title: Prostate cancer: prognostic significance of the association of heterogeneous nuclear ribonucleoprotein K and androgen receptor expression.
abstract: The management of prostate cancer (PCa) remains challenging because to date, there has been no way to distinguish between indolent and aggressive tumors. Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is implicated in the network of mechanisms that control androgen receptor (AR) expression. We studied the expression of the two proteins in PCa to evaluate their prognostic potential and elucidate the hnRNP K function in PCa progression. HnRNP K and AR expression were analyzed immunohistochemically in 105 patients who had undergone radical prostatectomy. The association between the expression of hnRNP K and/or AR and PSA progression or death was evaluated by univariate and multivariate analyses. The expression of hnRNP K was also investigated in vitro using the BPH-1 cell line and two different LNCaP populations that recapitulate the progression of PCa towards a more aggressive disease. AR and hnRNP K were differentially expressed between cancer and normal prostate tissues. A strong association with a good prognosis was evident in PCa exhibiting high percentage of AR-positive cells (>75%) (p≤0.005) and more interestingly, the combination of high AR and low cytoplasmic hnRNP K expression emerged as the most significant independent prognostic marker for PSA failure-free survival, in a multivariate analysis (p≤0.001). In vitro, a higher expression of hnRNP K and pERK was associated with higher PSA levels, suggesting a relationship between hnRNP K phosphorylation and AR-regulated genes. These results indicate that the interaction between the AR and hnRNP K has an important role in the progression of PCa. Changes of the expression of the two proteins are strongly associated with the clinical outcome and may be a potential prognostic marker.
authors.affiliation: IRCCS San Martino University Hospital, IST National Cancer Research Institute, I-16132 Genova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Barboro
authors.affiliation: IRCCS San Martino University Hospital, IST National Cancer Research Institute, I-16132 Genova, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Salvi
authors.affiliation: Academic Department of Medical Oncology and IRCCS San Martino University Hospital, IST National Cancer Research Institute, I-16132 Genova, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rubagotti
authors.affiliation: IRCCS San Martino University Hospital, IST National Cancer Research Institute, I-16132 Genova, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Boccardo
authors.affiliation: IRCCS San Martino University Hospital, IST National Cancer Research Institute, I-16132 Genova, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Spina
authors.affiliation: IRCCS San Martino University Hospital, IST National Cancer Research Institute, I-16132 Genova, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Truini
authors.affiliation: Academic Department of Surgical Sciences, School of Medicine and IRCCS San Martino University Hospital, IST National Cancer Research Institute, I-16132 Genova, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Carmignani
authors.affiliation: IRCCS San Martino University Hospital, IST National Cancer Research Institute, I-16132 Genova, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Introini
authors.affiliation: IRCCS San Martino University Hospital, IST National Cancer Research Institute, I-16132 Genova, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Ferrari
authors.affiliation: Academic Department of Medical Oncology and IRCCS San Martino University Hospital, IST National Cancer Research Institute, I-16132 Genova, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Boccardo
authors.affiliation: IRCCS San Martino University Hospital, IST National Cancer Research Institute, I-16132 Genova, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Balbi
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D010766:Phosphorylation; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D011944:Receptors, Androgen / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D011944:Receptors, Androgen; D017430:Prostate-Specific Antigen