Project description:Background. Current clinicopathological factors are not accurate enough to predict tumor progression in intermediate/high-risk clear cell renal cell carcinoma (ccRCC). Objective: To develop a prognostic classifier for intermediate/high-risk ccRCC based on gene expression and histopathological prognostic factors. Design, setting and participants: Retrospective, multicenter study including 84 intermediate/high-risk ccRCC patients who underwent surgery. Global gene expression patterns were analyzed in 13 tissue samples from progressive and non-progressive ccRCC using Illumina Hi-seq 2000 kit. Expression levels of 22 selected genes were assessed by nCounter Analysis in an independent series of 71 ccRCC. A combined genetic-clinicopathological classifier for predicting tumor progression was developed. Outcomes measurements and statistical analysis: Logistic regression analysis was used to identify independent prognostic factors. Results and Limitations: A total of 1202 genes were found differentially expressed between progressive and non-progressive intermediate/high-risk ccRCC. In the independent cohort, 7 genes remained significant differentially expressed between the groups. Expression of HS6ST2, pT stage, tumor size and ISUP grade were found independent prognostic factors for tumor progression (p<0.05). A risk score generated using these variables was able to distinguish a subset of patients at higher-risk of progression (HR 7,27; p<0,001), improving the individual discriminative performance of each of these variables on their own. Conclusions: A novel prognostic algorithm based on genetic and clinicopathological factors was successfully developed. This model may aid physicians to select high-risk patients for further adjuvant target therapy or immune therapy.
Project description:To date, there are no known prognostic markers identified in patients with fusion gene-negative rhabdomyosarcoma. This study validates the 5-gene (MG5) signature as a prognostic marker in patients with fusion negative intermediate-risk rhabdomyosarcoma clearly stratifying this otherwise clinically homogenous population of patients into two risk groups based on outcome. In addition, this analysis was performed using nCounter assay on paraffin embedded tissues and the results were concordant to previously published results using frozen tissues in a different patient cohort. Therefore, this work holds tremendous translational relevance as the MG5 signature can be reliably assessed in readily available paraffin embedded tissues of fusion gene-negative rhabdomyosarcoma patients in prospective clinical trials to stratify them into prognostic risk groups as well as to potentially tailor future therapy based on these risk groups.
Project description:Gleason grading is an important prognostic indicator for prostate adenocarcinoma and is crucial for patient treatment decisions. However, intermediate-risk patients diagnosed in Gleason Grade Groups (GG) 2 and GG3 can harbour either aggressive or non-aggressive disease, resulting in under- or over-treatment of a significant number of patients. Here, we performed proteomic, differential expression, machine learning, and survival analyses for 1,348 matched tumour and benign samples from 278 patients. Three proteins (F5, TMEM126B and EARS2) were identified as candidate biomarkers in patients with biochemical recurrence. Multivariate Cox regression yielded 18 proteins, from which a risk score was constructed to dichotomise prostate cancer patients into low- and high-risk groups. This 18-protein signature is prognostic for the risk of biochemical recurrence and completely independent of the intermediate GG. Our results suggest that markers generated by computational proteomic profiling have the potential for clinical applications including integration into prostate cancer management.
Project description:Prognostic classifier to identify intermediate and high-risk clear-cell renal cell carcinoma patients at higher risk for tumor progression
Project description:Molecular prognostic assays, such as Oncotype DX, are increasingly incorporated into the management of patients with invasive breast carcinoma. BreastPRS is a new molecular assay developed and validated from a meta-analysis of publically available genomic datasets. We applied the assay to matched fresh-frozen (FF) and formalin-fixed paraffin embedded (FFPE) tumor samples to translate the assay to FFPE. A linear relationship of the BreastPRS prognostic score was observed between tissue preservation formats. BreastPRS recurrence scores were compared with Oncotype DX recurrence scores from 246 patients with invasive breast carcinoma and known Oncotype DX results. Using this series, a 120-gene linear discriminant algorithm (LDA) was trained to predict Oncotype DX risk groups and then applied to series of untreated, node-negative, estrogen receptor (ER) – positive patients from previously published studies with known clinical outcomes. Correlation of recurrence score and risk group between Oncotype DX and BreastPRS was statistically significant (P<0.0001). 59 of 260 (23%) patients from four previously published studies were classified as intermediate-risk when the 120-gene LDA was applied. BreastPRS reclassified the 59 patients into binary risk groups (high vs. low-risk). 23 (39%) patients were classified as low-risk 36 (61%) as high-risk [P=0.029, HR: 3.64, 95% CI: 1.40 to 9.50]. At 10 years from diagnosis, the low-risk group had a 90% recurrence-free survival (RFS) rate, compared to 60% for the high-risk group. BreastPRS recurrence score is comparable to Oncotype DX and can reclassify Oncotype DX intermediate-risk patients into two groups with significant differences in RFS. Further studies are needed to validate these findings. Expression profiles of 246 invasive breast carcinomas.
Project description:The primary objective of this study was to correlate genetic alterations from Hh pathway genes with biochemical free relapse rate. aCGH data of 126 intermediate risk men with histologically confirmed adenocarcinoma of the prostate who had chosen radical radiotherapy as their primary treatment between 1996-2006.
Project description:Radical prostatectomy (RP) is a primary treatment option for men with intermediate- and high-risk prostate cancer. Although many are effectively cured with local therapy alone, these men are by definition at higher risk of adverse pathologic features. It has been shown previously that genomic data can be used to predict tumor aggressiveness. Our objective was to evaluate genomic data and it's relationship to pathological stage and grade in a cohort of men that received no treatment other than radical prostatectomy surgery.
Project description:DNA methylation profiles were compared between gastric mucosae samples without Helicobacter pylori (HP) infection (low risk : G1), those with HP eradication without gastric cancer (intermediate risk : G2), and those with HP eradication with gastric cancer (high risk : G3).
Project description:The molecular profile of endometrial cancer has become an important tool in determining patient prognosis and their optimal adjuvant treatment. In addition to The Cancer Genome Atlas (TCGA), simpler tools have been developed, such as the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE). We attempted to determine a genetic signature to build a recurrence risk score in patients diagnosed with low- and intermediate-risk endometrial cancer. A case-control study was conducted. The eligible patients were women diagnosed with recurrence low- and intermediate-risk endometrial cancer between January 2009 and December 2014 at a single institution; the recurrence patients were matched to two nonrecurrence patients with the same diagnosis by age and surgical staging. Following RNA isolation of 51 cases, 17 recurrence and 34 nonrecurrence patients, the expression profile was determined using the nCounter® PanCancer Pathways Panel, which contains 770 genes. The expression profile was successfully characterized in 49/51 (96.1%) cases. We identified 12 genes differentially expressed between the recurrence and nonrecurrence groups. The ROC curve for each gene was generated, and all had AUCs higher than 0.7. After backward stepwise logistic regression, four genes were highlighted: FN1, DUSP4, LEF1, and SMAD9. The recurrence risk score was calculated, leading to a ROC curve of the 4-gene model with an AUC of 0.93, sensitivity of 100%, and specificity of 72.7%. We identified a four-gene signature that is associated the risk of recurrence in patients with low- and intermediate-risk endometrial cancer. This finding suggests a new prognostic factor in this poorly explored group of patients with endometrial cancer.