Delineation of prognostic biomarkers in prostate cancer

Prostate cancer is the most frequently diagnosed cancer in American men. Screening for prostate-specific antigen (PSA) has led to earlier detection of prostate cancer, but elevated serum PSA levels may be present in non-malignant conditions such as benign prostatic hyperlasia (BPH). Characterization of gene-expression profiles that molecularly distinguish prostatic neoplasms may identify genes involved in prostate carcinogenesis, elucidate clinical biomarkers, and lead to an improved classification of prostate cancer. Using microarrays of complementary DNA, we examined gene-expression profiles of more than 50 normal and neoplastic prostate specimens and three common prostate-cancer cell lines. Signature expression profiles of normal adjacent prostate (NAP), BPH, localized prostate cancer, and metastatic, hormone-refractory prostate cancer were determined. Here we establish many associations between genes and prostate cancer. We assessed two of these genes—hepsin, a transmembrane serine protease, and pim-1, a serine/threonine kinase—at the protein level using tissue microarrays consisting of over 700 clinically stratified prostate-cancer specimens. Expression of hepsin and pim-1 proteins was significantly correlated with measures of clinical outcome. Thus, the integration of cDNA microarray, high-density tissue microarray, and linked clinical and pathology data is a powerful approach to molecular profiling of human cancer.

[1]  R. P. Cowles.  Stimuli produced by light and by contact with solid walls as factors in the behavior of ophiuroids , 1910 .

[2]  David L. Pawson,et al.  X-ray Diffraction Studies of Echinoderm Plates , 1969, Science.

[3]  Euan N. K. Clarkson,et al.  Trilobite eyes and the optics of Des Cartes and Huygens , 1975, Nature.

[4]  Gordon Hendler,et al.  Brittlestar Color-Change and Phototaxis (Echinodermata: Ophiuroidea: Ophiocomidae). , 1984 .

[5]  J. Cobb,et al.  Comparative studies on receptor structure in the brittlestarOphiura ophiura , 1986, Journal of neurocytology.

[6]  J D Siegal,et al.  Enhanced expression of the c‐myc protooncogene in high‐grade human prostate cancers , 1988, The Prostate.

[7]  K. Kurachi,et al.  Hepsin, a cell membrane-associated protease. Characterization, tissue distribution, and gene localization. , 1991, The Journal of biological chemistry.

[8]  D. Gleason,et al.  Histologic grading of prostate cancer: a perspective. , 1992, Human pathology.

[9]  Stephen Mann,et al.  Synthesis of inorganic materials with complex form , 1996, Nature.

[10]  J. Kalbfleisch,et al.  Immunohistochemical detection of a fatty acid synthase (OA-519) as a predictor of progression of prostate cancer. , 1996, Human pathology.

[11]  J. Aizenberg,et al.  Imaging the irradiance distribution in the optical near field , 1997 .

[12]  S. Johnsen.  Identification and localization of a possible rhodopsin in the echinoderms Asterias forbesi (Asteroidea) and Ophioderma brevispinum (Ophiuroidea). , 1997, The Biological bulletin.

[13]  G. Whitesides,et al.  Soft Lithography. , 1998, Angewandte Chemie.

[14]  J. Kononen,et al.  Tissue microarrays for high-throughput molecular profiling of tumor specimens , 1998, Nature Medicine.

[15]  J. Mesirov,et al.  Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. , 1999, Science.

[16]  A W Partin,et al.  Natural history of progression after PSA elevation following radical prostatectomy. , 1999, JAMA.

[17]  Christopher Killian,et al.  Ultrastructural Localization of Proteins Involved in Sea Urchin Biomineralization , 1999, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[18]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[19]  G. Miller,et al.  Molecular genetics and epidemiology of prostate carcinoma. , 1999, Endocrine reviews.

[20]  N. Sampas,et al.  Molecular classification of cutaneous malignant melanoma by gene expression profiling , 2000, Nature.

[21]  J. Schalken,et al.  Cadherin switching in human prostate cancer progression. , 2000, Cancer research.

[22]  R. Narayanan,et al.  Microarray-based expression profiling in prostate tumors. , 2000, In vivo.

[23]  G. Horváth,et al.  Image formation by bifocal lenses in a trilobite eye? , 2000, Vision Research.

[24]  M. Rubin,et al.  Tissue microarray assessment of prostate cancer tumor proliferation in African- American and white men. , 2000, Journal of the National Cancer Institute.

[25]  G D Schuler,et al.  Molecular profiling of clinical tissue specimens: feasibility and applications. , 2000, The American journal of pathology.

[26]  Christian A. Rees,et al.  Molecular portraits of human breast tumours , 2000, Nature.

[27]  G D Schuler,et al.  Molecular profiling of clinical tissues specimens: feasibility and applications. , 2000, The Journal of molecular diagnostics : JMD.

[28]  Ash A. Alizadeh,et al.  Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling , 2000, Nature.

[29]  Emanuel Petricoin,et al.  Molecular profiling of human cancer , 2000, Nature Reviews Genetics.

[30]  K. Pienta,et al.  Rapid ("warm") autopsy study for procurement of metastatic prostate cancer. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[31]  T Visakorpi,et al.  Molecular genetics of prostate cancer. , 2001, Annals of medicine.

[32]  M. Barry.  Prostate-Specific–Antigen Testing for Early Diagnosis of Prostate Cancer , 2001 .

[33]  M. Byrne,et al.  Fine structure of the dorsal arm plate of Ophiocoma wendti: Evidence for a photoreceptor system (Echinodermata, Ophiuroidea) , 1987, Zoomorphology.