrum of these mutations in paediatric cancers is emerging as precision medicine programs perform comprehensive sequencing of individual tumours. Identification of patients most likely to benefit from FGFR inhibition currently rests on identifying activating FGFR mutations, gene fusions, or gene amplification events. However, the expanding use of transcriptome sequencing (RNAseq) has identified that many tumours overexpress FGFRs, in the absence of any genomic aberration. The challenge now presented is to determine when this indicates true FGFR oncogenic activity. Under-appreciated mechanisms of FGFR pathway activation, including alternate FGFR transcript expression and concomitant FGFR and FGF ligand expression, may mark those tumours where FGFR overexpression is indicative of a dependence on FGFR signalling. In this review, we provide a comprehensive and mechanistic overview of FGFR pathway aberrations and their functional consequences in paediatric cancer. We explore how FGFR over expression might be associated with true receptor activation. Further, we discuss the therapeutic implications of these aberrations in the paediatric setting and outline current and emerging therapeutic strategies to treat paediatric patients with FGFR-driven cancers.

| S-EPMC10244177 | biostudies-literature

The role of hypoxia-inducible factor-2 in digestive system cancers.

Project description:Hypoxia is an all but ubiquitous phenomenon in cancers. Two known hypoxia-inducible factors (HIFs), HIF-1α and HIF-2α, primarily mediate the transcriptional response to hypoxia. Despite the high homology between HIF-1α and HIF-2α, emerging evidence suggests differences between both molecules in terms of transcriptional targets as well as impact on multiple physiological pathways and tumorigenesis. To date, much progress has been made toward understanding the roles of HIF-2α in digestive system cancers. Indeed, HIF-2α has been shown to regulate multiple aspects of digestive system cancers, including cell proliferation, angiogenesis and apoptosis, metabolism, metastasis and resistance to chemotherapy. These findings make HIF-2α a critical regulator of this malignant phenotype. Here we summarize the function of HIF-2 during cancer development as well as its contribution to tumorigenesis in digestive system malignancies.

| S-EPMC4669763 | biostudies-other

Genetically predicted circulating B vitamins in relation to digestive system cancers.

Project description:BackgroundFolate, vitamin B6 and vitamin B12 have been associated with digestive system cancers. We conducted a two-sample Mendelian randomisation study to assess the causality of these associations.MethodsTwo, one and 14 independent single nucleotide polymorphisms associated with serum folate, vitamin B6 and vitamin B12 at the genome-wide significance threshold were selected as genetic instruments. Summary-level data for the associations of the vitamin-associated genetic variants with cancer were obtained from the UK Biobank study including 367,561 individuals and FinnGen consortium comprising up to 176,899 participants.ResultsGenetically predicted folate and vitamin B6 concentrations were not associated with overall cancer, overall digestive system cancer or oesophageal, gastric, colorectal or pancreatic cancer. Genetically predicted vitamin B12 concentrations were positively associated with overall digestive system cancer (ORSD, 1.12; 95% CI 1.04, 1.21, p = 0.003) and colorectal cancer (ORSD 1.16; 95% CI 1.06, 1.26, p = 0.001) in UK Biobank. Results for colorectal cancer were consistent in FinnGen and the combined ORSD was 1.16 (95% CI 1.08, 1.25, p < 0.001). There was no association of genetically predicted vitamin B12 with any other site-specific digestive system cancers or overall cancer.ConclusionsThese results provide evidence to suggest that elevated serum vitamin B12 concentrations are associated with colorectal cancer.

| S-EPMC8184856 | biostudies-literature

Diagnostic and Prognostic Roles of Thrombospondin-2 in Digestive System Cancers.

Project description:BackgroundCancers of digestive system have high case-fatality rate. It is important to find more appropriate methods in diagnosing and predicting gastrointestinal malignances. And thrombospondin-2 (TSP-2) was reported to have the functions, although results were not identical. So we performed this meta-analysis to clarify the significance of TSP-2 in this area.MethodsPubMed, Embase, Web of Science, Cochrane Library, and Clinicaltrial.gov were searched for relevant studies. Data were extracted from these involved records. For the meta-analysis of diagnostic test, bivariate mixed effect model was used to estimate diagnostic accuracy. For prognosis part, HRs and their 95% CIs were pooled to compare the overall survival (OS) and disease-free survival (DFS) between patients with high TSP-2 and low TSP-2.ResultsNine records were eligible for the analysis of diagnostic test. Pooled results were as follows: sensitivity 0.60 (0.52, 0.68), specificity 0.96 (0.91, 0.98), positive likelihood ratio (PLR) 15.4 (7.3, 32.2), negative likelihood ratio (NLR) 0.42 (0.34, 0.50), and diagnostic odds ratio (DOR) 37 (18, 76). While in prognosis part, 10 articles were included. Patients with increased TSP-2 had shorter OS (HR = 1.64, 95% CI = 1.21-2.22); however, no difference was found in DFS between TSP-2 high and low groups (HR = 1.44, 95% CI = 0.28-7.33).ConclusionsTSP-2, as a diagnostic marker, has a high specificity but a moderate sensitivity. Meanwhile, it plays a role in predicting OS. Therefore, making TSP-2 a routine assay could be beneficial to high-risk individuals and patients with digestive malignances.

| S-EPMC9303135 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data