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
-
Cannabinoids, Immune System and Cytokine Network
Current Pharmaceutical Design Tubulins as Therapeutic Targets in Cancer: from Bench to Bedside
Current Pharmaceutical Design Cancer and Treatment Modalities
Current Cancer Therapy Reviews Potential Anticancer Properties of Bisphosphonates: Insights From Preclinical Studies
Anti-Cancer Agents in Medicinal Chemistry Decoding the Knots of Initiation of Oncogenic Epithelial-Mesenchymal Transition in Tumor Progression
Current Cancer Drug Targets Endocannabinoids as Regulators of Transient Receptor Potential (TRP)Channels: a Further Opportunity to Develop New Endocannabinoid-Based Therapeutic Drugs
Current Medicinal Chemistry Insights into Immunophilin Structure and Function
Current Medicinal Chemistry Pharmacokinetics of Darolutamide, its Diastereomers and Active Metabolite in the Mouse: Response to Saini NK et al. (2020)
Drug Metabolism Letters Conjugates of Natural Compounds with Nitroxyl Radicals as a Basis for Creation of Pharmacological Agents of New Generation
Current Medicinal Chemistry Growth Retardation in Children with Celiac Disease
Current Pediatric Reviews Recent Advances in Artemisinin Production Through Heterologous Expression
Current Medicinal Chemistry Radioiodination of Pimonidazole as a Novel Theranostic Hypoxia Probe
Current Radiopharmaceuticals Cancer Stem Cells in Pediatric Brain Tumors
Current Stem Cell Research & Therapy Recombinant Human Insulin-Like Growth Factor-1: A New Cardiovascular Disease Treatment Option?
Cardiovascular & Hematological Agents in Medicinal Chemistry Targeted Drug Delivery for Breast Cancer Treatment
Recent Patents on Anti-Cancer Drug Discovery VEGF/VEGFR2 Autocrine Signaling Stimulates Metastasis in Prostate Cancer Cells
Current Angiogenesis (Discontinued) Structure Activity Relationship of Arylidene Pyrrolo and Pyrido [2,1-b] Quinazolones as Cytotoxic Agents: Synthesis, SAR Studies, Biological Evaluation and Docking Studies
Medicinal Chemistry Ras Family Small GTPase-Mediated Neuroprotective Signaling in Stroke
Central Nervous System Agents in Medicinal Chemistry Understanding the Molecular Properties and Metabolism of Top Prescribed Drugs
Current Topics in Medicinal Chemistry Pro-apoptotic Activity of BH3-only Proteins and BH3 Mimetics: from Theory to Potential Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry