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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inorganic pyrophosphatase (PPase) catalyzes the hydrolysis of pyrophosphate to form orthophosphate. Pyrophosphate can substitute for ATP under certain circumstances. We previously conducted a proteomic analysis to investigate tumor-specific protein expression in gastric cancer, and PPase was identified as a potential gastric tumor-specific marker; it was therefore selected for further study. Clinicopathological analysis, using proteomic analysis and immunohistochemistry, was used to validate PPase as a prognostic marker in gastric cancers. Proteomic analysis showed that PPase was overexpressed in patients with lymph node (LN) metastases and high tumor node metastasis (TNM) stages (p < 0.05). Based on immunohistochemistry, patients whose tumors overexpressed PPase had higher T stages, LN metastasis, a higher TNM stage, a higher cancer recurrence rate, and shorter survival times than patients whose tumors exhibited PPase underexpression (p < 0.05). Gain-of-function and loss-of-function approaches were employed to examine the malignant phenotypes of PPase-overexpressing or PPase-depleted cells. A decrease in PPase expression caused a significant decrease in gastric cancer cell migration and invasion in vitro, whereas forced overexpression of PPase enhanced migration but not invasion. Our findings indicate that PPase is involved in gastric tumor progression and that PPase may be a useful marker for poor prognosis of human gastric cancers.
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PMID:Pyrophosphatase overexpression is associated with cell migration, invasion, and poor prognosis in gastric cancer. 2279 19

Tumorigenesis is a multistep process that attributes to the sequential accumulation of abnormal expression in key oncogenes or tumor suppressors. We aimed to identify stage-specific biomarkers to distinguish lung adenocarcinoma (LAC) stages in cancer progression. RNA-sequencing data of LAC and matched adjacent non-cancer tissues were downloaded from the Cancer Genome Atlas, including 29 pairs of samples from LAC at stage I, 14 from LAC at stage II, 13 from LAC at stage III, and 1 from LAC at stage IV. Differentially expressed genes (DEGs) were analyzed for each case at different stages of LAC. DEGs were further annotated based on transcription factor data information, tumor-associated gene database, and protein-protein interaction database. Functional annotation was performed for genes in PPI network by DAVID online tool. Our analysis identified 11 high-frequency DEGs in the stage I, 29 in the stage II, and 90 in the stage III of LAC. Among them, eight genes were significantly correlated with LAC stages and identified as biomarkers in LAC progression. ANGPTL5, C7orf16, EDN3, LOC150622, HOXA11AS, IL1F5, and USH1G significantly distinguished stage III from stages I and II. GJB6 was significantly enriched in the gap junction trafficking pathway, while C7orf16 and EDN3 were enriched in Wnt signaling pathway, cell cycle, and G protein-coupled receptor (GPCR) signaling. Up-regulated GJB6 especially in LAC stage II and down-regulated C7orf16 and EDN3 specifically in stage III were identified as biomarkers for distinguishing cancer stage in tumor progression through dysregulating gap junction, Wnt signaling, and GPCR signaling pathways.
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PMID:Identification of stage-specific biomarkers in lung adenocarcinoma based on RNA-seq data. 2586 Oct 20

Cancer forms a robust system capable of maintaining stable functioning (cell sustenance and proliferation) despite perturbations. Cancer progresses as stages over time typically with increasing aggressiveness and worsening prognosis. Characterizing these stages and identifying the genes driving transitions between them is critical to understand cancer progression and to develop effective anti-cancer therapies. In this work, we propose a novel model for the `cancer system' as a Boolean state space in which a Boolean network, built from protein-interaction and gene-expression data from different stages of cancer, transits between Boolean satisfiability states by "editing" interactions and "flipping" genes. Edits reflect rewiring of the PPI network while flipping of genes reflect activation or silencing of genes between stages. We formulate a minimization problem min flip to identify these genes driving the transitions. The application of our model (called BoolSpace) on three case studies-pancreatic and breast tumours in human and post spinal-cord injury (SCI) in rats-reveals valuable insights into the phenomenon of cancer progression: (i) interactions involved in core cell-cycle and DNA-damage repair pathways are significantly rewired in tumours, indicating significant impact to key genome-stabilizing mechanisms; (ii) several of the genes flipped are serine/threonine kinases which act as biological switches, reflecting cellular switching mechanisms between stages; and (iii) different sets of genes are flipped during the initial and final stages indicating a pattern to tumour progression. Based on these results, we hypothesize that robustness of cancer partly stems from "passing of the baton" between genes at different stages-genes from different biological processes and/or cellular components are involved in different stages of tumour progression thereby allowing tumour cells to evade targeted therapy, and therefore an effective therapy should target a "cover set" of these genes. A C/C++ implementation of BoolSpace is freely available at: http://www.bioinformatics.org.au/tools-data.
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PMID:Evolution and Controllability of Cancer Networks: A Boolean Perspective. 2635 10

The most important novel findings presented on oesophageal disease in DDW 2015 were the following: 1) GERD: a) hypervigilance seems to be a key pathogenic factor in reflux symptoms refractory to PPI; b) post-reflux swallowing-induced peristaltic waves could be an excellent diagnostic criterion for GERD; c) laryngeal pH-metry is not useful in the diagnosis of extra-oesophageal symptoms; d) the recommendation of weight loss adequately recorded in the clinical reports of patients with GERD and obesity or overweight is an excellent quality indicator and is associated with better outcomes. 2) Barrett's oesophagus: a) persistent low-grade dysplasia in more than one endoscopy and a diagnosis of "indefinite for dysplasia" are associated with a high risk of neoplastic progression; b) narrow-band imaging allows areas of dysplasia on Barrett's oesophagus to be identified with high sensitivity and specificity; c) initial endoscopy fails to identify a high percentage of advanced neoplasms in Barrett's oesophagus. Early re-endoscopy should be considered; d) endoscopists specialized in Barret's oesophagus obtain a much higher yield in the diagnosis of advanced lesions. Patients at high risk-men, older patients, smokers and those with long-segment Barrett's oesophagus-could benefit from follow-up in a referral center. 3) Achalasia: POEM seems safe and effective, independently from patient characteristics (age, comorbidity) and the technical variations used. 4) Eosinophilic esophagitis: topical budesonide and exclusion diets are reasonably effective in PPI non-responders.
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PMID:[Oesophageal diseases: gastroesophageal reflux disease, Barrett's disease, achalasia and eosinophilic oesophagitis]. 2652 Jan 96

Barrett's esophagus is common in Western countries, but progression to esophageal adenocarcinoma is uncommon. Chemoprevention therefore needs to consider whether benefits outweigh risks given an otherwise healthy population. This will depend on the particular population at risk and the relative safety of a potential preventive agent. Most evidence regarding the potential benefit of chemoprevention of Barrett's esophagus and prevention of progression to esophageal adenocarcinoma is based on observational studies such as case-control and cohort studies. Given the potential benefits and relatively low risks, patients with BE should receive once-daily PPI therapy, but routine use of twice-daily PPI is not recommended unless necessitated by poor control of reflux symptoms or esophagitis. Recent data suggest that the inverse associations between aspirin/NSAID use and esophageal adenocarcinoma may be the result of reducing neoplastic progression (from metaplasia to dysplasia and carcinoma) rather than initiation of Barrett's esophagus. While substantial associative data suggest a potential benefit of aspirin and nonaspirin NSAIDs in reducing the risk of progression of Barrett's esophagus, the low risk of progression and the potential risks (gastrointestinal bleeding, complicated ulcer disease, hemorrhagic stroke) do not warrant routine use, unless dictated by cardiovascular risk. Chemoprevention after mucosal ablation in those at highest risk of post-ablation recurrence (dysplastic Barrett's) is currently under investigation.
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PMID:Chemoprevention of Barrett's Esophagus and Esophageal Adenocarcinoma. 2994 66

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide. More than 90% of primary HCC is HCC. Hepatitis C virus (HCV) infection and alcohol consumption have been widely accepted as two major risk factors for developing HCC. Herein, we aimed to identify DNA methylation genes related to both HCV infection and alcohol consumption. In this study, we identified methylation genes that were associated with the risk of HCV infection and alcohol consumption, respectively, by a large-scale bioinformatic analysis. Through PPI network analysis, we revealed the associations between the two types of genes and found six hub genes-TAF1, SAT1, Phospholipase C-beta 2, FGD1, ARHGAP4, and ARHGEF9-that may be associated with both HCV infection and alcohol consumption. Gene Ontology enrichment analysis was used to analyze the function which these genes in the network enriched. Among them, TAF1, SAT1, and ARHGEF9 were methylated genes that have been found to be related to tumor progression in HCC patients. Through independent data sets, we verified the methylation pattern of these six genes in HCC samples that had both HCV infection and alcohol consumption risks. Furthermore, we found that three of the six methylated genes were also associated with the prognosis of HCC patients. To summarize, we identified six hub genes that were associated with both HCV infection and alcohol consumption in the progress of HCC. The six methylation genes that might play an important role in both HCV infection and alcohol consumption would be potential therapy targets for HCC.
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PMID:Identification of TAF1, SAT1, and ARHGEF9 as DNA methylation biomarkers for hepatocellular carcinoma. 3128 7

Glioblastoma (GBM) is one of the most common malignancies of the central nervous system, and the Isocitrate Dehydrogenase (IDH) mutation status of GBM has been recognized as a critical prognostic indicator. However, the molecular mechanism underlying the GBM with different IDH mutation status is still not unclear. In this study, a total of 353 DEGs including 207 up-regulated and 146 down-regulated were screened from multiple GBM data sets. Moreover, the biological processes and pathways enriched by DEGs were mainly associated with tumor progression, especially invasion and migration. Then, eight hub genes, including SDC4, SERPINE1, TNC, THBS1, COL1A1, CXCL8, TIMP1 and VEGFA, were selected from a PPI network. Finally, core genes, SERPINE1 and TIMP1, were identified from hub genes by survival analysis and sample validation. Overall, in this study, we revealed underlying molecular mechanisms in GBMs with different IDH mutation status and identified core genes that could be potential markers and targets for diagnosis and treatment of GBMs.
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PMID:Identification of two core genes in glioblastomas with different isocitrate dehydrogenase mutation status. 3291 3

The AR signaling pathway plays an important role in initiation and progression of many hormone-related cancers including prostate, bladder, kidney, lung, and breast cancer. However, the potential roles of androgen-responsive long noncoding RNAs (lncRNAs) in hormone-related cancers remained unclear. In the present study, we identified 469 novel androgen-responsive lncRNAs using microarray data. After validating the accuracy of the array data, we constructed a transcriptional network which contained more than 30 transcriptional factors using ChIP-seq data to explore upstream regulators of androgen-responsive lncRNAs. Next, we conducted bioinformatics analysis to identify lncRNA-miRNA-mRNA regulatory network. To explore the potential roles of androgen-responsive lncRNAs in hormone-related cancers, we performed coexpression network and PPI network analyses using TCGA data. GO and KEGG analyses showed these lncRNAs were mainly involved in regulating signal transduction, transcription, development, cell adhesion, immune response, cell differentiation, and MAPK signaling pathway. We also highlight the prognostic value of HPN-AS1, TPTEP1, and LINC00623 in cancer outcomes. Our results suggest that androgen-responsive lncRNAs played important roles in regulating hormone-related cancer progression and could be novel molecular biomarkers.
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PMID:Comprehensive Characterization of Androgen-Responsive lncRNAs Mediated Regulatory Network in Hormone-Related Cancers. 3308 88

CircRNAs are now under hot discussion as novel promising bio-markers for patients with clear cell renal cell carcinoma. The purpose of our study is to identify several circRNAs related to the metastasis and progression of clear cell renal cell carcinoma, and to further investigate the mechanism of their influence on tumor progression. The transcriptome data of ccRCC and clinical characteristics used in this study were downloaded from the The Cancer Genome Atlas and Gene Expression Omnibus database. A total of 114 circRNAs were found to be related to tumor initiation, progression and metastasis after the intersection. In addition, 14 miRNAs and 201 eligible mRNAs were selected as targets gene, respectively. CeRNA network was constructed based on 8 circRNAs, 14 miRNAs, and 201 mRNAs. Besides, another 6 hub genes were identified via the PPI network. It should be noted that only TRIM2 was confirmed as an independent prognostic factor, which was simultaneously significantly related to both clinical stage and pathological grade in clinical cohorts. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis indicated the possible function of TRIM2 in ccRCC progression, such as ubiquitin mediated protein hydrolysis, cell adhesion molecules, Th17 cell differentiation signaling pathway and so on. Gene set enrichment analysis analysis revealed that TRIM2 may be involved in ubiquitin mediated proteolysis, apoptosis, autophagy and citrate cycle TCA cycle. Hub circ_RNAs expressions were validated in ccRCC tissues and cell lines. Our study revealed that the hsa_circ_0002286 / has-mir-222-5p / TRIM2 axis played a critical role in the progression of ccRCC. Specifically, it may inhibit the metastasis and progression of ccRCC, which could serve as a potential therapeutic target.
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PMID:Construction of circRNA-based ceRNA network to reveal the role of circRNAs in the progression and prognosis of metastatic clear cell renal cell carcinoma. 3322 11