Heat shock proteins 27, 60 and 70 as prognostic markers of prostate cancer. APMIS

Department of Oncology, Karolinska Institutet, Stockholm, Sweden.
Apmis (Impact Factor: 2.04). 10/2008; 116(10):888-95. DOI: 10.1111/j.1600-0463.2008.01051.x
Source: PubMed


Heat shock proteins (HSPs) protect cells against stress-associated injury and are overexpressed in several malignant tumors. We aimed to investigate their value as prognostic markers in prostate cancer. A tissue microarray (TMA) was constructed of 289 prostate cancers from radical prostatectomy (RP) specimens with median follow-up of 48.9 months. Slides were immunostained for HSP27, HSP60 and HSP70. Intensity and extent of immunoreactivity (IR) and their product (IRp) was evaluated by two observers. The IRp of HSP27 and HSP60, but not of HSP70, significantly predicted biochemical recurrence (p=0.014, 0.034 and 0.160, respectively). Recurrence-free survival in patients with strong HSP27 and HSP60 staining was shorter than in those with weak expression (p=0.019 and 0.001, respectively). IRp of HSP27 and HSP60 correlated with Gleason score (p<0.01). HSP60 was an independent predictor of biochemical recurrence in multivariate analysis, including extraprostatic extension, margin status, seminal vesicle invasion and Gleason score. Weighted kappa for interobserver agreement of HSP27, HSP60 and HSP70 IR was 0.613-0.823 for intensity and 0.584-0.719 for IRp, but only 0.036-0.244 for extent, raising the question whether staining extent should be estimated on TMA. We conclude that HSP27 and HSP60 are predictors of biochemical recurrence after RP.

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    • "Among those antiapoptotic factors, bcl-2 [6], clusterin [7], heat shock prostein 27 (Hsp27) [8, 9], cellular-FLICE inhibitory protein (c-FLIP) [10], and GRP78 [11] have been widely reported. Overexpression of these factors could be induced by androgen deprivation therapy (ADT), chemotherapy, or other extreme stresses. "
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    ABSTRACT: We evaluated effect of dual gene silencing of Hsp27 and c-FLIP in doxazosin-induced apoptosis of PC-3 cell. After transfection using Hsp27 and c-FLIP siRNA mixture (dual silencing), doxazosin treatment was done at the concentrations of 1, 10, and 25 μ M. We checked apoptosis of PC-3 cells with and TUNEL staining. We also checked interaction between Hsp27 and C-FLIP in the process of apoptosis inhibition. Spontaneous apoptotic index was 5% under single gene silencing of Hsp27 and c-FLIP and 7% under dual silencing of Hsp27 and c-FLIP. When doxazosin treatment was added, apoptotic indices increased in a dose-dependent manner (1, 10, and 25 μ M): nonsilencing 10, 27, and 52%; Hsp27-silencing: 14, 35, and 68%; c-FLIP silencing: 21, 46, and 78%; dual silencing: 38, 76, and 92%. While c-FLIP gene expression decreased in Hsp27- silenced cells, Hsp27 gene expression showed markedly decreased pattern in the cells of c-FLIP silencing. The knockout of c-FLIP and Hsp27 genes together enhances apoptosis even under 1 μ M, rather than low concentration, of doxazosin in PC-3 cells. This finding suggests a new strategy of multiple knockout of antiapoptotic and survival factors in the treatment of late-stage prostate cancer refractory to conventional therapy.
    The Scientific World Journal 06/2013; 2013(1):174392. DOI:10.1155/2013/174392 · 1.73 Impact Factor
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    • "HSPD1 also interacts with Hsp70, survivin and p53 to participate in apoptosis. Recently, HSPD1 was associated with carcinogenesis, specifically tumor cell survival and proliferation, in different types of cancer [41], [42], [43]. This is the first report to suggest HSPD1 may be a potential biomarker of CC. "
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    ABSTRACT: Cholangiocarcinoma (CC) is an intractable cancer, arising from biliary epithelial cells, which has a poor prognosis and is increasing in incidence. Early diagnosis of CC is essential as surgical resection remains the only effective therapy. The purpose of this study was to identify improved biomarkers to facilitate early diagnosis and prognostication in CC. A comparative expression profile of human bile samples from patients with cholangitis and CC was constructed using a classic 2D/MS/MS strategy and the expression of selected proteins was confirmed by Western blotting. Immunohistochemistry was performed to determine the expression levels of selected candidate biomarkers in CC and matched normal tissues. Finally, spermatogenesis associated 20 (SSP411; also named SPATA20) was quantified in serum samples using an ELISA. We identified 97 differentially expressed protein spots, corresponding to 49 different genes, of which 38 were upregulated in bile from CC patients. Western blotting confirmed that phosphoglycerate mutase 1 (brain) (PGAM-1), protein disulfide isomerase family A, member 3 (PDIA3), heat shock 60 kDa protein 1 (chaperonin) (HSPD1) and SSP411 were significantly upregulated in individual bile samples from CC patients. Immunohistochemistry demonstrated these proteins were also overexpressed in CC, relative to normal tissues. SSP411 displayed value as a potential serum diagnostic biomarker for CC, with a sensitivity of 90.0% and specificity of 83.3% at a cutoff value of 0.63. We successfully constructed a proteomic profile of CC bile proteins, providing a valuable pool novel of candidate biomarkers. SSP411 has potential as a biomarker for the diagnosis of CC.
    PLoS ONE 10/2012; 7(10):e47476. DOI:10.1371/journal.pone.0047476 · 3.23 Impact Factor
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    • "In our work from MD lymphocytes in vivo, BCL2 protein was unchanged suggesting that any BCL2 functional-deregulation may occur prior to the CD30lo to CD30hi transition in the lymphoma environment. HSP70 inhibits both the intrinsic and the extrinsic PCD mechanisms and is frequently increased in malignant tumors [47-50], Meq also co-localizes with HSP70 in the nucleus [49] where HSP70 mediates Meq’s interaction with TP53 and CDK2 [49]. In agreement, we found HSP70 protein was increased and was 100% nuclear. "
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    BMC Systems Biology 09/2012; 6(1):123. DOI:10.1186/1752-0509-6-123 · 2.44 Impact Factor
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