Sample Size Calculation for Single-Arm Phase 2 Prostate Cancer Trials.
Funding Source; Data Analysis; Study Design; Structural Equation Modeling; Prostatectomy; Statistical; Radical; Sample Size Determination; World Wide Web Applications; Prostatic Neoplasms – Therapy
Jia Zhenyu; Xiao Xu; Koziol James; Wei-De Zhong
Personalized Medicine in Oncology
2015
2015-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
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>
The identification of trans-associations between prostate cancer GWAS SNPs and RNA expression differences in tumor-adjacent stroma.
Humans; Male; Risk Factors; Genetic Predisposition to Disease; Genome-Wide Association Study; Prostatic Neoplasms/*genetics/metabolism; RNA/*biosynthesis/genetics; Polymorphism; Single Nucleotide
Here we tested the hypothesis that SNPs associated with prostate cancer risk, might differentially affect RNA expression in prostate cancer stroma. The most significant 35 SNP loci were selected from Genome Wide Association (GWA) studies of \textasciitilde40,000 patients. We also selected 4030 transcripts previously associated with prostate cancer diagnosis and prognosis. eQTL analysis was carried out by a modified BAYES method to analyze the associations between the risk variants and expressed transcripts jointly in a single model. We observed 47 significant associations between eight risk variants and the expression patterns of 46 genes. This is the first study to identify associations between multiple SNPs and multiple in trans gene expression differences in cancer stroma. Potentially, a combination of SNPs and associated expression differences in prostate stroma may increase the power of risk assessment for individuals, and for cancer progression.
Chen Xin; McClelland Michael; Jia Zhenyu; Rahmatpanah Farah B; Sawyers Anne; Trent Jeffrey; Duggan David; Mercola Dan
Oncotarget
2015
2015-01
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.2763" target="_blank" rel="noreferrer noopener">10.18632/oncotarget.2763</a>
A class of genes in the HER2 regulon that is poised for transcription in breast cancer cell lines and expressed in human breast tumors.
Humans; Cell Line; *Gene Expression Regulation; Reverse Transcriptase Polymerase Chain Reaction; *Gene Expression Profiling; Breast Neoplasms/genetics/pathology; Gene Regulatory Networks; Homeodomain Proteins/genetics/metabolism; MCF-7 Cells; Nanog Homeobox Protein; Neoplastic Stem Cells/metabolism; Octamer Transcription Factor-3/genetics/metabolism; Regulon/*genetics; RNA Polymerase II/metabolism; SOXB1 Transcription Factors/genetics/metabolism; Tumor Microenvironment/genetics; Receptor; Blotting; Western; Tumor; Neoplastic; ErbB-2/*genetics/metabolism
HER2-positive breast cancer accounts for 25% of all cases and has a poor prognosis. Although progress has been made in understanding signal transduction, little is known of how HER2 achieves gene regulation. We performed whole genome expression analysis on a HER2(+) and HER2(-) breast cancer cell lines and compared these results to expression in 812 primary tumors stratified by their HER2 expression level. Chip-on-chip with anti-RNA polymerase II was compared among breast cancer cell lines to identify genes that are potentially activated by HER2. The expression levels of these HER2-dependent POL II binding genes were determined for the 812 HER2+/- breast cancer tissues. Genes differentially expressed between HER2+/- cell lines were generally regulated in the same direction as in breast cancer tissues. We identified genes that had POLII binding in HER2(+) cell lines, but without significant gene expression. Of 737 such genes "poised" for expression in cell lines, 113 genes were significantly differentially expressed in breast tumors in a HER2-dependent manner. Pathway analysis of these 113 genes revealed that a large group of genes were associated with stem cell and progenitor cell control as indicated by networks centered on NANOG, SOX2, OCT3/4. HER2 directs POL II binding to a large number of genes in breast cancer cells. A "poised" class of genes in HER2(+) cell lines with POLII binding and low RNA expression but is differentially expressed in primary tumors, strongly suggests a role of the microenvironment and further suggests a role for stem cells proliferation in HER2-regulated breast cancer tissue.
Rahmatpanah Farah B; Jia Zhenyu; Chen Xin; Char Jessica E; Men Bozhao; Franke Anna-Clara; Jones Frank E; McClelland Michael; Mercola Dan
Oncotarget
2015
2015-01
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.2676" target="_blank" rel="noreferrer noopener">10.18632/oncotarget.2676</a>
Alterations in gene array patterns in dendritic cells from aged humans.
Adult; Female; Humans; Male; Aged; Young Adult; Immunity; Cluster Analysis; Age Factors; Gene Expression Regulation; *Gene Expression Profiling; *Transcriptome; Adaptive Immunity/genetics; Antigen-Presenting Cells/immunology/metabolism; Dendritic Cells/immunology/*metabolism; G1 Phase; Healthy Volunteers; 80 and over; Innate/genetics
Dendritic cells (DCs) are major antigen-presenting cells that play a key role in initiating and regulating innate and adaptive immune responses. DCs are critical mediators of tolerance and immunity. The functional properties of DCs decline with age. The purpose of this study was to define the age-associated molecular changes in DCs by gene array analysis using Affymatrix GeneChips. The expression levels of a total of 260 genes (1.8%) were significantly different (144 down-regulated and 116 upregulated) in monocyte-derived DCs (MoDCs) from aged compared to young human donors. Of the 260 differentially expressed genes, 24% were down-regulated by more than 3-fold, suggesting that a large reduction in expression occurred for a notable number of genes in the aged. Our results suggest that the genes involved in immune response to pathogens, cell migration and T cell priming display significant age-related changes. Furthermore, downregulated genes involved in cell cycle arrest and DNA replication may play a critical role in aging-associated genetic instability. These changes in gene expression provide molecular based evidence for age-associated functional abnormalities in human DCs that may be responsible for the defects in adaptive immunity observed in the elderly.
Cao Jia-ning; Agrawal Anshu; Sharman Edward; Jia Zhenyu; Gupta Sudhir
PloS one
2014
1905-7
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.0106471" target="_blank" rel="noreferrer noopener">10.1371/journal.pone.0106471</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>
A note regarding problems with interaction and varying block sizes in a comparison of endotracheal tubes.
*Randomized Controlled Trials as Topic; *Research Design; Algorithms; Anesthesiology/*methods; Data Interpretation; Humans; Intratracheal/*instrumentation; Intubation; Models; Sample Size; Statistical; Treatment Outcome
A randomized clinical experiment to compare two types of endotracheal tubes utilized a block design where each of the six participating anesthesiologists performed tube insertions for an equal number of patients for each type of tube. Five anesthesiologists intubated at least three patients with each tube type, but one anesthesiologist intubated only one patient per tube type. Overall, one type of tube outperformed the other on all three effectiveness measures. However, analysis of the data using an interaction model gave conflicting and misleading results, making the tube with the better performance appear to perform worse. This surprising result was caused by the undue influence of the data for the anesthesiologist who intubated only two patients. We therefore urge caution in interpreting results from interaction models with designs containing small blocks.
Einsporn Richard L; Jia Zhenyu
Computational and mathematical methods in medicine
2014
1905-7
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/10.1155/2014/956917" target="_blank" rel="noreferrer noopener">10.1155/2014/956917</a>
Establishing reliable miRNA-cancer association network based on text-mining method.
Algorithms; Area Under Curve; Computational Biology/*methods; Data Mining/*methods; False Positive Reactions; Gene Expression Profiling/methods; Gene Expression Regulation; Gene Regulatory Networks; Humans; MicroRNAs/*genetics/*metabolism; Neoplasms/*genetics/metabolism; Neoplastic; Probability; Reproducibility of Results
Associating microRNAs (miRNAs) with cancers is an important step of understanding the mechanisms of cancer pathogenesis and finding novel biomarkers for cancer therapies. In this study, we constructed a miRNA-cancer association network (miCancerna) based on more than 1,000 miRNA-cancer associations detected from millions of abstracts with the text-mining method, including 226 miRNA families and 20 common cancers. We further prioritized cancer-related miRNAs at the network level with the random-walk algorithm, achieving a relatively higher performance than previous miRNA disease networks. Finally, we examined the top 5 candidate miRNAs for each kind of cancer and found that 71% of them are confirmed experimentally. miCancerna would be an alternative resource for the cancer-related miRNA identification.
Li Lun; Hu Xingchi; Yang Zhaowan; Jia Zhenyu; Fang Ming; Zhang Libin; Zhou Yanhong
Computational and mathematical methods in medicine
2014
1905-7
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/10.1155/2014/746979" target="_blank" rel="noreferrer noopener">10.1155/2014/746979</a>
Weighted Lin-Wang tests for crossing hazards.
*Survival Analysis; Algorithms; Animal; Animals; Computer Simulation; Data Interpretation; Disease Models; Humans; Kaplan-Meier Estimate; Leukemia/drug therapy; Mice; Models; Reproducibility of Results; Statistical
Lin and Wang have introduced a quadratic version of the logrank test, appropriate for situations in which the underlying survival distributions may cross. In this note, we generalize the Lin-Wang procedure to incorporate weights and investigate the performance of Lin and Wang's test and weighted versions in various scenarios. We find that weighting does increase statistical power in certain situations; however, none of the procedures was dominant under every scenario.
Koziol James A; Jia Zhenyu
Computational and mathematical methods in medicine
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/10.1155/2014/643457" target="_blank" rel="noreferrer noopener">10.1155/2014/643457</a>
Role of the adjacent stroma cells in prostate cancer development and progression: synergy between TGF-beta and IGF signaling.
Androgens/metabolism; Animals; Disease Progression; Epithelial Cells/cytology; Estrogen/metabolism; Estrogens/metabolism; Humans; Male; Mice; Prostate/metabolism; Prostatic Neoplasms/*metabolism; Receptors; Signal Transduction; Somatomedins/*metabolism; Stromal Cells/*cytology; Transforming Growth Factor beta/*metabolism
This review postulates the role of transforming growth factor-beta (TGF-beta) and insulin-like growth factor (IGF-I/IGF-II) signaling in stromal cells during prostate carcinogenesis and progression. It is known that stromal cells have a reciprocal relationship to the adjacent epithelial cells in the maintenance of structural and functional integrity of the prostate. An interaction between
Lee Chung; Jia Zhenyu; Rahmatpanah Farah; Zhang Qiang; Zi Xiaolin; McClelland Michael; Mercola Dan
BioMed research international
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/10.1155/2014/502093" target="_blank" rel="noreferrer noopener">10.1155/2014/502093</a>
Advances in statistical medicine.
*Statistics as Topic; Biotechnology/trends; Computers; Decision Trees; Drug Design; Humans; Medical Informatics/*methods; Models; Neoplasms/therapy; Statistical
Datta Sujay; Xia Xiao-Qin; Bhattacharjee Samsiddhi; Jia Zhenyu
Computational and mathematical methods in medicine
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/10.1155/2014/316153" target="_blank" rel="noreferrer noopener">10.1155/2014/316153</a>
A gradient boosting algorithm for survival analysis via direct optimization of concordance index.
*Survival Analysis; Algorithms; Artificial Intelligence; Breast Neoplasms/*epidemiology/*mortality; Clinical; Databases; Decision Support Systems; Factual; Female; Humans; Internet; Models; Prognosis; Proportional Hazards Models; Software; Theoretical
Survival analysis focuses on modeling and predicting the time to an event of interest. Many statistical models have been proposed for survival analysis. They often impose strong assumptions on hazard functions, which describe how the risk of an event changes over time depending on covariates associated with each individual. In particular, the prevalent proportional hazards model assumes that covariates are multiplicatively related to the hazard. Here we propose a nonparametric model for survival analysis that does not explicitly assume particular forms of hazard functions. Our nonparametric model utilizes an ensemble of regression trees to determine how the hazard function varies according to the associated covariates. The ensemble model is trained using a gradient boosting method to optimize a smoothed approximation of the concordance index, which is one of the most widely used metrics in survival model performance evaluation. We implemented our model in a software package called GBMCI (gradient boosting machine for concordance index) and benchmarked the performance of our model against other popular survival models with a large-scale breast cancer prognosis dataset. Our experiment shows that GBMCI consistently outperforms other methods based on a number of covariate settings. GBMCI is implemented in R and is freely available online.
Chen Yifei; Jia Zhenyu; Mercola Dan; Xie Xiaohui
Computational and mathematical methods in medicine
2013
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/10.1155/2013/873595" target="_blank" rel="noreferrer noopener">10.1155/2013/873595</a>
Reanalyses of Turkington et al. (2014): Correcting Errors and Clarifying Findings.
Sivec Harry J; Hewit Michael; Jia Zhenyu; Montesano Vicki; Munetz Mark R; Kingdon David
The Journal of nervous and mental disease
2015
2015-12
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/10.1097/NMD.0000000000000402" target="_blank" rel="noreferrer noopener">10.1097/NMD.0000000000000402</a>
Patient Insurance Profiles: A Tertiary Care Compared to Three Freestanding Emergency Departments.
Emergency Service; Emergency Service – Statistics and Numerical Data; freestanding emergency department; Health – Statistics and Numerical Data; Health – Trends; Health/*statistics & numerical data/trends; Hospital/*statistics & numerical data; Hospitals; Human; Humans; insurance; Insurance; Medicaid – Statistics and Numerical Data; Medicaid/statistics & numerical data; Medically Uninsured – Statistics and Numerical Data; Medically Uninsured/statistics & numerical data; Medicare – Statistics and Numerical Data; Medicare/statistics & numerical data; Retrospective Design; Retrospective Studies; Special – Statistics and Numerical Data; Tertiary Care Centers/statistics & numerical data; United States; Urban – Statistics and Numerical Data; Urban/*statistics & numerical data
BACKGROUND: It has been speculated that freestanding emergency departments (FEDs) draw more affluent, better-insured patients away from urban hospital EDs. It is believed that this leaves urban hospital-based EDs less financially secure. OBJECTIVE: We examined whether the distribution of patients with four types of insurance (self-pay, Medicaid, Medicare, and private) at the main ED changed after opening three affiliated FEDs, and whether the insurance type distribution was different between main ED and FEDs and between individual FEDs. METHODS: A retrospective analysis of insurance status of all patients presenting to our EDs from July 2006 through August 2013. Insurance was divided into self-pay, Medicare, Medicaid, and private insurance across three time periods, which reflect the sequential opening of each FED. Insurance types for each facility were compared for individual time periods and across time periods. chi(2) was used to analyze the data. RESULTS: In the three studied time frames (periods B, C, and D), there were less privately insured patients and more self-pay, Medicaid, and Medicare patients at the main than at each FED (p \textless 0.001). Insurance types were significantly different between each of the three FEDs and the main ED (p \textless 0.001) and between each of the three FEDs (p \textless 0.001). CONCLUSIONS: There were less privately insured patients and more self-pay, Medicaid, and Medicare patients at the main ED compared to the FEDs. Privately insured patients decreased at both the FEDs and main ED during the study. Insurance distribution was significantly different between the main ED, and three FEDs, and between individual FEDs.
Simon Erin L; Griffin Gregory; Orlik Kseniya; Jia Zhenyu; Hayslip Dave; Kobe Daniel; Jouriles Nicholas
The Journal of emergency medicine
2016
2016-10
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/10.1016/j.jemermed.2016.05.058" target="_blank" rel="noreferrer noopener">10.1016/j.jemermed.2016.05.058</a>
A comparison of acuity levels between 3 freestanding and a tertiary care ED.
*Severity of Illness Index; *Tertiary Care Centers; Ambulatory Care Facilities – Administration; Ambulatory Care Facilities/*organization & administration; Emergency Service; Emergency Service – Administration; Hospital/*organization & administration; Hospitals; Human; Humans; Retrospective Design; Retrospective Studies; Scales; Severity of Illness Indices; Special; Urban – Administration; Urban/*organization & administration
INTRODUCTION: Freestanding emergency departments (FEDs) have grown in popularity. They often provide emergent care in areas distant from other EDs. Investigations and research to characterize the operation and dynamics of FEDs are needed. This study characterizes the severity of illness seen at FEDs and compares it with a hospital-based urban tertiary care ED using the emergency severity index (ESI), a quantification of patient acuity. METHODS: Patient ESI levels were analyzed retrospectively over 1 year for a single hospital system with 1 main urban hospital-based ED and 3 FEDs. Data analysis was completed using analysis of variance with and without time as a factor. RESULTS: The average ESI level at the main ED (3.04) was lower than the FEDs, respectively (3.42, 3.22, and 3.38) (P \textless .001). Patient ESI levels were significantly different between FEDs (P \textless .001). CONCLUSION: The main ED demonstrated lower ESI levels and thus higher acuity than the 3 affiliated FEDs. There were significantly different acuity levels between the main ED and 3 FEDs as well as between individual FEDs.
Simon Erin L; Kovacs Mitch; Jia Zhenyu; Hayslip Dave; Orlik Kseniya; Jouriles Nicholas
The American journal of emergency medicine
2015
2015-04
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/10.1016/j.ajem.2015.01.021" target="_blank" rel="noreferrer noopener">10.1016/j.ajem.2015.01.021</a>