Dataset Information

Prospective Validation of Diagnostic Tumor Biomarkers in Men Treated With Radiotherapy for Prostate Cancer.

ABSTRACT:

Background

In prior retrospective studies, we assessed a number of prostate tumor tissue biomarkers that were associated independently with the clinical outcome of men treated with radiotherapy (RT) ± androgen deprivation therapy (ADT). In this report, the associations of selected biomarkers with biochemical or clinical disease failure (BCDF) were prospectively evaluated in men with T1-T3 prostate cancer on a randomized hypofractionation trial.

Methods

Biomarkers were analyzed in 263 of 303 men randomly assigned to standard vs moderate hypofractionation. Median follow-up was 65.9 months. Archival tissue was analyzed for Ki-67 (n?=?231), MDM2 (n?=?209), p16 (n?=?195), Cox-2 (n?=?126), p53 (n?=?206), bcl2 (n?=?223), bax (n?=?210), and PKA (n?=?160). The base model for multivariable Fine-Gray regression analysis included treatment assignment and risk groups. All statistical tests were two-sided.

Results

Each biomarker was tested one at a time relative to the base model and selected for inclusion in multivariable analysis. Ki-67 (hazard ratio [HR] = 2.31, 95% confidence interval [CI] = 1.19 to 4.48, P = .01) and bcl2&bax (HR?=?2.19, 95% CI?=?1.08 to 4.46, P = .03) were statistically significantly related to higher BCDF and were independently statistically significant when considered jointly (Ki-67: HR?=?2.26, 95% CI?=?1.12 to 4.58, P = .02; bcl2&bax: HR?=?2.14, 95% CI?=?1.03 to 4.41, P = .04). At 2.5 years postradiotherapy, the C-index of Ki-67 was 73.2%, while for the base model was only 46.2%; Ki-67 was the most statistically significant when tested without bcl2&bax.

Conclusions

In this prospective multiple biomarker analysis in men with prostate cancer treated with RT±ADT, both Ki-67 and bcl2&bax were independently related to early BCDF; however, Ki-67 alone is indicated to be the most clinically meaningful by C-index analysis and is universally available.

SUBMITTER: Pollack A

PROVIDER: S-EPMC6075027 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Publications

Prospective Validation of Diagnostic Tumor Biomarkers in Men Treated With Radiotherapy for Prostate Cancer.

Pollack Alan A Kwon Deukwoo D Walker Gail G Khor Li Yan LY Horwitz Eric M EM Buyyounouski Mark K MK Stoyanova Radka R

Journal of the National Cancer Institute 20170201 2

<h4>Background</h4>In prior retrospective studies, we assessed a number of prostate tumor tissue biomarkers that were associated independently with the clinical outcome of men treated with radiotherapy (RT) ± androgen deprivation therapy (ADT). In this report, the associations of selected biomarkers with biochemical or clinical disease failure (BCDF) were prospectively evaluated in men with T1-T3 prostate cancer on a randomized hypofractionation trial.<h4>Methods</h4>Biomarkers were analyzed in ...[more]

PMID: 28376214

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Project description:BackgroundProstate cancer (PCa) represents a significant health challenge for men, and the advancement of the disease often results in a grave prognosis for patients. Therefore, the identification of biomarkers associated with the diagnosis and prognosis of PCa holds paramount importance in patient health management.MethodsThe datasets pertaining to PCa were retrieved from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was conducted to investigate the modules specifically associated with the diagnosis of PCa. The hub genes were identified using the LASSO regression analysis. The expression levels of these hub genes were further validated by qRT-PCR experiments. Receiver operating characteristic (ROC) curves and nomograms were employed as evaluative measures for assessing the diagnostic value.ResultsThe blue module identified by WGCNA exhibited a strong association with PCa. Six hub genes (SLC14A1, COL4A6, MYOF, FLRT3, KRT15, and LAMB3) were identified by LASSO regression analysis. Further verification confirmed that these six genes were significantly downregulated in tumor tissues and cells. The six hub genes and the nomogram demonstrated substantial diagnostic value, with area under the curve (AUC) values ranging from 0.754 to 0.961. Moreover, patients with low expression levels of these six genes exhibited elevated T/N pathological stage and Gleason score, implying a more advanced disease state. Meanwhile, their progression-free survival (PFS) was observed to be potentially poorer. Finally, a significant association could be observed between the expression of these genes and the dysregulation of immune cells, along with drug sensitivity.ConclusionsIn summary, our study identified six hub genes, namely SLC14A1, COL4A6, MYOF, FLRT3, KRT15, and LAMB3, which can be utilized to establish a diagnostic model for PCa. The discovery may offer potential molecular targets for clinical diagnosis and treatment of PCa.

Dataset Information

Prospective Validation of Diagnostic Tumor Biomarkers in Men Treated With Radiotherapy for Prostate Cancer.

Background

Methods

Results

Conclusions

Publications

Prospective Validation of Diagnostic Tumor Biomarkers in Men Treated With Radiotherapy for Prostate Cancer.

Similar Datasets

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