Xu Dong Yao

Serum miRNA-21: elevated levels in patients with metastatic hormone-refractory prostate cancer and potential predictive factor for the efficacy of docetaxel-based chemotherapy.

miR‐21 has been recognized as an “onco‐microRNA” with the activity of negatively modulating the expression of tumor‐suppressor genes. However, its role in prostate cancer (CaP) has not been well‐documented. We designed this study to assess the potential function of serum miR‐21 in the progression of CaP.

Involvement of microRNA-21 in mediating chemo-resistance to docetaxel in androgen-independent prostate cancer PC3 cells.

AbstractAim:To investigate whether microRNA-21 was involved in mediating the chemoresistance of prostate cancer cells to docetaxel.Methods:A microarray technique was used to determine the miRNA profile in docetaxel-resistant PC3 cells. Real-time PCR was used to confirm the array results. miR-21 mimics and inhibitors were synthesized and introduced to cells using Lipofectamine 2000. Cell proliferation was examined with the CCK-8 assay. Luciferase reporter containing PDCD 3′UTR was constructed and the activity was detected by a dual luciferase assay. PDCD4 protein expression was evaluated using Western blot.Results:A docetaxel-resistant prostate cancer PC3 cell line (PC3R) was established . Using microarrays, miR-21 was found to be up-regulated in PC3R cells. Ectopic expression of miR-21 increased the resistance to docetaxel in PC3 wild type cells. In contrast, silencing of miR-21 in PC3R cells sensitized the cells to docetaxel. The IC50 values for miR-21-silencing cells and control cells were 28.31 and 35.89 nmol/L, respectively. PDCD4, a direct target gene of miR-21, could mediate chemoresistance to docetaxel in PC3 cells.Conclusion:Our findings suggest that miR-21 contributed to the resistance of PC3 cells to docetaxel, and that targeting miR-21 may offer a promising therapeutic approach in sensitizing prostate cancer to docetaxel treatment.

A multiplex model of combining gene‐based, protein‐based, and metabolite‐based with positive and negative markers in urine for the early diagnosis of prostate cancer

Multiplex urine‐based assay emerged outperforms single biomarker (e.g., prostate‐specific antigen, PSA) for predicting prostate cancer (CaP), whereas its combined mode has to be fully optimized. Our aim is to determine whether a strategy of combining gene‐based, protein‐based, metabolite‐based with positive, negative makers in urine could optimize a multiplex model for detecting CaP.

Predicting Pelvic Lymph Node Metastases in Penile Cancer Patients: A Comparison of Computed Tomography, Cloquet’s Node, and Disease Burden of Inguinal Lymph Nodes

Background: The aim of this study was to evaluate the role of computed tomography (CT), Cloquet’s node, and disease burden of inguinal lymph nodes (LNs) in predicting pelvic lymph node metastases (LNM) of penile cancer. Patients and Methods: Bilateral inguinal lymph node dissection was performed in 73 penile cancer patients and revealed that 33 groin basins exhibited inguinal LNM. Results: Of the 33 groin basins, 16 (48.5%) had pelvic LNM. The sensitivity of pelvic CT in detecting metastatic LNs was 37.5%, and the specificity was 100%. Cloquet’s node had a sensitivity of 30.0% and a specificity of 94.1% in pelvic CT-negative groin basins. Pathological characteristics of the inguinal LNs - number of positive LNs, lymph node ratio (number of positive LNs/total number removed), extranodal extension and the expression of p53 - were significantly associated with pelvic LNM. Furthermore, enlarged inguinal LNs = 3 in preoperative CT imaging and lymph node size = 3.5 cm in long diameter were prognostic factors for pelvic LNM (p = 0.001 and 0.003, respectively). Conclusion: Pelvic CT imaging and tumor status of Cloquet’s node is of limited use in predicting microscopic pelvic LNM. Pathological characteristics of the inguinal LNs remain the essential indicators of pelvic LNM.

Activation of the mammalian target of rapamycin signalling pathway in prostate cancer and its association with patient clinicopathological characteristics

To evaluate the activation level of the mammalian target of rapamycin (mTOR) signalling pathway in Chinese patients with prostate cancer, as this pathway is over‐activated in many human cancers and is an attractive target for cancer therapy.

External validation of a nomogram using RENAL nephrometry score to predict high grade renal cell carcinoma.

PURPOSE A novel nomogram using the RENAL ([R]adius maximal diameter in cm, [E]xophytic/endophytic properties, [N]earness of the tumor to the collecting system or sinus in mm, [A]nterior/Posterior, [L]ocation relative to the polar lines and [H]ilar) nephrometry score was developed to predict high grade renal cell carcinoma. It showed good performance in internal evaluation. We externally validated the prediction model. MATERIALS AND METHODS We identified a cohort of 391 Chinese patients in whom renal cell carcinoma was surgically resected at our institution from 2008 to 2011. Fuhrman grade was reviewed by an experienced genitourinary pathologist and radiological images were independently assessed by 2 senior urologists. Using a 2-tiered system high grade disease was defined as Fuhrman grade III/IV. The statistical performance of the prediction model was evaluated by discrimination, calibration and clinical usefulness. RESULTS Of the 391 patients 45.5% were considered to have high grade tumors. External validation of the nomogram revealed an AUC of 0.73. The calibration plot showed that the predicted probability of high grade disease had concordance comparable to the observed frequency. On decision curve analysis the prediction model provided a superior net benefit and reduction at a greater than 20% probability threshold. CONCLUSIONS We confirm the predictive value of the nomogram using the RENAL nephrometry score to identify high grade renal cell carcinoma in an independent cohort. Further research is required to evaluate its performance using a head-to-head comparison with renal biopsy results.

Clinicopathological characteristics, management and outcome of metastatic penoscrotal extramammary Paget's disease.

Background  Metastatic penoscrotal extramammary Paget’s disease (EMPD) has seldom been reported in the literature.

Efforts to resolve the contradictions in early diagnosis of prostate cancer: a comparison of different algorithms of sarcosine in urine

Controversial data on sarcosine as a promising biomarker for prostate cancer (PCa) detection are present. The objective was to clarify these discrepancies and reevaluate the potential value of sarcosine in PCa. Sarcosine algorithms (supernatant and sediment sarcosine/creatinine, supernatant and sediment log2 (sarcosine/alanine)) in urine samples from 71 untreated patients with PCa, 39 patients with no evidence of malignancy (NEM) and 20 healthy women and men were quantified by liquid chromatography/tandem mass spectrometry. Although any sarcosine algorithms were significantly higher in PCa patients than in NEM patients (all P<0.05), comparable sarcosine values were measured in healthy women and men. Additionally, neither biopsy Gleason score nor clinical T-stage were correlated with sarcosine algorithms (all P>0.05), and receiver operating characteristic curve analysis indicated that the diagnostic power of any of sarcosine algorithms was nonsignificantly higher than that of serum and urine PSA, but nonsignificantly lower than prostate cancer antigen 3 (PCA3) and the percent-free PSA (%fPSA). Improved diagnostic performances were observed when any of sarcosine algorithms was combined with PCA3 or %fPSA. In conclusion, the predictive power of sarcosine in PCa is modest compared with PCA3 and %fPSA. Sarcosine, which awaits more validation before it reaches the clinic, could be included into the list of candidate PCa biomarkers.

An elevated serum miR-141 level in patients with bone-metastatic prostate cancer is correlated with more bone lesions

The skeleton is the most common metastatic organ in patients with prostate cancer (PCa). Non-invasive biomarkers that can facilitate the detection and monitoring of bone metastases are highly desirable. We designed this study to assess the expression patterns of serum miR-141 in patients with bone-metastatic PCa. Serum samples were collected to measure the miR-141 level in 56 patients, including six with benign prostatic hyperplasia (BPH), 20 with localized PCa and 30 with bone-metastatic PCa (10 with hormone-naive PCa, 10 with hormone-sensitive PCa and 10 with hormone-refractory PCa). A bone scan was performed for each patient with PCa to assess the number of bone lesions. The quantification of serum miR-141 levels was assayed by specific TaqMan qRT-PCR. The results showed that serum miR-141 levels were elevated in patients with bone metastasis (P<0.001). There was no statistically significant difference in the serum miR-141 levels between patients with BPH and patients with localized PCa. Using Kendalls bivariate correlation test, both the Gleason score and the number of bone-metastatic lesions were found to correlate with serum miR-141 levels (P=0.012 and P<0.001, respectively). The serum miR-141 level was found to be positively correlated with alkaline phosphatase (ALP) level in patients with skeletal metastasis, using Pearsons bivariate correlation test. No relationship was found between the serum miR-141 level and the serum prostate-specific antigen (PSA) level. We concluded that serum miR-141 levels are elevated in patients with bone-metastatic PCa and that patients with higher levels of serum miR-141 developed more bone lesions. Furthermore, serum miR-141 levels are correlated with serum ALP levels but not serum PSA levels.

Visceral Obesity and Risk of High Grade Disease in Clinical T1a Renal Cell Carcinoma

PURPOSE Accurate assessment of disease characteristics is a prerequisite for treatment decision making regarding small renal masses. In this study we evaluate the association between visceral obesity and Fuhrman grade in patients with cT1a renal cell carcinoma. MATERIALS AND METHODS We retrospectively collected data on 186 patients with surgically treated cT1a renal cell carcinoma. Single slice computerized tomography was used to measure the area of visceral and subcutaneous adipose tissue. Visceral obesity was calculated as the proportion of visceral adipose tissue to overall adipose tissue. Other analyzed factors included clinical characteristics (age, gender, body mass index and tumor size) and anatomical features of the tumor defined by the R.E.N.A.L. nephrometry score. The association between predictors and high grade disease (Fuhrman grade III or IV) were assessed using logistic regression analyses. RESULTS A total of 47 (25.3%) tumors were classified as high grade. The percentage of visceral adipose tissue was higher in male participants but did not correlate with body mass index, age or tumor size. In univariate analyses the percentage of visceral adipose tissue and tumor size were significantly associated with higher Fuhrman grade. Multivariate analysis showed that the percentage of visceral adipose tissue (OR 1.06, p = 0.0018) and tumor size (OR 1.91, p = 0.047) were independent predictors of high grade cancer. Addition of the percentage of visceral adipose tissue to a model including clinical characteristics and anatomical features of the tumor remarkably improved its discriminatory ability (p = 0.0010). CONCLUSIONS Increased visceral obesity was found to be strongly associated with higher Fuhrman grade in patients with cT1a renal cell carcinoma. Further studies are needed to confirm these findings and discover the underlying biological mechanism.