Clear cell renal cell carcinoma (ccRCC) is the most aggressive RCC subtype with high metastasis, chemotherapy and radiotherapy resistance, and poor prognosis. This study attempted to establish the deregulations of miR-4521 and FAM129A together with their correlation to and mechanism of regulation of ccRCC development and progression. FAM129A acted as tumor promotor and miR-4521 acted as a suppressor in ccRCC. As measured in surgical tumorous tissues from ccRCC patients, FAM129A overexpression and miR-4521 deficiency together contributed to ccRCC progression by promoting advances in patients’ TNM stage and Fuhrman grade. Both the FAM129A knockdown and miR-4521 overexpression could reduce the in vitro migration and invasion abilities of renal cancer cells 786-O and ACHN, through the TIMP-1/MMP2/MMP9 pathway and could decrease their proliferation by promoting their apoptosis through the MDM2/p53/Bcl2/Bax pathway. By directly targeting the 3′-UTR domain of FAM129A , miR-4521 was negatively correlated with FAM129A /FAM129A levels in ccRCC progression and renal cancer cell malignancies. This work establishes the miR-4521-FAM129A axial regulation mechanism in ccRCC. Micro-4521 deficiency leads to FAM129A /FAM129A upregulation, which synergistically enhances the migration and invasion of renal cancer cells due to the induced decrease of TIMP-1 and increases of MMP2 and MMP9, and increases their growth through escaping apoptosis by suppressing p53 by way of upregulation of induced MDM2. The current work provides new clues to assist fundamental research into the diagnosis and treatment of ccRCC.
Background: D'Amico high-risk prostate cancer (Pca) patients experience poor and heterogeneous oncological outcomes. This heterogeneity highlights a need to extensively explore factors associated with poor outcomes to guide decision-making. Objective: To assess predictors of biochemical recurrence (BCR)-free survival in high-risk patients following radical prostatectomy (RP), and subsequently establish a model predicting outcomes. Methods: We retrospectively identified D'Amico high-risk non-metastatic Pca patients who underwent RP between 2013 and 2019 in our hospital. We collected data including PSA level, clinical stage, biopsy Gleason score (GS), number of D'Amico high-risk factors (RF), the inflammatory status (Neutrophil-to-lymphocyte ratio [NLR], derived NLR [dNLR], platelet-to-lymphocyte ratio [PLR] and LDH). Kaplan-Meier methods were used to analyze BCR-free survival. Univariate and multivariate analyses were performed using Cox proportional hazards model to evaluate the association between clinicopathological parameters and BCR-free survival. Results: The median follow-up time for the 101 patients' cohort was 26 months (range: 3-81 months). The number of RF (1RF vs. ≥2RF), biopsy GS (<8 vs. ≥8), clinical stage (≤cT2c vs. >cT2c), pathological stage, and the presence of adverse pathological features were significant predictors of BCR (P < 0.05). Other parameters including inflammatory status (dNLR, NLR, PLR, and LDH) were not of predictive value. On multivariable analysis, biopsy GS (<8 vs. ≥8; HR 2.439) and clinical stage (≤cT2c vs. >cT2c; HR 3.271) were the independent predictors of BCR. Based on these two independent predictors, patients were stratified into three risk subgroups: favorable (0 risk factor; 47% of patients), intermediate (1 risk factor; 42 %), unfavorable (2 risk factors; 11%). The intermediate and unfavorable subgroups have a significantly shorter median BCR-free survival compared to the favorable subgroup (P < 0.001). Conclusion: Several factors are associated with BCR. Clinical stage (≤cT2c vs. >cT2c) and biopsy GS (<8 vs. ≥8) are the independent predictors of BCR. The stratification of high-risk patients into risk subgroups based on these two predictors shows that the intermediate and unfavorable subgroups have a significantly shorter median BCR-free Nkengurutse et al. BCR-Free Survival in High-Risk Pca survival compared to the favorable subgroup. The preoperative stratification model may help urologists and patients during decision-making. In non-metastatic high-risk patients, preoperative inflammatory markers (NLR, dNLR, PLR, and LDH) are not of prognostic value.
Renal cell carcinoma (RCC) metastasizing to the heart with inferior vena cava (IVC) involvement is well-documented. However, its metastasis to the right heart without venous involvement is very rare. To the left atrium, metastasis is even rarer with only a few cases reported in medical literature. Herein, we report a case of a 56-year-old man who presented to our department for the treatment of a right renal mass and a right adrenal mass discovered on a follow-up plain computed tomography (CT) 13 years after left laparoscopic radical nephrectomy. During the workup, a transthoracic echocardiography (TTE) revealed a left atrial mass with a suspicion of a myxoma. This finding prompted a cardiac surgery consult which proposed a surgical removal of the mass. Intraoperatively, the tumor was found to invade the coronary sinus as well. The entire tumor was successfully removed and surgical repair of the unroofed coronary sinus was performed. Pathological examination of the tumor along with immunohistochemistry–showing positivity for CAIX, CD10, Vimentin, and PAX-8–pointed to a diagnosis of metastatic clear cell RCC. Eight months postoperatively, he was free of any symptom. In conclusion, RCC metastasizing to the left atrium is extremely rare. A comprehensive search revealed only nine reports in the literature. We report, to our knowledge, the first case of RCC metastasizing to the left atrium with concomitant invasion of coronary sinus. Surgical resection combined with unroofed coronary sinus repair allowed a complete removal of the tumor. In patients with a history of RCC, a metastasis should be thought of when a left atrial mass is present.
High SKA1 expression is associated with early recurrence and progression in patients with NMIBC, indicating SKA1 may serve as a promising prognostic biomarker for this disease.
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