Hsp-27 expression at diagnosis predicts poor clinical outcome in prostate cancer independent of ETS-gene rearrangement

Abstract

Background: This study was performed to test the hypothesis that expression of small heat shock protein Hsp-27 is, at diagnosis, a reliable predictive biomarker of clinically aggressive prostate cancer. Methods: A panel of tissue microarrays constructed from a well-characterised cohort of 553 men with conservatively managed prostate cancer was stained immunohistochemically to detect Hsp-27 protein. Hsp-27 expression was compared with a series of pathological and clinical parameters, including outcome. Results: Hsp-27 staining was indicative of higher Gleason score ( P <0.001). In tissue cores having a Gleason score >7, the presence of Hsp-27 retained its power to independently predict poor clinical outcome ( P <0.002). Higher levels of Hsp-27 staining were almost entirely restricted to cancers lacking ERG rearrangements ( χ 2 trend=31.4, P <0.001), although this distribution did not have prognostic significance. Interpretation: This study has confirmed that, in prostate cancers managed conservatively over a period of more than 15 years, expression of Hsp-27 is an accurate and independent predictive biomarker of aggressive disease with poor clinical outcome ( P <0.001). These findings suggest that apoptotic and cell-migration pathways modulated by Hsp-27 may contain targets susceptible to the development of biologically appropriate chemotherapeutic agents that are likely to prove effective in treating aggressive prostate cancers.

Induction of HITS, a newly identified family with sequence similarity 107 protein (FAM107B), in cancer cells by heat shock stimulation

“…In breast cancer, overexpression of HSP70 and HSP90 correlates with poor prognosis (37,38). Overexpression of HSPs also contributes to drug resistance and a poor response to combination chemotherapy (39)(40)(41)(42). HSF1 is the master regulator of the heat shock response in eukaryotes, a highly conserved protective mechanism against heat stimulation (43).…”

Clinical significance of HSP27 expression in colorectal cancer

“…in contrast, its aberrant expression has been reported in a variety of human cancers, including breast (9), ovarian (10), gastric (11), prostate (12), endometrial (13), liver (14), bladder (15) and leukemia (16). Furthermore, elevated HSP27 levels in breast, ovarian, gastric, and prostate cancer is associated with aggressive growth and resistance to chemotherapy or radiotherapy, and hence with a poor prognosis (9)(10)(11)(12). There is considerable evidence indicating that elevated expression of HSP27 in tumor cells enhances their tumorigenicity (17).…”

Expression Profi ling of Hspb1 and Tp53 Genes through RT-qPCR in Different Cancer Types of Canis familiaris

“…Expression of Hsp27 is considered to be reliable predictive biomarkers of aggressive human cancers (29)(30)(31)(32). However, few reports are available regarding their role in animal cancers.…”