title: hCAP-D3 expression marks a prostate cancer subtype with favorable clinical behavior and androgen signaling signature.
abstract: Growing evidence suggests that only a fraction of prostate cancers detected clinically are potentially lethal. An important clinical issue is identifying men with indolent cancer who might be spared aggressive therapies with associated morbidities. Previously, using microarray analysis we defined 3 molecular subtypes of prostate cancer with different gene-expression patterns. One, subtype-1, displayed features consistent with more indolent behavior, where an immunohistochemical marker (AZGP1) for subtype-1 predicted favorable outcome after radical prostatectomy. Here we characterize a second candidate tissue biomarker, hCAP-D3, expressed in subtype-1 prostate tumors. hCAP-D3 expression, assayed by RNA in situ hybridization on a tissue microarray comprising 225 cases, was associated with decreased tumor recurrence after radical prostatectomy (P=0.004), independent of pathologic tumor stage, Gleason grade, and preoperative prostate-specific antigen levels. Simultaneous assessment of hCAP-D3 and AZGP1 expression in this tumor set improved outcome prediction. We have previously demonstrated that hCAP-D3 is induced by androgen in prostate cells. Extending this finding, Gene Set Enrichment Analysis revealed enrichment of androgen-responsive genes in subtype-1 tumors (P=0.019). Our findings identify hCAP-D3 as a new biomarker for subtype-1 tumors that improves prognostication, and reveal androgen signaling as an important biologic feature of this potentially clinically favorable molecular subtype.
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA 94305-51, USA.
authors.forename: Jacques
authors.initials: J
authors.lastname: Lapointe
authors.forename: Sameer
authors.initials: S
authors.lastname: Malhotra
authors.forename: John P
authors.initials: JP
authors.lastname: Higgins
authors.forename: Eric
authors.initials: E
authors.lastname: Bair
authors.forename: Maxwell
authors.initials: M
authors.lastname: Thompson
authors.forename: Keyan
authors.initials: K
authors.lastname: Salari
authors.forename: Craig P
authors.initials: CP
authors.lastname: Giacomini
authors.forename: Michelle
authors.initials: M
authors.lastname: Ferrari
authors.forename: Kelli
authors.initials: K
authors.lastname: Montgomery
authors.forename: Robert
authors.initials: R
authors.lastname: Tibshirani
authors.forename: Matt
authors.initials: M
authors.lastname: van de Rijn
authors.forename: James D
authors.initials: JD
authors.lastname: Brooks
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Pollack
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D054392:Adipokines; D000728:Androgens / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D046912:Multiprotein Complexes / Q000235:genetics* / Q000378:metabolism; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D012334:RNA, Neoplasm / Q000032:analysis; D015398:Signal Transduction; D015996:Survival Rate; D046888:Tissue Array Analysis; D000090203:Zn-Alpha-2-Glycoprotein
chemical_list: D000251:Adenosine Triphosphatases; D054392:Adipokines; D000728:Androgens; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006023:Glycoproteins; D046912:Multiprotein Complexes; D012334:RNA, Neoplasm; C488891:AZGP1 protein, human; D000090203:Zn-Alpha-2-Glycoprotein; C108312:condensin complexes