Project description:These samples are part of the ENCODE consortium’s proposed time-limited Pilot Study for confirmation of the utility of RNA abundance measurements as a standard reference phenotyping tool. Keywords: cell type comparison For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf Each of the 7 ENCODE laboratories submitted at least one of the two Tier1 cell lines. These were processed on Affymetrix Exon 1.0 ST arrays to obtain retrospective phenotyping data for each cell line.
Project description:Introduction: MicroRNAs (miRNAs) are small, non-coding RNA molecules involved in post-transcriptional gene regulation and have recently been shown to play a role in cancer metastasis. In solid tumors, especially breast cancer, alterations in miRNA expression contribute to cancer pathogenesis, including metastasis. Considering the emerging role of miRNAs in metastasis, the identification of predictive markers is necessary to further understanding of stage-specific breast cancer development. This is a retrospective analysis that aimed to identify molecular biomarkers related to distant breast cancer metastasis development.<br><br>Methods: A retrospective case cohort study was performed in 64 breast cancer patients treated during the period from 1998-2001. The case group (n=29) consisted of patients with a poor prognosis who presented with breast cancer recurrence or metastasis during follow up. The control group (n=35) consisted of a random sample of patients with a good prognosis who did not develop breast cancer recurrence or metastasis. These patient groups were stratified according to TNM clinical stage (CS) I, II and III, and the main clinical features of the patients were homogeneous. miRNA profiling was performed using formalin-fixed, paraffin-embedded tumors. Biomarkers related to metastatic potential were identified independent of clinical stage, and a cutoff point was selected based on the optimal sensitivity and specificity (ROC curve). Finally, a hazard risk analysis of these biomarkers was performed to evaluate their relation to metastatic potential. <br><br>Results: miRNA expression profiling identified several miRNAs that were either specific and shared across all clinical stages (p?0.05). Among these, we identified miRNAs previously associated with cell motility (let-7 family), cell proliferation and invasion (hsa-miR-16 and has-miR-205) and distant metastasis (hsa-miR-21). In addition, hsa-miR-494 and hsa-miR-21 were up-regulated in metastatic cases of CSI and II. Furthermore, the combination of the 3 miRNAs identified for CSII (hsa-miR-494, hsa-miR-183 and hsa-miR-21) was significant and were a more effective risk marker compared to the single miRNAs. <br><br>Conclusions: Women with metastatic breast cancer, especially CSII, presented up-regulated levels of miR-183, miR-494 and miR-21, which were associated with a poor prognosis. These miRNAs therefore represent new risk biomarkers of breast cancer metastasis and may be useful for future targeted therapies.
Project description:DNA Methylation profiles were generated for retrospective cases to support work into investigation of the immune environment in pediatric ependymoma. Samples were analyzed using the Illumina 450k beadchip and processed using the Heidelberg classifier (v11.2b and subsequently v12.3 for subgrouping/subtyping). The aim of the study was to better understand the immune-tumor microenvironment in pediatric ependymoma and the methylation profiles support the diagnoses of each case.
Project description:These samples are part of the ENCODE consortium’s proposed time-limited Pilot Study for confirmation of the utility of RNA abundance measurements as a standard reference phenotyping tool. Keywords: cell type comparison For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf
Project description:There are ~1.4 million cases of colorectal cancer (CRC) annually worldwide. Due to recent implementation of bowel cancer screening (BCS), incidence of diagnosis with stage I (T1/2, N0, M0) CRC has increased nearly four-fold; from approximately 12% pre-screening to approximately 42-45%. While survival rates for patients diagnosed with stage I CRC remains above 95%, and identification of patients at this early stage provides the best opportunity to improve in cancer survival rates, recent data has provided quantitative evidence that metastatic seeding can occur from disseminated cells at the very earliest stage of CRC development. The aim of study was to give an insight into aggressive “born-to-be-bad” biology through generation and transcriptional profiling of a novel case-controlled retrospective T1 CRC discovery cohort. We performed transcriptional and histological profiling to identify molecular pathology features of the high-risk metastatic phenotypes, discriminating between relapse and non-relapse T1 lesions and found that a cohort of aggressive early disseminating stage 1 CRC is associated with high cell intrinsic TGFB signalling and not stromal signalling.
Project description:The discovery of novel protein biomarkers in melanoma is crucial. Our introduction of formalin-fixed paraffin embedded (FFPE) tumor protocol provides new opportunities to understand the progression of melanoma and open the possibility to screen tens of thousands of FFPE samples deposited in tumor biobanks and available at hospital pathology departments. In our retrospective pilot study, 90 FFPE samples from 77 patients were processed. Differential quantitative protein expression was performed by high resolution mass spectrometry. The protein expression profiles were correlated with the standardized dataset of histopathologic analysis, and longitudinal therapeutical meta-data.