Antibodies to heat shock protein 90 in osteosarcoma patients correlate with response to neoadjuvant chemotherapy

Edelhauser

International Orthopaedics (SICOT)

et al. 2011

Purpose The purpose of this study was to investigate (a) whether pre-operative serum CRP is a predictor of survival in patients with high-grade osteosarcoma, (b) whether postoperative infection is a predictor of survival in these patients and (c) whether CRP is a predictor of postoperative infection, and especially deep prosthetic infection. Methods In this retrospective single-centre study, preoperative serum CRP levels in 79 patients (37 females, 42 males; average age, 18 years; mean follow-up, 46 months) undergoing resection of an osteosarcoma were correlated with clinical data and survival. Results The mean pre-operative serum CRP level of all 79 patients was 0.53 mg/dl (SD, 1.27 mg/dl). Patients dying of their underlying disease had significantly higher CRP levels compared to patients surviving throughout the follow-up period (1.09 mg/dl ± 2.02 mg/dl versus 0.32 mg/dl ± 0.75 mg/dl, respectively; p=0.015). CRP levels were significantly correlated with survival (Pearson's correlation coefficient= −0.25; p =0.026) and histological subtype (Pearson's correlation coefficient=−0.42; p<0.001), but not with sex, age, histological response, tumour size or metastatic disease. In uni-and multivariate survival analysis, age, response to chemotherapy and serum CRP were associated with disease-specific survival. Patients with a CRP level over 1 mg/dl had a significantly lower diseasespecific five-year survival of 36.7% compared to 73.8% in patients with normal CRP values (p=0.020). Infection was not correlated with disease-specific survival. Pre-operative serum CRP levels were not correlated with post-operative infection or deep prosthetic infection. Conclusions Pre-operative serum CRP seems to be an independent predictor of survival in patients with highgrade osteosarcoma. Further studies are needed to confirm these results on a large-scale basis.

Section: Discussionmentioning

confidence: 99%

Pre-operative serum C-reactive protein as independent prognostic factor for survival but not infection in patients with high-grade osteosarcoma

Edelhauser

International Orthopaedics (SICOT)

et al. 2011

“…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).…”

Section: Discussionmentioning

confidence: 99%

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

Nakajima¹

2010

Int J Oncol

Abstract. The Family with sequence similarity 107 (FAM107) possesses an N-terminal domain of unknown function (DUF1151) that is highly conserved beyond species. In human, FAM107A termed TU3A/DRR1 has been reported as a candidate tumor suppressor gene which expression is downregulated in several types of cancer, however no studies have investigated the other family protein, FAM107B. In the present study, we designated FAM107B as heat shockinducible tumor small protein (HITS) and studied its expression and functional properties in cancer. HITS is an 18-kDa nuclear protein expressed in a variety of tissues including stomach, colon, lung and lymphoid organs. In human gastric and colorectal cancers and a mouse model of colon cancer, its expression in tumor cells was much lower than normal epithelial cells, while expression pattern and intensity varied among different histological types of cancer. In functional analysis in vitro, forced expression of this protein suppresses the cellular responses to growth factors. Furthermore, HITS gene carries the promoter region providing heat shock transcription factor (HSF) binding sites and amplifying the transcription of HITS by heat shock or hyperthermia treatment both in vitro and in vivo. Thus HITS would be a potential tumor suppressor gene similar to TU3A containing heat responding elements, which contrasts with previously described oncogenic activities of other heat shock proteins such as HSP70 and HSP90.

“…The correlation of hsp90 autoantibodies and late stage ovarian cancer implies that it may have utilities as a novel prognostic biomarker for ovarian cancer. In osteosarcoma, hsp90 autoantibody positivity has been found to be associated with response to chemotherapy, whereas, its absence correlates with metastasis (Trieb et al, 2000). In contrast, Conroy et al (1998) reported that the presence of hsp90 autoantibodies indicated metastasis in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Identification of heat shock protein 90 and other proteins as tumour antigens by serological screening of an ovarian carcinoma expression library

et al. 2002

Serological screening of recombinant cDNA expression libraries has been widely used for the identification of tumour antigens in various cancer types. Identification of tumour antigens in ovarian cancer may facilitate the development of vaccine-based therapies and of disease biomarkers. The purpose of our investigation is to identify tumour antigens in ovarian cancer by using the serological analysis of recombinant cDNA expression libraries method. A recombinant ovarian carcinoma cDNA expression library was screened with ascites fluid, pooled from five ovarian cancer patients. Twelve tumour antigens encoded by known genes were isolated, including ribosomal protein S18, heat shock protein 90, JK-recombination signal binding protein, ribonucleoprotein H1, RAN binding protein 7, TG-interacting factor, eukaryotic translation initiation factor p40 subunit, human amyloid precursor protein-binding protein 1, ribosomal protein L8, CDC23, IQ motif containing GTPase activating protein 1, and ribosomal protein L3. Heat shock protein 90 was chosen for further investigation. The prevalence of hsp90 autoantibodies in ovarian cancer was determined with immunoassay. Sera from 22 normal females, 32 from ovarian cancer (22 stage III/IV, 10 stage I/II), 37 colorectal cancer, 13 breast cancer, 10 lung cancer, 20 benign gynaecologic diseases, and 10 benign breast lesions were screened. Seven (32%) stage III/IV ovarian cancer, 1 (10%) stage I/II ovarian cancer, 1 (3%) colorectal cancer, 1 (8%) breast cancer, and 1 (5%) benign gynaecologic disease sera were found to contain hsp90 autoantibodies. These data support the view that hsp90 autoantibodies are frequently found in late stage ovarian cancer. Hsp90 may, therefore, represent a novel biomarker for ovarian cancer and a candidate ovarian cancer vaccine target.