Six stroma-based RNA markers diagnostic for prostate cancer in European-Americans validated at the RNA and protein levels in patients in China.
diagnosis; Adult; Humans; prostate cancer; Male; Middle Aged; Aged; Young Adult; Gene Expression Profiling; Gene Expression Regulation; Tumor Microenvironment; Biomarkers; China; European Continental Ancestry Group/genetics; microenvironment; Prostate/pathology; Prostatic Neoplasms/*diagnosis/*genetics; race; stroma; 80 and over; Neoplastic; Tumor/*genetics
We previously analyzed human prostate tissue containing stroma near to tumor and from cancer-negative tissues of volunteers. Over 100 candidate gene expression differences were identified and used to develop a classifier that could detect nearby tumor with an accuracy of 97% (sensitivity = 98% and specificity = 88%) based on 364 independent test cases from primarily European American cases. These stroma-based gene signatures have the potential to identify cancer patients among those with negative biopsies. In this study, we used prostate tissues from Chinese cases to validate six of these markers (CAV1, COL4A2, HSPB1, ITGB3, MAP1A and MCAM). In validation by real-time PCR, four genes (COL4A2, HSPB1, ITGB3, and MAP1A) demonstrated significantly lower expression in tumor-adjacent stroma compared to normal stroma (p value
Zhu Jian-Guo; Pan Cong; Jiang Jun; Deng Mingsen; Gao Hengjun; Men Bozhao; McClelland Michael; Mercola Dan; Zhong Wei-D; Jia Zhenyu
Oncotarget
2015
2015-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.18632/oncotarget.4430" target="_blank" rel="noreferrer noopener">10.18632/oncotarget.4430</a>
Generation of "virtual" control groups for single arm prostate cancer adjuvant trials.
Humans; Male; Middle Aged; Aged; Treatment Outcome; Disease-Free Survival; *Nomograms; *Prostatectomy; Antineoplastic Agents/therapeutic use; Control Groups; Controlled Clinical Trials as Topic; Prostate/drug effects/pathology/surgery; Prostatic Neoplasms/*drug therapy/mortality/pathology/surgery; Neoplasm Recurrence; Chemotherapy; Adjuvant/*methods; Local/*drug therapy/mortality/pathology/surgery
It is difficult to construct a control group for trials of adjuvant therapy (Rx) of prostate cancer after radical prostatectomy (RP) due to ethical issues and patient acceptance. We utilized 8 curve-fitting models to estimate the time to 60%, 65%, ... 95% chance of progression free survival (PFS) based on the data derived from Kattan post-RP nomogram. The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx to develop 8 subsets of cases (reference case sets) whose observed PFS times were most accurately predicted by each model. To prepare a virtual control group for a single-arm adjuvant Rx trial, we first select the optimal model for the trial cases based on the minimum weighted Euclidean distance between the trial case set and the reference case set in terms of clinical features, and then compare the virtual PFS times calculated by the optimum model with the observed PFSs of the trial cases by the logrank test. The method was validated using an independent dataset of 155 post-RP patients without adjuvant Rx. We then applied the method to patients on a Phase II trial of adjuvant chemo-hormonal Rx post RP, which indicated that the adjuvant Rx is highly effective in prolonging PFS after RP in patients at high risk for prostate cancer recurrence. The method can accurately generate control groups for single-arm, post-RP adjuvant Rx trials for prostate cancer, facilitating development of new therapeutic strategies.
Jia Zhenyu; Lilly Michael B; Koziol James A; Chen Xin; Xia Xiao-Qin; Wang Yipeng; Skarecky Douglas; Sutton Manuel; Sawyers Anne; Ruckle Herbert; Carpenter Philip M; Wang-Rodriguez Jessica; Jiang Jun; Deng Mingsen; Pan Cong; Zhu Jian-Guo; McLaren Christine E; Gurley Michael J; Lee Chung; McClelland Michael; Ahlering Thomas; Kattan Michael W; Mercola Dan
PloS one
2014
1905-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1371/journal.pone.0085010" target="_blank" rel="noreferrer noopener">10.1371/journal.pone.0085010</a>