A 13-gene signature prognostic of HPV-negative OSCC: discovery and external validation
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Lohavanichbutr P
PROVIDER: S-ECPF-GEOD-41613 | biostudies-other | 2013 Mar
REPOSITORIES: biostudies-other
Similar Datasets
Project description:To identify a prognostic gene signature for patients with human papilloma virus (HPV)-negative oral squamous cell carcinomas (OSCC).Two gene expression datasets were used: a training dataset from the Fred Hutchinson Cancer Research Center (FHCRC, Seattle, WA; n = 97) and a validation dataset from the MD Anderson Cancer Center (MDACC, Houston, TX; n = 71). We applied L1/L2-penalized Cox regression models to the FHCRC data on the 131-gene signature previously identified to be prognostic in patients with OSCCs to identify a prognostic model specific for patients with high-risk HPV-negative OSCCs. The models were tested with the MDACC dataset using a receiver operating characteristic (ROC) analysis.A 13-gene model was identified as the best predictor of HPV-negative OSCC-specific survival in the training dataset. The risk score for each patient in the validation dataset was calculated from this model and dichotomized at the median. The estimated 2-year mortality (± SE) of patients with high-risk scores was 47.1% (± 9.24%) compared with 6.35% (± 4.42) for patients with low-risk scores. ROC analyses showed that the areas under the curve for the age, gender, and treatment modality-adjusted models with risk score [0.78; 95% confidence interval (CI), 0.74-0.86] and risk score plus tumor stage (0.79; 95% CI, 0.75-0.87) were substantially higher than for the model with tumor stage (0.54; 95% CI, 0.48-0.62).We identified and validated a 13-gene signature that is considerably better than tumor stage in predicting survival of patients with HPV-negative OSCCs. Further evaluation of this gene signature as a prognostic marker in other populations of patients with HPV-negative OSCC is warranted.
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Project description:OSCC is associated with substantial mortality and morbidity. In this study, we built on our previous molecular work to identify and validate a prognostic 13-gene signature that showed a higher ability than tumor stage in predicting survival for patients with HPV-negative oral squamous cell carcinoma (OSCC).
2013-03-07 | GSE41613 | GEO
Project description:OSCC is associated with substantial mortality and morbidity. In this study, we built on our previous molecular work to identify and validate a prognostic 13-gene signature that showed a higher ability than tumor stage in predicting survival for patients with HPV-negative oral squamous cell carcinoma (OSCC). We previously reported 131 genes to be associated with survival in OSCC patients. In this study, we applied L1/L2-penalized Cox regression models to the Affymetrix array data from 97 HPV-negative OSCC patients on the 131 gene to identify a model for prediction of OSCC-specific survival. We then tested the model in an independent dataset and compared to tumor stage.
2013-03-07 | E-GEOD-41613 | biostudies-arrayexpress
Project description:Background: Glioblastoma (GBM) is the most common primary malignant intracranial tumor and closely related to metabolic alteration. However, few accepted prognostic models are currently available, especially models based on metabolic genes. Methods: The transcriptome data were obtained for all of the patients diagnosed with GBM from the Gene Expression Omnibus (GEO) (training cohort, n=369) and The Cancer Genome Atlas (TCGA) (validation cohort, n=152) with the following variables: age at diagnosis, sex, follow-up and overall survival (OS). Metabolic genes according to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were contracted, and a Lasso regression model was constructed. Survival was assessed by univariate or multivariate Cox proportional hazards regression and Kaplan-Meier analysis, and an independent external validation was also conducted to examine the model. Results: There were 341 metabolic genes showed significant differences between normal brain and GBM tissues in both the training and validation cohorts, among which 56 genes were dramatically correlated to the OS of patients. Lasso regression revealed that the metabolic prognostic model was composed of 18 genes, including COX10, COMT, and GPX2 with protective effects, as well as OCRL and RRM2 with unfavorable effects. Patients classified as high-risk by the risk score from this model had markedly shorter OS than low-risk patients (P<0.0001), and this significant result was also observed in independent external validation (P<0.001). Conclusions: The prognosis of GBM was dramatically related to metabolic pathways, and our metabolic prognostic model had high accuracy and application value in predicting the OS of GBM patients.
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Project description:We report a kidney cancer tissue-based prognostic biomarker encompassing 15 genes (15G score) to classify patients into low versus high risk for recurrence after curative nephrectomy. The 15G score was independently associated with disease free survival adjusting for clinicopathologic variables as well as existing clinical risk calculators or nomograms. By improving risk stratification of patients with ccRCC, the 15G score has the capacity to facilitate selection of biopsy confirmed small renal cancers (T1a) for treatment versus surveillance; inform intensity and duration of surveillance after curative nephrectomy; and to potentially facilitate patient selection for adjuvant systemic therapy. We retrospectively identified 110 patients who underwent radical nephrectomy for ccRCC (discovery cohort). Patients who recurred were matched based on grade/stage to patients without recurrence. Capture whole transcriptome sequencing was performed on RNA isolated from archival tissue using the Illumina platform. We developed a gene-expression signature to predict recurrence/disease-free survival (DFS) using a 15-fold lasso and elastic-net regularized linear Cox model. We derived the 31-gene cell cycle progression (mxCCP) score using RNAseq data for each patient. Kaplan-Meier (KM) curves and multivariable Cox proportional hazard testing were used to validate the independent prognostic impact of the gene-expression signature on DFS, disease specific survival (DSS) and overall survival (OS) in two validation datasets (combined n=761).
2024-04-01 | GSE254566 | GEO
Project description:BackgroundNeuroblastoma is a common solid tumor originating from the sympathetic nervous system, commonly found in children, and it is one of the leading causes of tumor-related deaths in children. In addition to pathological features, molecular-level features, such as how much gene expression is present and the mutational profile, may provide useful information for the precise treatment of neuroblastoma. Transcription factors (TFs) play an important regulatory role in all aspects of cellular life activities. But there are currently no studies on transcription factor-based biomarkers of neuroblastoma prognosis, and this study is much needed.MethodsWe downloaded RNA transcriptome data and clinical data from the TARGET database to construct a prognostic model. The prognostic model was constructed by using univariate Cox analysis, LASSO, and multivariate Cox regression. We divided the patients into low-risk and high-risk groups using the median value of the risk score as the cut-off. Then, we validated the prognostic model with the dataset GSE49710.ResultsWe constructed a prognostic model consisting of eight genes (SATB1, ZNF564, SOX14, EN1, IKZF2, SLC2A4RG, FOXJ2, and ZNF521). Patients in the high-risk group had a lower survival rate than those in the low-risk group. The area under the 3-year ROC curve of the model reached 0.825, suggesting a good predictive efficacy. We performed target gene prediction for the eight transcription factors in the model using six online databases and found that TUT1 may be a target gene for transcription factor EN1 and is associated with immune infiltration.ConclusionThis prognostic model consisting of eight transcription factor-associated genes demonstrated reliable predictive efficacy. This prediction model may provide new potential targets for the treatment of neuroblastoma and personalized monitoring of neuroblastoma patients with high and low risk.
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Project description:Purpose: Tumor markers that are related to hypoxia, proliferation, DNA damage repair and stem cell-ness, have a prognostic value in advanced stage HNSCC patients when assessed individually. Here we aimed to evaluate and validate this in a multifactorial context and assess interrelation and the combined role of these biological factors in determining chemo-radiotherapy response in HPV-negative advanced HNSCC. Methods: RNA sequencing data of pre-treatment biopsy material from 197 HPV-negative advanced stage HNSCC patients treated with definitive chemoradiotherapy was analyzed. Biological parameter scores were assigned to patient samples using previously generated and described gene expression signatures. Locoregional control rates were used to assess the role of these biological parameters in radiation response and compared to distant metastasis data. Biological factors were ranked according to their clinical impact using bootstrapping methods and multivariate Cox regression analyses that included clinical variables. Multivariate Cox regression analyses comprising all biological variables were used to define their relative role among all factors when combined. Results: Only few biomarker scores correlate with each other, underscoring their independence. The different biological factors do not correlate or cluster, except for the two stem cell markers CD44 and SLC3A2 (r = 0.4, p < 0.001) and acute hypoxia prediction scores which correlated with T-cell infiltration score, CD8+ T cell abundance and proliferation scores (r = 0.52, 0.56, and 0.6, respectively with p < 0.001). Locoregional control association analyses revealed that chronic (Hazard Ratio (HR) = 3.9) and acute hypoxia (HR = 1.9), followed by stem cell-ness (CD44/SLC3A2; HR = 2.2/2.3), were the strongest and most robust determinants of radiation response. Furthermore, multivariable analysis, considering other biological and clinical factors, reveal a significant role for EGFR expression (HR = 2.9, p < 0.05) and T-cell infiltration (CD8+T-cells: HR = 2.2, p < 0.05; CD8+T-cells/Treg: HR = 2.6, p < 0.01) signatures in locoregional control of chemoradiotherapy-treated HNSCC. Conclusion: Tumor acute and chronic hypoxia, stem cell-ness, and CD8+ T-cell parameters are relevant and largely independent biological factors that together contribute to locoregional control. The combined analyses illustrate the additive value of multifactorial analyses and support a role for EGFR expression analysis and immune cell markers in addition to previously validated biomarkers. This external validation underscores the relevance of biological factors in determining chemoradiotherapy outcome in HNSCC.
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Project description:This study presents a novel network methodology to identify prognostic gene signatures. Implication networks based on prediction logic are used to construct genome-wide coexpression networks for different disease states. From the differential components associated with specific disease states, candidate genes that are co-expressed with major disease signal hallmarks are selected. From these candidate genes, top genes that are the most predictive of clinical outcome are identified using univariate Cox model and Relief algorithm. Using this approach, a 13-gene lung cancer prognosis signature was identified, which generated significant prognostic stratifications (log-rank P < 0.05) in Director's Challenge Study (n = 442).
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Project description:The aim of this study was to construct and validate a DNA repair-related gene signature for evaluating the overall survival (OS) of patients with gastric cancer (GC). Differentially expressed DNA repair genes between GC and normal gastric tissue samples obtained from the TCGA database were identified. Univariate Cox analysis was used to screen survival-related genes and multivariate Cox analysis was applied to construct a DNA repair-related gene signature. An integrated bioinformatics approach was performed to evaluate its diagnostic and prognostic value. The prognostic model and the expression levels of signature genes were validated using an independent external validation cohort. Two genes (CHAF1A, RMI1) were identified to establish the prognostic signature and patients ware stratified into high- and low-risk groups. Patients in high-risk group presented significant shorter survival time than patients in the low-risk group in both cohorts, which were verified by the ROC curves. Multivariate analysis showed that the prognostic signature was an independent predictor for patients with GC after adjustment for other known clinical parameters. A nomogram incorporating the signature and known clinical factors yielded better performance and net benefits in calibration plot and decision curve analyses. Further, the logistic regression classifier based on the two genes presented an excellent diagnostic power in differentiating early HCC and normal tissues with AUCs higher than 0.9. Moreover, Gene Set Enrichment Analysis revealed that diverse cancer-related pathways significantly clustered in the high-risk and low-risk groups. Immune cell infiltration analysis revealed that CHAF1A and RMI1 were correlated with several types of immune cell subtypes. A prognostic signature using CHAF1A and RMI1 was developed that effectively predicted different OS rates among patients with GC. This risk model provides new clinical evidence for the diagnostic accuracy and survival prediction of GC.
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Project description:Background: Recent studies have identified several molecular subgroups of medulloblastoma associated with distinct clinical outcomes; however, no robust gene signature has been established for prognosis prediction. Our objective was to construct a robust gene signature-based model to predict the prognosis of patients with medulloblastoma. Methods: Expression data of medulloblastomas were acquired from the Gene Expression Omnibus (GSE85217, n = 763; GSE37418, n = 76). To identify genes associated with overall survival (OS), we performed univariate survival analysis and least absolute shrinkage and selection operator (LASSO) Cox regression. A risk score model was constructed based on selected genes and was validated using multiple datasets. Differentially expressed genes (DEGs) between the risk groups were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and protein-protein interaction (PPI) analyses were performed. Network modules and hub genes were identified using Cytoscape. Furthermore, tumor microenvironment (TME) was evaluated using ESTIMATE algorithm. Tumor-infiltrating immune cells (TIICs) were inferred using CIBERSORTx. Results: A 13-gene model was constructed and validated. Patients classified as high-risk group had significantly worse OS than those as low-risk group (Training set: p < 0.0001; Validation set 1: p < 0.0001; Validation set 2: p = 0.00052). The area under the curve (AUC) of the receiver operating characteristic (ROC) analysis indicated a good performance in predicting 1-, 3-, and 5-year OS in all datasets. Multivariate analysis integrating clinical factors demonstrated that the risk score was an independent predictor for the OS (validation set 1: p = 0.001, validation set 2: p = 0.004). We then identified 265 DEGs between risk groups and PPI analysis predicted modules that were highly related to central nervous system and embryonic development. The risk score was significantly correlated with programmed death-ligand 1 (PD-L1) expression (p < 0.001), as well as immune score (p = 0.035), stromal score (p = 0.010), and tumor purity (p = 0.010) in Group 4 medulloblastomas. Correlations between the 13-gene signature and the TIICs in Sonic hedgehog and Group 4 medulloblastomas were revealed. Conclusion: Our study constructed and validated a robust 13-gene signature model estimating the prognosis of medulloblastoma patients. We also revealed genes and pathways that may be related to the development and prognosis of medulloblastoma, which might provide candidate targets for future investigation.
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