Yinjie Zhu

Platelet to lymphocyte ratio as an independent prognostic indicator for prostate cancer patients receiving androgen deprivation therapy

BackgroundPlatelet to Lymphocyte ratio (PLR) is thought to be associated with a worse outcome in multiple types of cancer. However, the prognostic significance of PLR has not been investigated in the prostate cancer (PCa) patients receiving hormonal therapy. The objective of this study was to determine the prognostic value of PLR in PCa patients treated with androgen deprivation therapy (ADT).MethodsTwo-hundred-ninety prostate cancer patients who had undergone ADT as first-line therapy were retrospectively analyzed. The blood cell counts were performed at the time of diagnosis. PLR was calculated as the ratio of platelet count to lymphocyte count. Patients were categorized in two groups using a cut-off point of 117.58 as calculated by the receiver-operating curve analysis. Correlations between PLR and clinical characteristics were analyzed. Meanwhile, univariate and multivariate cox regression analyses were performed to determine the associations of PLR with progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). Prognostic accuracy was evaluated with the Harrell concordance index.ResultsThe differences of age, serum prostate-specific antigen (PSA) level, Gleason score, risk stratification and incidence of metastasis between low PLR group (<117.58) and high PLR group (≥117.58) were not statistically significant (p > 0.05). Multivariate analyses identified PLR as an independent prognostic factor for PFS (hazard ratio (HR) = 1.581, p = 0.013), CSS (HR = 1.768, p = 0.037) and OS (HR = 1.650, p = 0.044). The addition of PLR to the final model improved predictive accuracy (c-index: 0.747, 0.801 and 0.768) for PFS, CSS and OS compared with the clinicopathological base model (c-index: 0.730, 0.778 and 0.746), which included Gleason score and incidence of metastasis.ConclusionsPLR might play a significant role in the prognosis of PCa patients treated with ADT. Thus, we recommend adding PLR to traditional prognostic model to improve the predictive accuracy.

Evaluation of expressed prostatic secretion and serum using surface-enhanced Raman spectroscopy for the noninvasive detection of prostate cancer, a preliminary study

Surface-enhanced Raman spectroscopy (SERS) involving expressed prostatic secretion (EPS) and serum was investigated; the objective was to determine if this approach could distinguish prostate cancer from benign prostatic hyperplasia. A total of 120 SERS spectra for EPS and 96 spectra for serum were gathered from patients within a prospective contemporary biopsy cohort. Significant differences in spectra between prostate cancer and benign prostatic hyperplasia were tentatively assigned to component changes in EPS and serum samples. Principal component analysis and linear discriminate analysis were utilized to evaluate the spectral data for EPS and serum, to build diagnostic algorithms. The leave-one-out cross-validation method was used to validate the diagnostic algorithms; it revealed diagnostic sensitivities of 75% and 60%, specificities of 75% and 76.5%, and accuracies of 75% and 68% for EPS and serum, respectively. The results suggest that EPS and serum SERS analysis could be a potential tool for prostate cancer detection.

Prognostic nutritional index predicts initial response to treatment and prognosis in metastatic castration‐resistant prostate cancer patients treated with abiraterone

To determine if prognostic nutritional index (PNI) and its variation could predict initial response to treatment and prognosis in metastatic castration‐resistant prostate cancer (mCRPC) patients treated with Abiraterone (AA).

Influence of abiraterone acetate on neuroendocrine differentiation in chemotherapy-naive metastatic castration-resistant prostate cancer

To determine the influence of abiraterone Acetate (AA) on neuroendocrine differentiation (NED) in patients with chemotherapy‐naive metastatic castration‐resistant prostate cancer (mCRPC).

Systemic immune-inflammation index predicts the combined clinical outcome after sequential therapy with abiraterone and docetaxel for metastatic castration-resistant prostate cancer patients

To compare the antitumor effect of abiraterone (AA) followed by docetaxel‐prednisone (DP) or vice versa in metastatic castration‐resistant prostate cancer (mCRPC) patients, and explored factors that might predict combined PSA‐PFS, combined rPFS and OS.

Insulinoma-associated protein 1 is a novel sensitive and specific marker for small cell carcinoma of the prostate

The correct diagnosis of small cell carcinoma (SCC) of the prostate is critical because of its aggressive behavior and poor prognosis. The histopathologic diagnosis could be challenging without neuroendocrine markers, which currently has limitations. Insulinoma-associated protein 1 (INSM1), a zinc-finger transcription factor, is considered to play an important role in the development of several neuroendocrine precursor cells. Its diagnosis value has only recently been evaluated. In this study, we analyzed the expression of INSM in three high-throughput RNA sequencing data sets and performed INSM1 immunohistochemistry on a large series of prostatic SCCs and non-neuroendocrine prostate tissues. To validate its possible utility as a diagnostic marker, the performance of chromogranin and synaptophysin was used for comparison. We found INSM1 mRNA is up-regulated in neuroendocrine prostate carcinoma samples from the published data sets. The results were verified by the immunohistochemistry performance. INSM1 was positive in 92.3% of prostatic SCCs, compared with 53.8% positive for chromogranin, and 84.6% positive for synaptophysin. INSM1 was also stained all of the mixed SCC-acinar adenocarcinomas and metastatic SCCs progression from acinar adenocarcinoma. Only 3.4% of benign prostate tissues and 4.0% of prostate adenocarcinomas were INSM1 positive. Our data suggest that INSM1 is a novel sensitive and specific marker for detection of SCC of the prostate. Application of INSM1 in clinical pathologic diagnosis will be valuable.

Serum Pre-Albumin Predicts the Clinical Outcome in Metastatic Castration-Resistant Prostate Cancer Patients Treated With Abiraterone

Objective To determine the prognostic utility of serum pre-albumin in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone (AA). Patients and Methods 112 chemotherapy pretreated or chemotherapy-naive patients were scheduled for systemic treatment with AA. Serum pre-albumin levels were measured before and after 3 months of AA treatment. Univariate and multivariate analyses were performed to determine prognostic factors that were associated with PSA progression-free survival (PSA-PFS), radiographic PFS (rPFS) and overall survival (OS). The Harrell concordance index with variables only or combined pre-albumin data were used to evaluate the prognostic accuracy. Results The group of patients with baseline pre-albumin value ≥20mg/dL had a longer OS, PSA-PFS, rPFS than those with pre-albumin value <20mg/dL. Based on the values of pre-albumin before and after 3 months of AA treatment, we divided these patients into 4 groups: high-high, high-low, low-high and low-low group. High- high group showed a significantly better OS, PSA-PFS, rPFS than other 3 groups. In multivariate analysis, low pre-albumin level remained significant predictors of OS (HR, 13.2; P<0.001), rPFS (HR, 3.7; P=0.003) and PSA-PFS (HR, 8.7; P<0.001). The estimated c-index of the multivariate model for OS increased from 0.814 without pre-albumin to 0.845 when pre-albumin added. Conclusion Low pretreatment serum pre-albumin is a negative independent prognosticator of survival outcomes in mCRPC treated with AA and also increases the accuracy of established prognostic model. Serial pre-albumin evaluation might help clinicians guide clinical treatment of mCRPC patients.

Albumin and Fibrinogen Combined Prognostic Grade Predicts Prognosis of Patients with Prostate Cancer

Background: The nutritional status and systemic inflammation are thought to be associated with outcome in multiple types of cancer. The objective of this study was to determine the prognostic value of pretreatment albumin and fibrinogen combined prognostic grade (AFPG) in prostate cancer (PCa). Methods: 462 prostate cancer patients who had undergone androgen deprivation therapy (ADT) as first-line therapy at four cencters were retrospectively analyzed. The serum albumin levels and plasma fibrinogen levels were measured at the time of diagnosis. The AFPG was calculated according to albumin and fibrinogen levels dichotomized by optimal cut-off values or clinical reference values. Univariate and multivariate cox regression analyses were performed to determine the associations of AFPG with progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). Prognostic accuracy was evaluated with the Harrell concordance index. Results: Multivariate analyses identified AFPG as an independent prognostic indicator for PFS, CSS and OS (each p < 0.01). According to optimal cut-off values, the addition of AFPG to the final models improved predictive accuracy for PFS, CSS and OS compared with the clinicopathological base models, which included Gleason score and incidence of metastasis. Moreover, AFPG according to optimal cut-off values was a better prognostic predictor than albumin levels alone or fibrinogen levels alone or AFPG according to clinical reference values. Conclusion: Decreased AFPG could predict a significantly poor prognosis in patients with PCa. Thus, we recommend adding AFPG according to optimal cut-off values to traditional prognostic model to improve the predictive accuracy.

PRKAR2B promotes prostate cancer metastasis by activating Wnt/β-catenin and inducing epithelial-mesenchymal transition

Castration‐resistant prostate cancers (CRPC) that occur after the failure of androgen‐blocking therapies cause most of the deaths in prostate cancer (PCa) patients. In a previous study we identified that PRKAR2B expression is upregulated in CRPC and possesses potentials to develop CRPC. Here we further investigated the underlying mechanism of PRKAR2B in regulating prostate cancer metastasis. We established an androgen‐independent LNCaPcell line (LNCaP‐AI), and investigated the function of PRKAR2B on regulating cell invasion in vitro and in vivo. We found that PRKAR2B expression was markedly increased in LNCaP‐AI cells and metastatic CRPC (mCRPC) tissues compared to LNCaP cells and primary PCa specimens, respectively. PRKAR2B level was significantly correlated with the Gleason score and lymph nodes metastasis in PCa. In vitro, PRKAR2B overexpression promoted cell invasion, whereas knockdown of PRKAR2B in CRPC cells inhibited cell invasion. PRKAR2B overexpression also promoted tumor metastasis in vivo. PRKAR2B resulted in a decreased expression of E‐cadherin and an increased expression of Vimentin, N‐cadherin, Fibronectin, indicating that PRKAR2B induced epithelial‐mesenchymal transition (EMT). PRKAR2B activated Wnt/β‐catenin signaling in CRPC cells. More important, inhibition of Wnt/β‐catenin attenuated PRKAR2B‐induced EMT and cancer cells invasion. Our results provided novel insights to PRKAR2B‐driven CRPC cell invasion and indicated that PRKAR2B might be served as a potential target for CRPC therapy.

PD39-12 RISK FACTORS RELATED TO POST-PROSTATECTOMY INCONTINENCE AND DEVELOPMENT OF PREDICTIVE NOMOGRAMS

and UDI-6 totals had 0.878 correlation, while VUSS AUA-SI had 0.72 correlation. CONCLUSIONS: VUSS content correlated well with UDI-6 total scores. Comprehension would benefit from increasing contrast details in pictograms. Further development can add to the ability to measure womens LUTS on a global scale to reduce language and literacy barriers to urologic history taking. Next steps will incorporate changes from this validation and testing in a low resource environment.