Gene expression study in hepatocellular carcinoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE16757 | GEO | 2010/06/18
SECONDARY ACCESSION(S): PRJNA117467
REPOSITORIES: GEO
Similar Datasets
Project description:Gene expression data from 100 human hepatocellular carcinomas (HCC) were generated and analyzed as part of effort for validating prognostic gene expression signatures from previous studies. Using four different classification algorithms and leave-one-out cross-validation approaches, four different prognostic signatures were applied to test the robustness and concordance of predicted outcome in individual patients. All four tumor-derived signatures were significantly associated with prognosis and had a high rate of concordance with predicted outcomes for individual patients. Total RNA was extracted from the fresh frozen tissues of 100 HCC. Five-hundred nanograms of total RNA were used for labeling and hybridization, according to the manufacturerâs protocols (Illumina). After the bead chips were scanned with an Illumina BeadArray Reader (Illumina), the microarray data were normalized using the quantile normalization method in the Linear Models for Microarray Data package in the R language environment. The expression level of each gene was transformed into a log 2 base before further analysis.
2010-07-08 | E-GEOD-16757 | biostudies-arrayexpress
Project description:Background: Hepatocellular carcinoma (HCC) is among the top-five cancer killers worldwide. Here, we describe our analysis of 20 gene signatures with reported prognostic value in a cohort of patients with early stage HCC treated with surgical resection. Methods: We performed gene-expression profiling of 164 formalin-fixed, paraffin-embedded HCC from three hepatology centers participating the HCC Genomic Consortium. We utilized IlluminaM-bM-^@M-^Ys whole-genome DASL assay measuring ~24,000 annotated human genes. We evaluated genomic concordance and prognostic performance of 20 already reported prognostic gene signatures. Additionally, since only the largest nodule was profiled, we also excluded patients with multiple tumors to avoid biases related to intra-individual genomic tumor heterogeneity. Results: Among the 20 signatures evaluated, 15 were able to confidently allocate patients (FDR<0.05) within their predicted poor-outcome subclass. Pairwise comparisons showed a significant overlap between almost all poor-outcome signatures derived from the tumor (P<0.001), except for the metastatic HCC signature. Interestingly, poor-outcome signatures from the tumor were not significantly associated with those obtained from non-tumor adjacent tissue in the same patient. The prognosis analysis for earliest stages (BCLC 0 or A) with single nodules revealed that the G3 signature reported by Boyault et al. Conclusions: We present a composite genomic model for prediction of tumor recurrence in early HCC. It will allow risk stratification, personalized surveillance, and eventually customized interventions in patients with early HCC candidates for resection. Samples with "used for prognostic prediction: yes" were included in the study. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2011-02-17 | E-GEOD-20140 | biostudies-arrayexpress
Project description:Background: Hepatocellular carcinoma (HCC) is among the top-five cancer killers worldwide. Here, we describe our analysis of 20 gene signatures with reported prognostic value in a cohort of patients with early stage HCC treated with surgical resection. Methods: We performed gene-expression profiling of 164 formalin-fixed, paraffin-embedded HCC from three hepatology centers participating the HCC Genomic Consortium. We utilized Illumina’s whole-genome DASL assay measuring ~24,000 annotated human genes. We evaluated genomic concordance and prognostic performance of 20 already reported prognostic gene signatures. Additionally, since only the largest nodule was profiled, we also excluded patients with multiple tumors to avoid biases related to intra-individual genomic tumor heterogeneity. Results: Among the 20 signatures evaluated, 15 were able to confidently allocate patients (FDR<0.05) within their predicted poor-outcome subclass. Pairwise comparisons showed a significant overlap between almost all poor-outcome signatures derived from the tumor (P<0.001), except for the metastatic HCC signature. Interestingly, poor-outcome signatures from the tumor were not significantly associated with those obtained from non-tumor adjacent tissue in the same patient. The prognosis analysis for earliest stages (BCLC 0 or A) with single nodules revealed that the G3 signature reported by Boyault et al. Conclusions: We present a composite genomic model for prediction of tumor recurrence in early HCC. It will allow risk stratification, personalized surveillance, and eventually customized interventions in patients with early HCC candidates for resection. Samples with "used for prognostic prediction: yes" were included in the study. This SuperSeries is composed of the SubSeries listed below.
2011-02-17 | GSE20140 | GEO
Project description:The derivation of molecular signatures indicative of disease status and predictive of subsequent behavior could facilitate the optimal choice of treatment for prostate cancer patients. In this study, we conducted a computational analysis of gene expression profile data obtained from 79 cases, 39 of which were classified as having disease recurrence, to investigate whether advanced computational algorithms can derive more accurate prognostic signatures for prostate cancer. At the 90% sensitivity level, a newly derived prognostic genetic signature achieved 85% specificity. This is the first reported genetic signature to outperform a clinically used postoperative nomogram. Furthermore, a hybrid prognostic signature derived by combination of the nomogram and gene expression data significantly outperformed both genetic and clinical signatures, and achieved a specificity of 95%. Our study demonstrates the feasibility of utilizing gene expression information for highly accurate prostate cancer prognosis beyond the current clinical systems, and shows that more advanced computational modeling of tissue-derived microarray data is warranted before clinical application of molecular signatures is considered. mRNA profiling was performed using 79 cases of prostate cancer of known disease recurrence status
2010-11-05 | E-GEOD-25136 | biostudies-arrayexpress
Project description:Background Published multi-gene classifiers suggested outcome prediction for patients with stage UICC II colon cancer based on different gene expression signatures. However, there is currently no translation of these classifiers for application in routine diagnostic. Therefore, we aimed at validating own and published gene expression signatures employing methods which enable RNA and protein detection in routine diagnostic specimens. Results Immunohistochemistry was applied to 68 stage UICC II colon cancers to determine the protein expression of five selected previously published classifier genes (CDH17, LAT, CA2, EMR3, and TNFRSF11A). Correlation of protein expression data with clinical outcome within a 5-year post-surgery course failed to separate patients with a disease-free follow-up [Group DF] and relapse [Group R]). In addition, RNA from macrodissected tumor samples from 53 of these 68 patients was profiled on Affymetrix GeneChips (HG-U133 Plus 2.0). Prognostic signatures were generated by Nearest Shrunken Centroids with cross-validation. Although gene expression profiling allowed the identification of differentially expressed genes between the groups DF and R, a stable classification and prognosis signature was not discernable in our data. Furthermore, the application of previously published gene signatures consisting of 22 and 19 genes, respectively, to our gene expression data set using ‘global tests’ and leave-one-out cross-validation was unable to predict clinical outcome (prediction rate 75.5% and 64.2%; n.s.). T-stage was the only independent prognostic factor for relapse in multivariate analysis with established clinical and pathological parameters including microsatellite status. Conclusions Our protein and gene expression analyses currently do not support application of molecular classifiers for prediction of clinical outcome in routine diagnostic as a basis for patient-orientated therapy in stage UICC II colon cancer. Further studies are needed to develop prognosis signatures applicable in patient care.
2011-04-10 | GSE18088 | GEO
Project description:The derivation of molecular signatures indicative of disease status and predictive of subsequent behavior could facilitate the optimal choice of treatment for prostate cancer patients. In this study, we conducted a computational analysis of gene expression profile data obtained from 79 cases, 39 of which were classified as having disease recurrence, to investigate whether advanced computational algorithms can derive more accurate prognostic signatures for prostate cancer. At the 90% sensitivity level, a newly derived prognostic genetic signature achieved 85% specificity. This is the first reported genetic signature to outperform a clinically used postoperative nomogram. Furthermore, a hybrid prognostic signature derived by combination of the nomogram and gene expression data significantly outperformed both genetic and clinical signatures, and achieved a specificity of 95%. Our study demonstrates the feasibility of utilizing gene expression information for highly accurate prostate cancer prognosis beyond the current clinical systems, and shows that more advanced computational modeling of tissue-derived microarray data is warranted before clinical application of molecular signatures is considered.
2010-11-05 | GSE25136 | GEO
Project description:Defining molecular features that can predict the recurrence of colorectal cancer (CRC) for stage II-III patients remains challenging in cancer research. Most available clinical samples are Formalin-Fixed and Paraffin-Embedded (FFPE). NanoString nCounter® and Affymetrix GeneChip® Human Transcriptome Array 2.0 (HTA) are the two platforms marketed for high-throughput gene expression profiling for FFPE tissue samples. In this study, to identify an optimal platform for the gene expression profiling of FFPE CRC samples, we evaluated the expression of 516 genes from published frozen tissue-derived prognostic signatures in 42 CRC patient samples measured by these two platforms. Based on HTA platform-derived data, we identified both gene (99 individual genes, FDR < 0.05) and gene set (four of the six reported multi-gene signatures with sufficient information for evaluation, P < 0.05) expression differences associated with survival outcomes. Using nCounter platform-derived data, only one of the six multi-gene signatures (P < 0.05) but no individual gene was associated with survival outcomes. Therefore, the HTA appears to provide a more robust gene expression dataset using genes from published gene signatures. Our study indicated that sufficiently high quality RNA could be obtained from FFPE tumor tissues to detect frozen tissue-derived prognostic gene expression signatures for CRC patients.
2016-08-31 | GSE78248 | GEO
Project description:Lung cancer remains the leading cause of cancer death worldwide. Overall 5-year survival is about 10-15% and despite curative intent surgery, treatment failure is primarily due to recurrent disease. Conventional prognostic markers are unable to determine which patients with completely resected disease within each stage group are likely to relapse. To identify a gene signature associated with recurrent squamous cell carcinoma (SCC) of lung, we analyzed primary tumour gene expression for a total of fifty-one SCCs (stage I-III) on 22,323 element microarrays, comparing expression profiles for individuals who remained disease-free for a minimum of 36 months with those from individuals whose disease recurred within 18 months of complete resection. Cox proportional hazards modeling with leave-one-out cross-validation identified a 70-gene capable of predicting the likelihood of tumor recurrence and a 79-gene signature predictive for overall survival. These two signatures were pooled to generate a 111-gene classifier which achieved an overall predictive accuracy for disease recurrence of 72% (77% sensitivity, 67% specificity) in an independent set of fifty-eight stage I-III SCCs. This classifier also predicted differences in survival (log-rank P=0.0008, hazard ratio (HR), 3.8 [95% confidence interval, 1.6-8.7]), and was superior to conventional prognostic markers such as TNM stage or N stage in predicting patient outcome. Genome-wide profiling has revealed a distinct gene expression profile for recurrent lung SCC which may be clinically useful as a prognostic tool. Expression profiling using 22K element microarrays of 51 primary lung squamous cell carcinomas.
2010-07-01 | E-GEOD-5123 | biostudies-arrayexpress
Project description:A 36-gene classifier was constructed through expression profiling of 132 tumors from tamoxifen-treated patients using 70-mer oligonucleotide microarrays. The robustness of the signature was demonstrated using expression data from 83 independent tumors. The 36-gene signature was (i) more efficient to predict disease-free survival than the traditional histo-pathological prognostic factors, (ii) as effective as the Nottingham Prognostic Index or the "Adjuvant!" software, and (iii) the only independent prognostic factor. Comparison with several already published signatures demonstrated that the 36-gene signature was among the best to classify tumors. Keywords: Gene expression profiling; supervised analysis; molecular signature predictive of recurrence; univariate and multivariate analysis in relation to disease-free survival.
2008-03-18 | GSE9893 | GEO
Project description:Determining agreement in classification between platforms and procurement methods requires a variety of methods. We have shown that centroid-based algorithms are robust classifiers for breast cancer subtype assignment across platforms (microarray and qRT-PCR data) and procurement conditions (fresh frozen and formalin-fixed, paraffin-embedded tissues). On a gene-by-gene basis, we found that the standard deviation, dynamic range, and concordance correlation coefficient are important parameters to assess individual primer set performance across procurement methods. Our strategy for primer set validation and classification have applications in routine clinical practice for stratifying breast cancers and other tumor types Keywords: reference x sample
2007-04-20 | GSE6130 | GEO