title: Pathology-Driven Comprehensive Proteomic Profiling of the Prostate Cancer Tumor Microenvironment.
abstract: Prostate cancer is the second most common cancer in men worldwide. Gleason grading is an important predictor of prostate cancer outcomes and is influential in determining patient treatment options. Clinical decisions based on a Gleason score of 7 are difficult as the prognosis for individuals diagnosed with Gleason 4+3 cancer is much worse than for those diagnosed with Gleason 3+4 cancer. Laser capture microdissection (LCM) is a highly precise method to isolate specific cell populations or discrete microregions from tissues. This report undertook a detailed molecular characterization of the tumor microenvironment in prostate cancer to define the proteome in the epithelial and stromal regions from tumor foci of Gleason grades 3 and 4. Tissue regions of interest were isolated from several Gleason 3+3 and Gleason 4+4 tumors using telepathology to leverage specialized pathology expertise to support LCM. Over 2,000 proteins were identified following liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of all regions of interest. Statistical analysis revealed significant differences in protein expression (>100 proteins) between Gleason 3 and Gleason 4 regions-in both stromal and epithelial compartments. A subset of these proteins has had prior strong association with prostate cancer, thereby providing evidence for the authenticity of the approach. Finally, validation of these proteins by immunohistochemistry has been obtained using an independent cohort of prostate cancer tumor specimens.Implications:This unbiased strategy provides a strong foundation for the development of biomarker protein panels with significant diagnostic and prognostic potential.Mol Cancer Res; 15(3); 281-93. ©2017 AACR.
authors.affiliation: UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
authors.forename: Lisa
authors.initials: L
authors.lastname: Staunton
authors.affiliation: UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
authors.forename: Claire
authors.initials: C
authors.lastname: Tonry
authors.affiliation: Center for Molecular Oncologic Pathology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Rosina
authors.initials: R
authors.lastname: Lis
authors.affiliation: Center for Applied Proteomics, George Mason University, Fairfax, Virginia.
authors.forename: Virginia
authors.initials: V
authors.lastname: Espina
authors.affiliation: Center for Applied Proteomics, George Mason University, Fairfax, Virginia.
authors.forename: Lance
authors.initials: L
authors.lastname: Liotta
authors.affiliation: UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Inzitari
authors.affiliation: Center for Molecular Oncologic Pathology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Michaela
authors.initials: M
authors.lastname: Bowden
authors.affiliation: UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.|Department of Histopathology, St Vincent's University Hospital, Dublin, Ireland.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Fabre
authors.affiliation: Department of Histopathology, St. James's Hospital, Dublin, Ireland.
authors.forename: John
authors.initials: J
authors.lastname: O'Leary
authors.affiliation: Department of Histopathology, St. James's Hospital, Dublin, Ireland.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Finn
authors.affiliation: Center for Molecular Oncologic Pathology, Harvard Medical School, Boston, Massachusetts.|Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
authors.affiliation: UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland. stephen.pennington@ucd.ie.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Pennington
mesh_terms: D002853:Chromatography, Liquid; D066264:Datasets as Topic; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D040901:Proteomics / Q000379:methods; D059016:Tumor Microenvironment / Q000502:physiology*
chemical_list: D009363:Neoplasm Proteins