ABSTRACT
In recent years, saliva samples have attracted attention as specimens, which may be used for cancer diagnosis. Prostate-specific antigen (PSA) is the most useful tumor marker for prostate adenocarcinoma (PA). We examined whether there is an association between saliva PSA and serum PSA in patients with PA using enzyme-linked immunosorbent assay. Human subjects were classified into two groups: a low-serum PSA concentration group (n = 20) (<2.5 ng/mL) and a high-serum PSA concentration group with high risk of recurrence or metastasis (n = 11) (≤2.5 ng/mL). There were significant differences in saliva PSA concentration between these groups (p < 0.05). Saliva PSA concentration correlated very well with serum PSA concentration in the high-serum PSA concentration group (γ = 0.910, p < 0.001) using Spearman's rank test, but no correlation in the low-serum PSA concentration group. This result suggests that saliva PSA is associated with blood PSA in patients with recurrent or metastatic PA and may, therefore, be a useful PA biomarker.
Subject(s)
Adenocarcinoma/diagnosis , Biomarkers, Tumor/blood , Prostate-Specific Antigen/blood , Prostate/metabolism , Prostatic Neoplasms/diagnosis , Saliva/chemistry , Submandibular Gland/chemistry , Adenocarcinoma/blood , Adenocarcinoma/pathology , Aged , Aged, 80 and over , Animals , Enzyme-Linked Immunosorbent Assay , Humans , Male , Mice , Mice, SCID , Middle Aged , Prostate/pathology , Prostate-Specific Antigen/biosynthesis , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , RNA, Messenger/analysis , RNA, Messenger/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction , Submandibular Gland/metabolism , Xenograft Model Antitumor AssaysABSTRACT
BACKGROUND: Androgen receptor (AR) transcription is modulated by several cofactors such as AR associated proteins (ARA) including ARA70, ARA54, and ARA55. ARA55 increases AR transcription and alters ligand specificity. We hypothesized that ARA55 might play an important role in prostate cancer development or progression. We evaluated the messenger RNA (mRNA) expression of ARA55 in prostate cancer tissues, and analyzed the relation between ARA55 expression and clinical characteristics. METHODS: A total of 30 prostate cancer specimens (20 previously untreated prostate cancers and 10 recurrent, hormone-refractory prostate cancers (HRPC)) and 5 benign prostatic hypertrophy (BPH) tissue samples were examined. mRNA expression of ARA55 and AR were analyzed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) using real time PCR. RESULTS: ARA55 expression was identified in all tissue samples of previously untreated prostate cancer, HRPC and BPH. ARA55 expression level in HRPC specimens was significantly lower than that in previously untreated prostate cancer (P = 0.02) or BPH (P = 0.005) samples using quantitative PCR. On the other hand, higher ARA55 expression was associated with shorter recurrence-free survival (P = 0.02) and overall survival (P = 0.01) in HRPC patients. AR expression was also revealed in all specimens of both prostate cancer and BPH. AR expression level in HRPC samples was significantly higher than that in previously untreated prostate cancer (P = 0.001) and BPH (P = 0.01) samples. CONCLUSIONS: ARA55 may be associated with prostate cancer development and progression. ARA55 expression level in HRPC specimens was significantly lower than that in previously untreated prostate cancer or BPH specimens. On the contrary, our results suggested that a higher ARA55 expression level may result in unfavorable recurrence-free survival and overall survival in HRPC patients. The role of ARA55 may differ between prostate cancer development and the process of progression to a hormone-refractory state. These data not only help to understand the molecular mechanism of prostate cancer development or recurrence, but may also lead to a therapeutic strategy for recurrent prostate cancer that is refractory to hormonal treatment.
