Investigating Multi-cancer Biomarkers and Their Cross-predictability in the Expression Profiles of Multiple Cancer Types

Microarray technology has been widely applied to the analysis of many malignancies, however, integrative analyses across multiple studies are rarely investigated. In this study we performed a meta-analysis on the expression profiles of four published studies analyzing organ donor, benign tissues adjacent to tumor and tumor tissues from liver, prostate, lung and bladder samples. We identified 99 distinct multi-cancer biomarkers in the comparison of all three tissues in liver and prostate and 44 in the comparison of normal versus tumor in liver, prostate and lung. The bladder samples appeared to have a different list of biomarkers from the other three cancer types. The identified multi-cancer biomarkers achieved high accuracy similar to using whole genome in the within-cancer-type prediction. They also performed superior than the one using whole genome in inter-cancer-type prediction. To test the validity of the multi-cancer biomarkers, 23 independent prostate cancer samples were evaluated and 96% accuracy was achieved in inter-study prediction from the original prostate, liver and lung cancer data sets respectively. The result suggests that the compact lists of multi-cancer biomarkers are important in cancer development and represent the common signatures of malignancies of multiple cancer types. Pathway analysis revealed important tumorogenesis functional categories.

[1]  G. Tseng,et al.  Transcriptomic and genomic analysis of human hepatocellular carcinomas and hepatoblastomas , 2006, Hepatology.

[2]  G. Stark,et al.  Molecular analysis of a human interferon-inducible gene family. , 1991, European journal of biochemistry.

[3]  D. Pinkel,et al.  Regional copy number–independent deregulation of transcription in cancer , 2006, Nature Genetics.

[4]  P. Khatri,et al.  Global functional profiling of gene expression ? ? This work was funded in part by a Sun Microsystem , 2003 .

[5]  D. Hanahan,et al.  The Hallmarks of Cancer , 2000, Cell.

[6]  Roland Eils,et al.  Cross-platform analysis of cancer microarray data improves gene expression based classification of phenotypes , 2005, BMC Bioinformatics.

[7]  R. Foster,et al.  Structure and expression of the human metallothionein-IG gene. Differential promoter activity of two linked metallothionein-I genes in response to heavy metals. , 1988, The Journal of biological chemistry.

[8]  I. O. Ellis,et al.  Presence and possible significance of immunocytochemically demonstrable metallothionein over-expression in primary invasive ductal carcinoma of the breast , 2005, Virchows Archiv A.

[9]  E. Lander,et al.  Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[10]  R. Tibshirani,et al.  Diagnosis of multiple cancer types by shrunken centroids of gene expression , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Debashis Ghosh,et al.  Identification of GATA3 as a breast cancer prognostic marker by global gene expression meta-analysis. , 2005, Cancer research.

[12]  Daniel J. Park,et al.  A sequence-oriented comparison of gene expression measurements across different hybridization-based technologies , 2006, Nature Biotechnology.

[13]  S. Tsuji,et al.  Molecular cloning of human growth inhibitory factor cDNA and its down‐regulation in Alzheimer's disease. , 1992, The EMBO journal.

[14]  A. Jemal,et al.  Geographic Patterns of Prostate Cancer Mortality and Variations in Access to Medical Care in the United States , 2005, Cancer Epidemiology Biomarkers & Prevention.

[15]  Yingdong Zhao,et al.  Molecular Differentiation of High- and Moderate-Grade Human Prostate Cancer by cDNA Microarray Analysis , 2003, Diagnostic molecular pathology : the American journal of surgical pathology, part B.

[16]  E. Latulippe,et al.  Comprehensive gene expression analysis of prostate cancer reveals distinct transcriptional programs associated with metastatic disease. , 2002, Cancer research.

[17]  W. Sellers,et al.  Overexpression, Amplification, and Androgen Regulation of TPD52 in Prostate Cancer , 2004, Cancer Research.

[18]  T. Barrette,et al.  Meta-analysis of microarrays: interstudy validation of gene expression profiles reveals pathway dysregulation in prostate cancer. , 2002, Cancer research.

[19]  M. Becich,et al.  Gene expression alterations in prostate cancer predicting tumor aggression and preceding development of malignancy. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  D. Koller,et al.  A module map showing conditional activity of expression modules in cancer , 2004, Nature Genetics.

[21]  E. Lander,et al.  A molecular signature of metastasis in primary solid tumors , 2003, Nature Genetics.