Background: The surgical management and outcomes of renal cell carcinoma (RCC) with venous tumor thrombus (VTT) have been reported in limited sample size, and there remain discrepancies over the factors that influence oncologic outcomes after radical nephrectomy with thrombectomy (RNTE). The aim of the study was to analyze the outcomes of the patients with RCC with VTT in our institution and identify the independent prognostic factors. Methods: Patients with RCC with VTT were enrolled for the study from February 2015 to December 2018. All patients underwent RNTE. Clinical data were compared using Mann-Whitney U test and the chi-square test for continuous and categorical variables respectively. Survival analysis was estimated using the Kaplan-Meier method. Univariable and multivariable survival analyses were performed using Cox regression model. Results: 121 patients (91 men & 30 women) were identified with a median age of 60 years. VTT level was 0 in 25 patients, I in 20, II in 50, III in 12 and IV in 14. The median follow-up time was 24 months. During the follow-up period, 51 (42%) patients died and 69 (57%) patients experienced recurrence or metastasis. The 3-year and 5-year over-all survival (OS) were 58 and 39%. Among the several factors examined, positive lymph node (P = 0.016), metastasis at surgery (P = 0.034), tumor necrosis (P = 0.023) and sarcomatoid differentiation (P < 0.001) were demonstrated as independent significant risk factors on multivariable analysis. Conclusion: The OS was poor for patients with RCC with VTT. Rather than VTT level, positive lymph node, metastasis at surgery, tumor necrosis and sarcomatoid differentiation were independent prognostic predictors.

KLF2, a member of the Kruppel-like factor (KLF) family, is thought to be a tumor suppressor in many kinds of malignant tumors. Its functions in prostate cancer (PCa) are unknown. This study aimed to explore the role of KLF2 in the migration and invasion of PCa cells. The expression of KLF2 was measured by immunohistochemistry in PCa tissues and in paired non-tumor tissues. KLF2 and MMP2 expression in cells was measured by Western blot and RT-qPCR. Adenoviruses and siRNAs were used in cell function tests to investigate the role of KLF2 in regulating MMP2. Interactions between KLF2 and MMP2 were analyzed by a luciferase activity assay. The present study, for the first time, identified that KLF2 was downregulated both in PCa clinical tissue samples and in cancer cell lines. The overexpression of KLF2 inhibited the migration and invasion of PCa cells via the suppression of MMP2.This study demonstrates that KLF2 might act as a tumor suppressor gene in PCa and that the pharmaceutical upregulation of KLF2 may be a potential approach for treatment.

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Background: Prostate cancer (PCa) is a common malignant tumor of the genitourinary system. Clinical intervention in advanced PCa remains challenging. Tropomyosins 2 (TPM2) are actin-binding proteins and have been found as a biomarker candidate for certain cancers. However, no studies have explored the role of TPM2 in PCa and its regulatory mechanism. Methods: TPM2 expression was assessed in Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) PCa patient dataset. The effect of TPM2 on PCa progression was assessed in vitro and in vivo by quantifying proliferation, migration, invasion and tumor growth assays, and the mechanism of TPM2 in PCa progression was gradually revealed by Western blotting, immunoprecipitation, and immunofluorescence staining arrays. Results: TPM2 was found to be severely downregulated in tumor tissues of PCa patients compared with tumor-adjacent normal tissues. In vitro experiments revealed that TPM2 overexpression inhibited PCa cell proliferation, invasion and androgen-independent proliferation. Moreover, TPM2 overexpression inhibited the growth of subcutaneous xenograft tumors in vivo. Mechanistically, this effect was noted to be dependent on PDZ-binding motif of TPM2. TPM2 competed with YAP1 for binding to PDLIM7 through the PDZ-binding motif. The binding of TPM2 to PDLIM7 subsequently inhibited the nuclear transport function of PDLIM7 for YAP1. YAP1 sequestered in the cytoplasm phosphorylated at S127, resulting in its inactivation or degradation which in turn inhibited the expression of YAP1 downstream target genes. Conclusions: This study investigated the role of TPM2, PDLIM7, and YAP1 in PCa progression and castration resistance. TPM2 attenuates progression of PCa by blocking PDLIM7-mediated nuclear translocation of YAP1. Accordingly, targeting the expression or functional modulation of TPM2, PDLIM7, or YAP1 has the potential to be an effective therapeutic approach to reduce PCa proliferation and prevent the progression of castration-resistant prostate cancer (CRPC).