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A Gleason score-related outcome model for human prostate cancer: a comprehensive study based on weighted gene co-expression network analysis.

ABSTRACT: Background:Prostate cancer (PCa) is the second leading cause of cancer death in men in 2018. Thus, the evaluation of prognosis is crucial for clinical treatment decision of human PCa patients. We aim to establishing an effective and reliable model to predict the outcome of PCa patients. Methods:We first identified differentially expressed genes between prostate cancer and normal prostate in TCGA-PRAD and then performed WGCNA to initially identify the candidate Gleason score related genes. Then, the candidate genes were applied to construct a LASSO Cox regression analysis model. Numerous independent validation cohorts, time-dependent receiver operating characteristic (ROC), univariate cox regression analysis, nomogram were used to test the effectiveness, accuracy and clinical utility of the prognostic model. Furthermore, functional analysis and immune cells infiltration were performed. Results:Gleason score-related differentially expressed candidates were identified and used to build up the outcome model in TCGA-PRAD cohort and was validated in MSKCC cohort. We found the 3-gene outcome model (CDC45, ESPL1 and RAD54L) had good performance in predicting recurrence free survival, metastasis free survival and overall survival of PCa patients. Time-dependent ROC and nomogram indicated an ideal predictive accuracy and clinical utility of the outcome model. Moreover, outcome model was enriched in 28 pathways by GSVA and GSEA. In addition, the risk score was positively correlated with memory B cells, native CD4 T cells, activated CD4 memory T cells and eosinophil, and negatively correlated with plasma cells, resting CD4 memory T cells, resting mast cells and neutrophil. Conclusions:In summary, our outcome model proves to be an effective prognostic model for predicting the risk of prognosis in PCa.

SUBMITTER: Wang Y

PROVIDER: S-EPMC7216484 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A Gleason score-related outcome model for human prostate cancer: a comprehensive study based on weighted gene co-expression network analysis.

Wang Yongzhi Y Yang Zhonghua Z

Cancer cell international 20200511

<h4>Background</h4>Prostate cancer (PCa) is the second leading cause of cancer death in men in 2018. Thus, the evaluation of prognosis is crucial for clinical treatment decision of human PCa patients. We aim to establishing an effective and reliable model to predict the outcome of PCa patients.<h4>Methods</h4>We first identified differentially expressed genes between prostate cancer and normal prostate in TCGA-PRAD and then performed WGCNA to initially identify the candidate Gleason score relate ...[more]

PMID: 32425694

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Project description:BackgroundProstate tumor volume predicts biochemical recurrence, metastases, and tumor proliferation. A recent study showed that prostate tumor eccentricity (elongation or roundness) correlated with Gleason score. No studies examined the relationship among the prostate tumor's shape, volume, and potential aggressiveness.MethodsOf the 26 patients that were analyzed, 18 had volumes >1 cc for the histology-based study, and 25 took up contrast material for the MRI portion of this study. This retrospective study quantitatively compared tumor eccentricity and volume measurements from pathology assessment sectioned wholemount prostates and multi-parametric MRI to Gleason scores. Multi-parametric MRI (T1, T2, diffusion, dynamic contrast-enhanced images) were resized, translated, and stitched to form spatially registered multi-parametric cubes. Multi-parametric signatures that characterize prostate tumors were inserted into a target detection algorithm (Adaptive Cosine Estimator, ACE). Various detection thresholds were applied to discriminate tumor from normal tissue. Pixel-based blobbing, and labeling were applied to digitized pathology slides and threshold ACE images. Tumor volumes were measured by counting voxels within the blob. Eccentricity calculation used moments of inertia from the blobs.ResultsFrom wholemount prostatectomy slides, fitting two sets of independent variables, prostate tumor eccentricity (largest blob eccentricity, weighted eccentricity, filtered weighted eccentricity) and tumor volume (largest blob volume, average blob volume, filtered average blob volume) to Gleason score in a multivariate analysis, yields correlation coefficient R=0.798 to 0.879 with P<0.01. The eccentricity t-statistic exceeded the volume t-statistic. Fitting histology-based total prostate tumor volume against Gleason score yields R=0.498, P=0.0098. From multi-parametric MRI, the correlation coefficient R between the Gleason score and the largest blob eccentricity for varying thresholds (0.30 to 0.55) ranged from -0.51 to -0.672 (P<0.01). For varying thresholds (0.60 to 0.80) for MRI detection, the R between the largest blob volume eccentricity against the Gleason score ranged from 0.46 to 0.50 (P<0.03). Combining tumor eccentricity and tumor volume in multivariate analysis failed to increase Gleason score prediction.ConclusionsProstate tumor eccentricity, determined by histology or MRI, more accurately predicted Gleason score than prostate tumor volume. Combining tumor eccentricity with volume from histology-based analysis enhanced Gleason score prediction, unlike MRI.

Dataset Information

A Gleason score-related outcome model for human prostate cancer: a comprehensive study based on weighted gene co-expression network analysis.

Publications

A Gleason score-related outcome model for human prostate cancer: a comprehensive study based on weighted gene co-expression network analysis.

Similar Datasets

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