Abstract
In case-control profiling studies, increasing the sample size does not always improve statistical power because the variance may also be increased if samples are highly heterogeneous. For instance, tumor samples used for gene expression assay are often heterogeneous in terms of tissue composition or mechanism of progression, or both; however, such variation is rarely taken into account in expression profiles analysis. We use a prostate cancer prognosis study as an example to demonstrate that solely recruiting more patient samples may not increase power for biomarker detection at all. In response to the heterogeneity due to mixed tissue, we developed a sample selection strategy termed Stepwise Enrichment by which samples are systematically culled based on tumor content and analyzed with t-test to determine an optimal threshold for tissue percentage. The selected tissue-percentage threshold identified the most significant data by balancing the sample size and the sample homogeneity; therefore, the power is substantially increased for identifying the prognostic biomarkers in prostate tumor epithelium cells as well as in prostate stroma cells. This strategy can be generally applied to profiling studies where the level of sample heterogeneity can be measured or estimated.
Keywords: Expression profiles, Cell-type heterogeneity, Prostate cancer, Statistical power, Sample size, Stepwise enrichment
Anti-Cancer Agents in Medicinal Chemistry
Title:A Sample Selection Strategy to Boost the Statistical Power of Signature Detection in Cancer Expression Profile Studies
Volume: 13 Issue: 2
Author(s): Zhenyu Jia, Yipeng Wang, Yuanjie Hu, Christine McLaren, Yingyan Yu, Kai Ye, Xiao-Qin Xia, James A. Koziol, Waldemar Lernhardt, Michael McClelland and Dan Mercola
Affiliation:
Keywords: Expression profiles, Cell-type heterogeneity, Prostate cancer, Statistical power, Sample size, Stepwise enrichment
Abstract: In case-control profiling studies, increasing the sample size does not always improve statistical power because the variance may also be increased if samples are highly heterogeneous. For instance, tumor samples used for gene expression assay are often heterogeneous in terms of tissue composition or mechanism of progression, or both; however, such variation is rarely taken into account in expression profiles analysis. We use a prostate cancer prognosis study as an example to demonstrate that solely recruiting more patient samples may not increase power for biomarker detection at all. In response to the heterogeneity due to mixed tissue, we developed a sample selection strategy termed Stepwise Enrichment by which samples are systematically culled based on tumor content and analyzed with t-test to determine an optimal threshold for tissue percentage. The selected tissue-percentage threshold identified the most significant data by balancing the sample size and the sample homogeneity; therefore, the power is substantially increased for identifying the prognostic biomarkers in prostate tumor epithelium cells as well as in prostate stroma cells. This strategy can be generally applied to profiling studies where the level of sample heterogeneity can be measured or estimated.
Export Options
About this article
Cite this article as:
Jia Zhenyu, Wang Yipeng, Hu Yuanjie, McLaren Christine, Yu Yingyan, Ye Kai, Xia Xiao-Qin, A. Koziol James, Lernhardt Waldemar, McClelland Michael and Mercola Dan, A Sample Selection Strategy to Boost the Statistical Power of Signature Detection in Cancer Expression Profile Studies, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (2) . https://dx.doi.org/10.2174/1871520611313020004
DOI https://dx.doi.org/10.2174/1871520611313020004 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Isoflavones, their Glycosides and Glycoconjugates. Synthesis and Biological Activity
Current Organic Chemistry Recent Research Progress on Magnetic Nanocomposites with Silica Shell Structures Preparation and Nanotheranostic Applications
Recent Patents on Nanotechnology Osthole: A Multifunctional Natural Compound with Potential Anticancer, Antioxidant and Anti-inflammatory Activities
Mini-Reviews in Medicinal Chemistry Medicinal Chemistry Approaches of Controlling Gastrointestinal Side Effects of Non-Steroidal Anti-Inflammatory Drugs. Endogenous Protective Mechanisms and Drug Design
Medicinal Chemistry Hydroxytyrosol and Derivatives: Isolation, Synthesis, and Biological Properties
Current Organic Chemistry Molecular Imaging of Breast Cancer: Role of RGD Peptides
Mini-Reviews in Medicinal Chemistry Gene Expression Analysis Approach to Establish Possible Links Between Parkinson's Disease, Cancer and Cardiovascular Diseases
CNS & Neurological Disorders - Drug Targets Chemotherapy with si-RNA and Anti-Cancer Drugs
Current Drug Delivery Circulating Levels of Angiogenic Cytokines in Waldenstrom’s Macroglobulinemia: Clinical Correlations
Current Angiogenesis (Discontinued) Design and Application of Magnetic-Based Theranostic Nanoparticle Systems
Recent Patents on Biomedical Engineering (Discontinued) Targeting Cellular Proapoptotic Molecules for Developing Anticancer Agents from Marine Sources
Current Drug Targets Effective Treatment of Human Lung Cancer by Targeting Tissue Factor with a Factor VII-Targeted Photodynamic Therapy
Current Cancer Drug Targets Thirty Years of Polyamine-Related Approaches to Cancer Therapy. Retrospect and Prospect. Part 2. Structural Analogues and Derivatives
Current Drug Targets Associating Paracrine Communication to Regenerative Medicine: Search Strategies & Major Trends in Scientific and Patent Production
Recent Patents on Regenerative Medicine Investigating Drug-induced Mitochondrial Toxicity: A Biosensor to Increase Drug Safety?
Current Drug Safety Anticancer Effects of the Organosilicon Multidrug Resistance Modulator SILA 421
Anti-Cancer Agents in Medicinal Chemistry The Versatile Stress Protein Mortalin as a Chaperone Therapeutic Agent
Protein & Peptide Letters DNA Binding Mode of Transition Metal Complexes, A Relationship to Tumor Cell Toxicity
Current Medicinal Chemistry PET Imaging in Prostate Cancer: Focus on Prostate-Specific Membrane Antigen
Current Topics in Medicinal Chemistry Cellular Membranes and Lipid-Binding Domains as Attractive Targets for Drug Development
Current Drug Targets