Evaluation of PSA-age volume score in predicting prostate cancer in Chinese population.

This study was performed to evaluate prostate-specific antigen-age volume (PSA-AV) scores in predicting prostate cancer (PCa) in a Chinese biopsy population. A total of 2355 men who underwent initial prostate biopsy from January 2006 to November 2015 in Huashan Hospital were recruited in the current study. The PSA-AV scores were calculated and assessed together with PSA and PSA density (PSAD) retrospectively. Among 2133 patients included in the analysis, 947 (44.4%) were diagnosed with PCa. The mean age, PSA, and positive rates of digital rectal examination result and transrectal ultrasound result were statistically higher in men diagnosed with PCa (all P < 0.05). The values of area under the receiver operating characteristic curves (AUCs) of PSAD and PSA-AV were 0.864 and 0.851, respectively, in predicting PCa in the entire population, both performed better than PSA (AUC = 0.805; P < 0.05). The superiority of PSAD and PSA-AV was more obvious in subgroup with PSA ranging from 2.0 ng ml-1 to 20.0 ng ml-1. A PSA-AV score of 400 had a sensitivity and specificity of 93.7% and 40.0%, respectively. In conclusion, the PSA-AV score performed equally with PSAD and was better than PSA in predicting PCa. This indicated that PSA-AV score could be a useful tool for predicting PCa in Chinese population.

miR-181 regulation of BAX controls cisplatin sensitivity of prostate cancer cells.

Prostate cancer is one of the most common male malignancies and remains the second leading cause for cancer-specific mortalities in men. Cisplatin is commonly used as a chemotherapeutic agent against advanced cancers, and is now used in metastatic prostate cancers. Cisplatin exerts its cytotoxic effects by cross-linking genomic DNA (gDNA) which induces DNA damage on rapidly dividing cancer cells. However, cisplatin leads to systemic side effects and some patients never respond. Our previous report demonstrated an oncogenic role of miR-181a in human prostate cancer. In this study, we investigate the mechanistic potential of miR-181a in regulating cisplatin sensitivity in this context. We report that cisplatin treatment significantly enhanced miR-181a expression and that exogenous overexpression of miR-181a decreased sensitivity of prostate cancer cells to cisplatin. Additionally, we observed that cisplatin-resistant prostate cancer cells harbored high levels of miR-181a expression. Mechanistically, we demonstrate the pro-apoptotic protein, BAX, is typically enhanced by cisplatin treatment but its suppression promoted resistance. Here we demonstrate miR-181a regulation of BAX was mediated through a complimentary interaction with the 3'UTR of the BAX transcript. We subsequently show that BAX expression restored cisplatin sensitivity in miR-181a overexpressing prostate cancer cells. In parallel, we demonstrate inhibition of miR-181a restored BAX expression as well as cisplatin sensitivity in resistant cells. This study suggests that miR-181a is a potential therapeutic target for prostate cancers that are resistant to cisplatin.

The Huashan risk calculators performed better in prediction of prostate cancer in Chinese population: a training study followed by a validation study.

The performances of the Prostate Cancer Prevention Trial (PCPT) risk calculator and other risk calculators for prostate cancer (PCa) prediction in Chinese populations were poorly understood. We performed this study to build risk calculators (Huashan risk calculators) based on Chinese population and validated the performance of prostate-specific antigen (PSA), PCPT risk calculator, and Huashan risk calculators in a validation cohort. We built Huashan risk calculators based on data from 1059 men who underwent initial prostate biopsy from January 2006 to December 2010 in a training cohort. Then, we validated the performance of PSA, PCPT risk calculator, and Huashan risk calculators in an observational validation study from January 2011 to December 2014. All necessary clinical information were collected before the biopsy. The results showed that Huashan risk calculators 1 and 2 outperformed the PCPT risk calculator for predicting PCa in both entire training cohort and stratified population (with PSA from 2.0 ng ml-1 to 20.0 ng m). In the validation study, Huashan risk calculator 1 still outperformed the PCPT risk calculator in the entire validation cohort (0.849 vs 0.779 in area under the receiver operating characteristic curve [AUC] and stratified population. A considerable reduction of unnecessary biopsies (approximately 30%) was also observed when the Huashan risk calculators were used. Thus, we believe that the Huashan risk calculators (especially Huashan risk calculator 1) may have added value for predicting PCa in Chinese population. However, these results still needed further evaluation in larger populations.

Farnesoid X receptor inhibits LNcaP cell proliferation via the upregulation of PTEN.

Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. In the present study, the activation of the farnesoid X receptor (FXR), a member of the nuclear receptor superfamily, was demonstrated to inhibit cell proliferation in LNcaP cells. Using clinical samples, mRNA and protein levels of FXR were found to be significantly decreased by quantitative PCR and western blot analysis in prostate cancer tissues. In vitro studies identified further that activation or overexpression of FXR suppressed prostate cancer cell proliferation as measured by BrdU incorporation assays. At the molecular level, the results further revealed that the expression of the tumor suppressor gene, PTEN, was upregulated by FXR activation. Therefore, the observations indicated that FXR functions as a tumor suppressor in prostate cancer, which may provide a novel method for molecular targeting cancer treatment.

microRNA-181 promotes prostate cancer cell proliferation by regulating DAX-1 expression.

microRNAs (miRNAs) are a class of short noncoding RNA molecules that have a critical role in the initiation and progression of types of human cancer, including prostate cancer. In the present study, the expression of miR-181 in prostate cancer tissues was evaluated and was demonstrated to be significantly upregulated in prostate cancer tissues compared with that in adjacent normal tissues. The results of in vitro MTT and BrdU incorporation assays, as well as cell-cycle analysis, indicated that miR-181 overexpression markedly promoted the proliferation of LNCaP cells. Furthermore, miR-181 overexpression was found to promote the progression of LNCaP tumor growth in nude mice. Mechanistic studies demonstrated that dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 (DAX-1), a negative regulator of androgen receptor in prostate cancer, was inhibited by miR-181 overexpression. Therefore, the results from the present study suggest that miR-181 functions as a growth-suppressive miRNA during prostate cancer development.

Prostate-specific antigen kinetics under androgen deprivation therapy and prostate cancer prognosis.

OBJECTIVES: To compare the difference in characteristics of post-treatment prostate-specific antigen (PSA) kinetics among respective patients and their influence on disease prognosis. METHODS: A cohort of totally 332 eligible patients with histologically confirmed and hormonally naïve prostate cancer, identified from the patients' database of Huashan Hospital, all received combined androgen deprivation therapy including bilateral orchiectomy or luteinizing hormone-releasing hormone antagonists with the oral administration of flutamide 250 mg t.i.d. All patients had their serum PSA level tested at least every 3 months in the first 2 years and at least once a half year from the third year on. PSA nadir, time to PSA nadir (TTPN), PSA normalization (<4 ng/ml), undetectable PSA level (<0.2 ng/ml), biochemical failure, overall survival and cancer-specific survival were analyzed. RESULTS: PSA normalization, TTPN, and reaching the undetectable PSA level perhaps were the independent risk factors for predicting the three types of prognosis. Probably the best cut-off of PSA nadir was 0.2 ng/ml (sensitivity 65.7%, specificity 80.6%) and the best cut-off of TTPN was 10 months (sensitivity 71.6%, specificity 63.9%). CONCLUSIONS: These results implied that a lower level of PSA nadir and longer TTPN can predict a better disease prognosis.