Androgens play a central role in prostate cancer pathogenesis, and hence most of the patients respond to androgen deprivation therapies. However, patients tend to relapse with aggressive prostate cancer, which has been termed as hormone refractory. To identify the proteins that mediate progression to the hormone-refractory state, we used protein-chip technology for mass profiling of patients' sera. This study included 16 patients with metastatic hormone-refractory prostate cancer who were initially treated with androgen deprivation therapy. Serum samples were collected from each patient at five time points: point A, pre-treatment; point B, at the nadir of the prostate-specific antigen (PSA) level; point C, PSA failure; point D, the early hormone-refractory phase; and point E, the late hormone-refractory phase. Using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, we performed protein mass profiling of the patients' sera and identified a 6 640-Da peak that increased with disease progression. Target proteins were partially purified, and by amino acid sequencing the peak was identified as a fragment of apolipoprotein C-I (ApoC-I). Serum ApoC-I protein levels increased with disease progression. On immunohistochemical analysis, the ApoC-I protein was found localized to the cytoplasm of the hormone-refractory cancer cells. In this study, we showed an increase in serum ApoC-I protein levels in prostate cancer patients during their progression to the hormone-refractory state, which suggests that ApoC-I protein is related to progression of prostate cancer. However, as the exact role of ApoC-I in prostate cancer pathogenesis is unclear, further research is required.
Aged ; Amino Acid Sequence ; Antineoplastic Agents, Hormonal ; therapeutic use ; Apolipoprotein C-I ; analysis ; blood ; isolation & purification ; Blotting, Western ; Cell Line ; Disease Progression ; Drug Resistance, Neoplasm ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Molecular Sequence Data ; Prognosis ; Prostatic Neoplasms ; drug therapy ; metabolism ; Protein Array Analysis ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Results: In the early phase after surgery, 71% and 43% of the participants were nonindependent ambulators at 1W and 2W, respectively. Histopathology indicated that patients with solid tumors (ependymoma, astrocytoma, or lipoma) showed significantly lower indices at 1W and 2W than those with vascular tumors (hemangioblastoma or cavernous hemangioma). Regarding tumor location, thoracic cases exhibited poorer lower-limb function at 1W and 2W and poorer walking ability at 2W than cervical cases. According to the receiver operating characteristic (ROC) analysis, 2 WISCI II points at 2W had the highest sensitivity (100%) and specificity (92.2%) in predicting the level of walking independence at 1 year postoperatively (the area under the ROC curve was 0.99 (95% confidence interval, 0.93–1.00). Conclusions The higher the lower-limb function scores in the early phase, the better the improvement in walking ability is predicted 1 year after ISCT resection.