Xiaolei Shi

Prostate cancer in Asia: A collaborative report

The incidence of prostate cancer (PCa) within Asian population used to be much lower than in the Western population; however, in recent years the incidence and mortality rate of PCa in some Asian countries have grown rapidly. This collaborative report summarized the latest epidemiology information, risk factors, and racial differences in PCa diagnosis, current status and new trends in surgery management and novel agents for castration-resistant prostate cancer. We believe such information would be helpful in clinical decision making for urologists and oncologists, health-care ministries and medical researchers.

A novel urinary long non-coding RNA transcript improves diagnostic accuracy in patients undergoing prostate biopsy

Long non‐coding RNA (LncRNA) PCA3 has been a well‐established urine biomarker for the detection of prostate cancer (PCa). Our previous study showed a novel LncRNA FR0348383 is up‐regulated in over 70% of PCa compared with matched benign tissues. The aim of this study was to evaluate the diagnostic value of urinary FR0348383 for men undergoing prostate biopsy due to elevated PSA (PSA > 4.0 ng/ml) and/or abnormal digital rectal examination (DRE).

A feed-forward regulatory loop between androgen receptor and PlncRNA-1 promotes prostate cancer progression

We previously reported that PlncRNA-1, a long non-coding RNA that is up-regulated in prostate cancer (PCa), affects the proliferation and apoptosis of PCa cells. However, the molecular mechanisms underlying these effects remain largely unknown. In this study, we demonstrated that long non-coding RNA PlncRNA-1, whose expression is promoted by Androgen Receptor (AR), protects AR from microRNA-mediated suppression in PCa cells. PlncRNA-1 knockdown resulted in the up-regulation of a series of AR-targeting microRNAs, among which miR-34c and miR-297 were found to regulate both AR and PlncRNA-1 expression at the post-transcriptional level. Functional analysis revealed that miR-34c and miR-297 overexpression down-regulated AR expression and inhibited the expression of downstream AR targets and that PlncRNA-1 overexpression rescued these effects. The association of PlncRNA-1 with tumor progression was also evaluated in mouse xenograft models, PCa tissues (16 paired samples), and blood samples (35 biopsy-negative and 37 biopsy-positive). Together, the data generated in this study indicate that PlncRNA-1 sponges AR-targeting microRNAs to protect AR from microRNA-mediated down-regulation and that these events form a regulatory feed-forward loop in the development of PCa. These findings suggest that PlncRNA-1 might potentially serve as a novel biomarker in PCa and that PlncRNA-1 might warrant further investigation to determine its potential role as a promising therapeutic target in PCa.

Clinical utility of a novel urine-based gene fusion TTTY15-USP9Y in predicting prostate biopsy outcome.

OBJECTIVE In recent years, great effort has been made to explore new biomarkers for early detection of prostate cancer. Our previous study has demonstrated the high prevalence of TTTY15-USP9Y in prostate cancer samples from a Chinese population. Our aim was to evaluate the clinical utility of TTTY15-USP9Y in predicting the prostate biopsy outcome. MATERIALS AND METHODS We retrospectively examined the expression of TTTY15-USP9Y in 226 qualified urine sediment samples. Total RNA was extracted from the urine sediment by using TRIzol reagent, and complementary DNA was synthesized using TransPlex Complete Whole Transcriptome Amplification Kit (WTA2). Real-time quantitative polymerase chain reaction was performed to evaluate the expression of TTTY15-USP9Y and the prostate cancer-specific antigen (PSA) level. The TTTY15-USP9Y score was calculated as 2(Ct(PSA)-Ct(TTTY15-USP9Y))× 1,000. RESULTS The TTTY15-USP9Y score was statistically significantly higher in men with positive biopsy outcome than in men with negative biopsy outcome (P<0.001). The area under the curve was 0.828 for the TTTY15-USP9Y score in the entire patient cohort. The TTTY15-USP9Y score׳s cutoff of 90.28 provided the optimal balance between sensitivity (84.0%) and specificity (77.5%). The combination of PSA level and the TTTY15-USP9Y score significantly improved the diagnostic performance of PSA level (P = 0.001). The TTTY15-USP9Y score alone was superior to PSA level, percent free PSA, and PSA density (serum PSA/prostate volume) in the subgroup of clinical interest (PSA level: 4-10ng/ml, gray zone). Univariable and multivariable logistic analyses indicated that TTTY15-USP9Y score, PSA level, age, and prostate volume were independent predictors of PCa. Adding the TTTY15-USP9Y score in the clinical base model (PSA level, age, and prostate volume) could bring a higher net benefit and reduce more unnecessary biopsies in the defined range of interest (10%-40% threshold probability). CONCLUSION In conclusion, our study explored the potential utility of measuring the TTTY15-USP9Y score in post-digital rectal examination urine samples to predict biopsy outcome and provided the basis for the utility of this novel gene fusion in multicenter and large cohort studies.

Indirect comparison between abiraterone acetate and enzalutamide for the treatment of metastatic castration-resistant prostate cancer: a systematic review

This study was designed to evaluate the efficacy, tolerability, and sequential administration of abiraterone acetate (AA) and enzalutamide (Enz) for metastatic castration-resistant prostate cancer (mCRPC). A literature search was performed with PubMed, Embase, and Web of Science databases to identify relevant studies. Reviewed literature included published phase III trials of AA or Enz in mCRPC and studies regarding their sequential administration. Given the difference in control arms in AA (active comparator) and Enz (true placebo) randomized phase III studies, indirect comparisons between AA and Enz in mCRPC showed no statistically significant difference in overall survival in prechemotherapy and postchemotherapy settings (HR: 0.90, 95% CI, 0.73-1.11; HR: 0.85, 95% CI, 0.68-1.07). Compared with AA, Enz may better outperform control arms in treating mCRPC both before and after chemotherapy regarding secondary endpoints based on indirect comparisons: time to prostate-specific antigen (PSA) progression (HR: 0.34, 95% CI, 0.28-0.42; HR: 0.40, 95% CI, 0.30-0.53), radiographic progression-free survival (HR: 0.37, 95% CI, 0.28-0.48; HR: 0.61, 95% CI, 0.50-0.74), and PSA response rate (OR: 18.29, 95% CI, 11.20-29.88; OR: 10.69, 95% CI, 3.92-29.20). With regard to the effectiveness of Enz following AA or AA following Enz, recent retrospective case series reported overall survival and secondary endpoints for patients with mCRPC progression after chemotherapy. However, confirmatory head-to-head trials are necessary to determine the optimal sequencing of these agents.

Prostate cancer antigen 3 moderately improves diagnostic accuracy in Chinese patients undergoing first prostate biopsy

Prostate cancer antigen 3 (PCA3) is a biomarker for diagnosing prostate cancer (PCa) identified in the Caucasian population. We evaluated the effectiveness of urinary PCA3 in predicting the biopsy result in 500 men undergoing initial prostate biopsy. The predictive power of the PCA3 score was evaluated by the area under receiver operating characteristic (ROC) curve (AUC) and by decision curve analysis. PCA3 score sufficed to discriminate positive from negative prostate biopsy results but was not correlated with the aggressiveness of PCa. The ROC analysis showed a higher AUC for the PCA3 score than %fPSA (0.750 vs 0.622, P = 0.046) in patients with a PSA of 4.0-10.0 ng ml−1 , but the PCA3-based model is not significantly better than the base model. Decision curve analysis indicates the PCA3-based model was superior to the base model with a higher net benefit for almost all threshold probabilities, especially the threshold probabilities of 25%-40% in patients with a PSA of 4.0-10.0 ng ml−1 . However, the AUC of the PCA3 score (0.712) is not superior to %fPSA (0.698) or PSAD (0.773) in patients with a PSA >10.0 ng ml−1 . Our results confirmed that the RT-PCR-based PCA3 test moderately improved diagnostic accuracy in Chinese patients undergoing first prostate biopsy with a PSA of 4.0-10.0 ng ml−1 .

Renal function changes after percutaneous nephrolithotomy in patients with renal calculi with a solitary kidney compared to bilateral kidneys

To evaluate renal function changes and risk factors for acute kidney injury (AKI) after percutaneous nephrolithotomy (PCNL) in patients with renal calculi with a solitary kidney (SK) or normal bilateral kidneys (BKs).

How can plasma RNA be used to diagnose prostate cancer

Prostate cancer (PCa) affects male population throughout the world. Advancedor late-stage PCa progresses quickly and leads to a poor prognosis [1]. Therefore, great efforts have been made to detect PCa at an early stage. It has generally been acknowledged that serum prostate-specific antigen (PSA) is a valuable, but not ideal, biomarker for PCa screening and early detection owing to its low specificity. PSA is a prostate-specific marker, not a tumor-specific marker, and it leads to thousands of unnecessary biopsies and overtreatment as well as social economic costs and psychological stress [2]. In order to improve PCa diagnostic accuracy, a variety of biomarkers have been investigated. During the past few decades, extracellular or cell-free ribonucleic acids (RNAs) have been observed at high concentrations in the circulation of cancer patients, indicating their potential use as a novel diagnostic biomarker. Investigations of blood-derived DNA allowed the discovery of genetic and epigenetic mutations or alterations relevant to cancer development and progression. Tumorigenesis and tumor progression are complicated processes that are closely linked to transcriptomic level changes, which may be reflected in circulating RNA alterations. This strong link makes circulating RNAs a promising biomarker with more accuracy and specificity to complement or replace current blood biomarkers. A liquid biopsy is easy to conduct repeatedly with no need for hospitalization, and repeated blood sampling allows for the possibility of detecting circulating RNA changes throughout the natural course of tumor progression and to monitor the treatment response. Extracellular RNAs secreted into the bloodstream are surprisingly stable owing to the packaging of exosomes and proteins [3]. In summary, the analysis of circulating RNA has the potential to serve as a novel and noninvasive diagnostic approach. Although a significant amount of research has focused on circulating RNAs as promising biomarkers for PCa detection and disease prognostication, the origin of cell-free RNA in circulation during cancer development and progression is still not well understood. The increase in plasma/serum RNA may be relevant to apoptosis or necrosis of cancer cells, and fragments of cellular nucleic acid can be actively released into the bloodstream by local or distant tumor cells [4,5]. The proportion of circulating RNAs secreted by tumor cells fluctuates owing to the biological status of the tumor cells. The quantity of circulating RNAs is also dependent on its degradation and clearance rate. Circulating noncoding RNAs (ncRNAs) have also been thought to be derived from peripheral blood cells [6], although other studies have not found a significant association between plasma long ncRNA (lncRNA) concentrations and peripheral hematocytes [5]. Pioneering studies on circulating detectable mRNAs have indicated their potential diagnostic and prognostic value in PCa, but few studies have been reported partly because of the limited biological function of mRNAs in the extracellular space [7]. With the advance of next-generation sequencing through either transcriptome or genome profiling, unprecedented numbers of potential biomarkers have been discovered. ncRNAs, which were previously regarded as junk RNAs or dark matter in the genome, have now begun to help unravel the puzzle of almost all biological events. Direct RNA sequencing of paired control and cancer patient plasma or plasma exosomes may provide a straightforward strategy to discover novel biomarkers. The measurement of blood-derived microRNAs (miRNAs) via a stable and consistent approach was first reported in 2008 [8]. Researchers revealed that these remarkably stable circulating miRNAs existed in exosomes, microvesicles, and apoptotic bodies and they interacted with Ago proteins, which could protect them from degradation by ribonuclease [9]. Subsequent attempts investigated the changes in circulating miRNAs as potentially useful biomarkers for the diagnosis, staging, and prediction of PCa outcomes [7]. Plasma miR-141 detected by quantitative real-time polymerase chain reaction was able to differentiate patients with PCa from healthy controls. A multicenter analysis indicated that miR-141 was unable to identify PCa patients; however, a miR-141-based panel showed a robust diagnostic value when distinguishing between PCa and benign prostate hyperplasia (BPH) populations [10]. A recent study on the RNA sequencing of castrationresistant prostate cancer (CRPC) patients investigated whether circulating exosomal miRNAs could be used as biomarkers to predict overall survival [11]. The results showed that plasma miRNAs are promising sensitive biomarkers for providing a prognosis in patients with CRPC.