Project description:Full title: Predictive Gene Signatures as Strong Prognostic Indicators of the Effectiveness of Bacillus Calmette–Guérin (BCG) Immunotherapy in Primary pT1 Bladder Cancers Intravesical BCG immunotherapy is effective in prevention of recurrence and progression in many cases of non-muscle invasive bladder cancer, but many patients fail to respond. This study identified predictive gene signatures in primary pT1 bladder cancer with BCG immunotherapy. Fourty-Eight patients with primary pT1 bladder cancer treated with BCG immunotherapy were used. Microarray gene expression analysis of the 48 primary bladder cancers was carried out. Predictive gene signatures were individually selected based on the recurrence and progression status. Among 43,148 unique genes, 424 and 287 candidate predictive genes that could predict recurrence and progression, respectively, were selected. Time to recurrence or progression was shorter for patients with poor-predictive gene signatures than good-predictive gene signatures (log-rank test, p <0.001, respectively). Validation of predictive gene signatures with RT-PCR was nearly identical to those of microarray (log-rank test, p <0.05, respectively). In multivariate regression analysis, predictive gene signatures were the only independent predictors of recurrence (HR 3.38, p = 0.048) or progression (HR 10.49, p = 0.048) in validation cohorts. Predictive gene signatures have strong diagnostic value for determining the response to intravesical BCG immunotherapy in primary pT1 bladder cancer. Keywords: Gene expression, Bladder cancer, BCG
Project description:Activating mutations in the KIT or PDGFRA receptor tyrosine kinases are hallmarks of gastrointestinal stromal tumor (GIST). The biological underpinnings of recurrence following resection or disease progression beyond kinase mutation are poorly understood. Utilizing chromatin immunoprecipitation with sequencing (ChIP-seq) of tumor samples and cell lines, we describe the enhancer landscape of GIST, highlighting genes that reinforce and extend our understanding of these neoplasms. A group of core transcription factors can be distinguished from others unique to localized and metastatic disease. The transcription factor HAND1 emerges in metastatic disease, binds to established GIST-associated enhancers and is required for GIST cell proliferation and KIT gene expression. The pattern of transcription factor expression in primary tumors is predictive of metastasis-free survival in GIST patients. These results provide insight into the enhancer landscape and transcription factor network underlying GIST, and define a new strategy for predicting clinical behavior of this disease.
Project description:Activating mutations in the KIT or PDGFRA receptor tyrosine kinases are hallmarks of gastrointestinal stromal tumor (GIST). The biological underpinnings of recurrence following resection or disease progression beyond kinase mutation are poorly understood. Utilizing chromatin immunoprecipitation with sequencing (ChIP-seq) of tumor samples and cell lines, we describe the enhancer landscape of GIST, highlighting genes that reinforce and extend our understanding of these neoplasms. A group of core transcription factors can be distinguished from others unique to localized and metastatic disease. The transcription factor HAND1 emerges in metastatic disease, binds to established GIST-associated enhancers and is required for GIST cell proliferation and KIT gene expression. The pattern of transcription factor expression in primary tumors is predictive of metastasis-free survival in GIST patients. These results provide insight into the enhancer landscape and transcription factor network underlying GIST, and define a new strategy for predicting clinical behavior of this disease.
Project description:Activating mutations in the KIT or PDGFRA receptor tyrosine kinases are hallmarks of gastrointestinal stromal tumor (GIST). The biological underpinnings of recurrence following resection or disease progression beyond kinase mutation are poorly understood. Utilizing chromatin immunoprecipitation with sequencing (ChIP-seq) of tumor samples and cell lines, we describe the enhancer landscape of GIST, highlighting genes that reinforce and extend our understanding of these neoplasms. A group of core transcription factors can be distinguished from others unique to localized and metastatic disease. The transcription factor HAND1 emerges in metastatic disease, binds to established GIST-associated enhancers and is required for GIST cell proliferation and KIT gene expression. The pattern of transcription factor expression in primary tumors is predictive of metastasis-free survival in GIST patients. These results provide insight into the enhancer landscape and transcription factor network underlying GIST, and define a new strategy for predicting clinical behavior of this disease.
Project description:Biomarkers play an important role in the detection and management of cancer patients. In gastrointestinal cancer, there is increasing interest in their development and validation according to specific tumor type. Prognostic biomarkers enable identification of patients with a more aggressive tumor evolution, while predictive biomarkers permit the identification of patients with a higher probability of responding or not to a specific treatment. Several biomarkers are currently widely employed in gastrointestinal cancers. These include rat sarcoma-2 virus (RAS) which is used to identify colorectal cancer (CRC) patients who will not respond to anti-epidermal growth factor receptor (EGFR) agents, while in gastric cancer, anti-human epidermal growth factor receptor 2 (HER2) therapy has been shown to only be active in HER2-positive patients. In pancreatic cancer, BRCA is a tool used to differentiate patients who are likely to respond to platinum-based combination therapies and to benefit from poly (ADP-ribose) polymerase (PARP) inhibitors. This review provides an update of the main biomarkers currently used in colorectal, gastric and pancreatic cancers, and reviews those that are being developed.
Project description:Interventions: Group 1: Determination of septin9 methylation status is done in all patientens preoperative. Those with positive methylation-status are assigned to arm 1.
Group 2: Determination of septin9 methylation status is done in all patientens preoperative. Those with negative methylation-status are assigned to arm 2.
Primary outcome of the trial is overallsurvival. It will be determined separately for arm 1 with positive methylation-status at septin9 gene and arm 2 with negative methylation-status at septin9 gene.
This survey will be done once a year routinely according to requirements of DKG-certified Darmzentrum. It will be done orally via a questionform and data will be stored at DKG-certified database kolorect.
Study Design: Allocation: ; Masking: ; Control: ; Assignment: ; Study design purpose: Prognosis
Project description:DNA methylation profiling of heterogeneous head and neck squamous cell carcinoma (HNSCC) cohorts has been reported to predict patient outcome. We investigated if a prognostic DNA methylation profile could be found in tumour tissue from a single uniform subsite, the oral tongue. The methylation status of 83 comprehensively annotated oral tongue squamous cell carcinoma (OTSCC) formalin-fixed paraffin-embedded (FFPE) samples from a single institution were examined with the Illumina HumanMethylation450K (HM450K) array. 83 FFPE primary OTSCC tumour samples were analysed in one experimental run.
Project description:MicroRNA expression profiles were sucessfully contructed in 397 patients with NSCLC and 151 corresponding adjacent noncancerous tissues using a custom microarray containing probes for 1888 miRNAs and an outcome prediction of miRNA signature was successfully identified for predicting prognosis in NSCLC.