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
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...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
-
AMI and Anabolic-Androgenic Steroids: Case Report with Systematic Review
Current Cardiology Reviews Novel Agents Aiming at Specific Molecular Targets Increase Chemosensitivity and Overcome Chemoresistance in Hematopoietic Malignancies
Current Pharmaceutical Design Tannic Acid Inhibits Proliferation, Migration, Invasion of Prostate Cancer and Modulates Drug Metabolizing and Antioxidant Enzymes
Anti-Cancer Agents in Medicinal Chemistry Membrane Transporters as Determinants of the Pharmacology of Platinum Anticancer Drugs
Current Cancer Drug Targets MicroRNAs in Cancer Gene Therapy: Another Look
Current Cancer Therapy Reviews Antitumor Activity of Oxali-Titanocene Y in Xenografted CAKI-1 Tumors in Mice
Letters in Drug Design & Discovery Radiosensitization of Prostate Cancer by Soy Isoflavones
Current Cancer Drug Targets Design and Synthesis Three Steroid-Tetraone Derivatives Using Testosterone as Chemical Tool
Letters in Organic Chemistry Indolinones as Promising Scaffold as Kinase Inhibitors: A Review
Mini-Reviews in Medicinal Chemistry Adverse Effects and Safety of Etirinotecan Pegol, a Novel Topoisomerase Inhibitor, in Cancer Treatment: A Systematic Review
Current Cancer Therapy Reviews Meet Our Editorial Board Member:
Anti-Cancer Agents in Medicinal Chemistry Flavonoids: Prospective Drug Candidates
Mini-Reviews in Medicinal Chemistry Toward the Identification of Novel Carbonic Anhydrase XIV Inhibitors using 3D-QSAR Pharmacophore Model, Virtual Screening and Molecular Docking Study
Letters in Drug Design & Discovery Targeting the Ubiquitin-Mediated Proteasome Degradation of p53 for Cancer Therapy
Current Pharmaceutical Design Induction of Antitumor Immune Responses with Recombinant Lentivector: Role of Skin Derived DCs
Current Cancer Therapy Reviews Peptide Antagonist of the Androgen Receptor
Current Pharmaceutical Design Bisphosphonates: Molecular Mechanisms of Action and Effects on Bone Cells, Monocytes and Macrophages
Current Pharmaceutical Design Chitosan Nanoparticles: An Approbative System for the Delivery of Herbal Bioactives
The Natural Products Journal Genomic Instability in Cancer: Molecular Mechanisms and Therapeutic Potentials
Current Pharmaceutical Design Prader-Willi Syndrome: Clinical Genetics and Diagnostic Aspects with Treatment Approaches
Current Pediatric Reviews