KLF9 inhibits the proliferation, invasion, and migration of renal cell carcinoma through the SDF-1/CXCR4 axis.

Altered Krüppel-like factor 9 (KLF9) expression can regulate the progression of several cancers, including renal cell carcinoma (RCC). This study was conducted to investigate the role of KLF9 in the proliferation, invasion, and migration of RCC cells via regulation of stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4). The expression patterns of KLF9, SDF-1, and CXCR4 in the experimental cell lines were determined by real-time quantitative polymerase chain reaction and Western blotting. After transfection of the KLF9 siRNA and KLF9 pcDNA, cell proliferation, invasion, and migration were evaluated by experiments including cell counting kit-8, colony formation, and Transwell assays. The binding of KLF9 to the SDF-1 promoter was analyzed by chromatin immunoprecipitation and dual-luciferase assay. The rescue experiment was performed using the recombinant SDF-1 protein and KLF9 pcDNA. KLF9 was downregulated in the RCC cells. KLF9 knockdown induced the proliferation, invasion, and migration of RCC cells, whereas KLF9 overexpression elicited the opposite roles. Mechanically, KLF9 bound to the SDF-1 promoter, repressed SDF-1 transcription, and reduced the SDF-1/CXCR4 expression levels. Activation of the SDF-1/CXCR4 axis attenuated the inhibitory role of KLF9 overexpression in RCC cell growth. Ordinarily, KLF9 suppressed the proliferation, invasion, and migration of RCC cells by repressing the SDF-1/CXCR4 signaling.

Nomogram Incorporating Contrast-Enhanced Ultrasonography Predicting Time to the Development of Castration-Resistant Prostate Cancer.

BACKGROUND: It is valuable to predict the time to the development of castration-resistant prostate cancer (CRPC) in patients with advanced prostate cancer (PCa). This study aimed to build and validate a nomogram incorporating the clinicopathologic characteristics and the parameters of contrast-enhanced ultrasonography (CEUS) to predict the time to CRPC after androgen deprivation therapy (ADT). METHODS: Patients with PCa were divided into the training (n = 183) and validation cohorts (n = 37) for nomogram construction and validation. The clinicopathologic characteristics and CEUS parameters were analyzed to determine the independent prognosis factors and serve as the basis of the nomogram to estimate the risk of 1-, 2-, and 3-year progress to CRPC. RESULTS: T stage, distant metastasis, Gleason score, area under the curve (AUC), prostate-specific antigen (PSA) nadir, and time to PSA nadir were the independent predictors of CRPC (all P < 0.05). Three nomograms were built to predict the time to CRPC. Owing to the inclusion of CEUS parameter, the discrimination of the established nomogram (C-index: 0.825 and 0.797 for training and validation datasets) was improved compared with the traditional prediction model (C-index: 0.825 and 0.797), and when it excluded posttreatment PSA, it still obtained an acceptable discrimination (C-index: 0.825 and 0.797). CONCLUSIONS: The established nomogram including regular prognostic indicators and CEUS obtained an improved accuracy for the prediction of the time to CRPC. It was also applicable for early prediction of CRPC when it excluded posttreatment PSA, which might be helpful for individualized diagnosis and treatment.

Association Between Contrast-Enhanced Ultrasound Indicators and Prostate Cancer Biochemical Recurrence After Treatment.

BACKGROUND: Some patients with prostate cancer (PCa) will experience biochemical recurrence (BCR) after treatment. Current researches have identified the influencing factors of BCR, but these factors are difficult to quantify and hence unable to accurately predict the BCR in PCa patients. OBJECTIVE: To explore the value of contrast-enhanced ultrasound (CEUS) indicators in predicting the BCR after treatment by evaluating the association between them. PATIENTS AND METHODS: In a retrospective cohort study, 157 PCa patients were recruited and received prostate specific antigen (PSA) measurement, CEUS, pathological classification, and immunohistochemistry after puncture biopsy. PCa patients with BCR were included in the recurrence group, while the remaining patients were included in the non-recurrence group after a 5-year follow-up. The clinical characteristics and CEUS indicators were compared between the two groups, and the multivariable COX regression was used for screening the influencing factors of BCR. Receiver operating characteristic (ROC) curves were used to analyze the value of potential factors in predicting BCR. The effect of the combined prediction model was explored to improve the accuracy of the prediction. RESULTS: Twelve patients are lost during the follow-up period and the final analysis included 145 patients. The 5-year BCR rate of PCa patients was 27%, with 43 patients in the recurrence group and 102 patients in the non-recurrence group. Multivariate analysis showed that lymph node metastasis (P<0.001), distant metastasis (P<0.001), Gleason score (P<0.001), pretreatment PSA (P<0.001), treatment method (P<0.001), peak intensity (PI) (P=0.001), and time to peak (TTP) (P=0.003) were independent influencing factors for BCR after treatment. ROC analysis showed that the AUCs of all indicators in predicting BCR were not high (all <0.9). The combination of lymph node metastasis, Gleason score, pretreatment PSA, and treatment method can improve the predictive accuracy (AUC = 0.85), but the AUC was still under 0.9. The combined prediction model including CEUS time-intensity curve (TIC) indicators (PI and TTP) could accurately predict the BCR after treatment (AUC=0.953). The sensitivity and specificity were 93.02% and 88.24%, respectively. CONCLUSION: The prediction model including TIC indicators and common influencing factors can more accurately predict the BCR in PCa patients.

[Radical retropubic prostatectomy for prostate cancer with pelvic lymph node metastasis].

OBJECTIVE: To investigate the safety and effectiveness of radical retropubic prostatectomy (RRP) with adjuvant androgen deprivation or external radiotherapy in the treatment of prostate cancer (PCa) with pelvic lymph node metastasis (PLNM). METHODS: Twenty PCa patients underwent bilateral pedal lymphangiography (PLG) preoperatively, and 11 of them received lymph node aspiration for examination of the mRNA expressions of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) in the lymph fluid by real-time RT-PCR. All the patients were treated by RRP with extended dissection of pelvic lymph nodes, and 3 of them by external radiotherapy in addition after recovery from urinary incontinence because of positive surgical margins, followed by adjuvant androgen deprivation therapy. RESULTS: Real-time RT-PCR showed positive mRNA expressions of PSA and PSMA in the lymph fluid of the 11 patients, all pathologically confirmed with PLNM. The median intraoperative blood loss was 575 ml, with blood transfusion for 5 cases. Positive surgical margin was found in 3 cases, lymphorrhagia in 2 and urinary leakage in another 2 each. There were no such severe complications as vascular injury and rectum perforation. The patients were followed up for 6－48 (mean 42) months, during which, biochemical recurrence was observed in 12 cases at a median of 12 months postoperatively and 2 patients died at 12 and 48 months respectively. CONCLUSIONS: Bilateral PLG and lymph node aspiration for examination of the mRNA expressions of PSA and PSMA in the lymph fluid help to confirm PLNM preoperatively. Radical retropubic prostatectomy with adjuvant androgen deprivation or external radiotherapy is safe and effective for the treatment of PCa with PLNM, but it should be chosen cautiously for those with Gleason 5+5.

[Experience in reducing intraoperative blood loss in radical retropubic prostatectomy].

OBJECTIVE: To search for an effective method of reducing intraoperative blood loss in radical retropubic prostatectomy (RRP). METHODS: We performed RRP for 100 patients with prostate cancer, 50 (group A) with the Walsh or Poor method for handling the dorsal venous complex (DVC), and the other 50 (group B) through the following three additional procedures for hemostasis: first placing a #7 prophylactic suture in the distal position of DVC, then ligating the vascular bundle of the prostatic apex with continuous 4-0 Vicryl sutures, and lastly placing a 4-0 absorbable suture followed by freeing the neurovascular bundle (NVB) or freeing NVB before suturing the remained levator ani myofascia and the deep layer of Denovilliers' fascia above the rectal serosa with 4-0 Vicryl. We assessed the effects of the three hemostatic methods in RRP by comparing the volumes of intraoperative blood loss and transfusion, operation time and perioperative levels of hemoglobin. RESULTS: There were no significant differences between groups A and B in age, PSA, Gleason score, clinical stage, prostate volume, operation time and perioperative hemoglobin levels (P>0.05). The volumes of intraoperative blood loss and transfusion were markedly higher in group A ([1103.00 +/- 528.03] ml and [482.00 +/- 364.60] ml) than in B ([528.00 +/- 258.96] ml and [140.00 +/- 266.28] ml) (P<0.05). CONCLUSION: Intraoperative blood loss in RRP could be significantly decreased by placing a prophylactic hemostatic suture in the distal position of DVC, continuous suture of the vascular bundle of the prostatic apex after cutting off the urethra, and placing a fine absorbable suture above NVB or continuous suture of the remained levator ani mony fascia and the deep layer of Denovilliers'fascia above the rectal serosa with absorbable sutures after freeing NVB.