ABSTRACT
BACKGROUND: The American Joint Committee on Cancer (AJCC) 8th staging system of prostate cancer may be insufficient in predicting the prognosis of some staged patients. This study aimed to modify the AJCC 8th staging system in patients with advanced prostate cancer. METHODS: Data of patients with advanced prostate cancer from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016 were enrolled in this cohort study. All patients were divided into the training set and the testing set with a ratio of 6:4. Multivariate Cox survival model was utilized to obtain the nomogram score for each stage variable. The modified staging system was based on the total nomogram score. The C-index and Kaplan-Meier (K-M) curves were used to show the prognostic prediction effect of patients with different staging systems. RESULTS: A total of 28,006 patients were included for analysis. T stage, N stage, M stage, primary Gleason pattern score, secondary Gleason pattern score, and PSA level were included as stage variables. Patients with AJCC stage III C [hazard ratio (HR) = 4.17, 95% confidence interval (CI), 3.39-5.13] and AJCC stage IV B (HR = 3.19, 95%CI, 1.79-5.69) were associated with worse prognosis compared with those of AJCC stage III B, while no statistical significance was found in patients with stage IV A (P > 0.05). In terms of the modified staging system, patients with modified stage III C (HR = 2.06, 95%CI, 1.46-2.92), modified stage IV A (HR = 6.91, 95%CI, 4.81-9.94), and modified stage IV B (HR = 21.89, 95%CI, 14.76-32.46) were associated with a poorer prognosis compared with patients with modified stage III B. The prognostic ability (C-index) of the modified staging system (0.789; 95%CI, 0.777-0.801) was better than that of the AJCC 8th edition system (0.762; 95%CI, 0.748-0.776) (0.789 vs. 0.762, P = 0.004). The K-M curves indicated that the modified staging system may be distinguished prognostic differences in patients with different stages. CONCLUSION: Modified staging system may be better than AJCC 8th staging system for predicting prognosis in prostate cancer patients. The AJCC 8th staging system should be further optimized.
Subject(s)
Prostatic Neoplasms , Male , Humans , SEER Program , Neoplasm Staging , Cohort Studies , PrognosisABSTRACT
Prostate cancer (PC) is the most common type of newly diagnosed malignancy in men. Combined chemotherapy has been shown to be an effective strategy for the treatment of PC therapy. Lipid-polymer hybrid nanoparticles (LPNs) are core-shell nanoparticles composed of a polymer core and a lipid shell, which are reported to provide significant advantages for combined PC therapy. This study synthesized an aptamer conjugated ligand and designed an aptamer-functionalized, curcumin (CUR) and cabazitaxel (CTX) co-delivered LPNs (APT-CUR/CTX-LPNs). APT-CUR/CTX-LPNs had a mean size of 121.3 ± 4.2 nm and a positive surface charge (23.5 ± 2.6 mV). Both CUR and CTX were sustained released from LPNs. Aptamer-functionalized APT-CUR/CTX-LPNs exhibited good cell inhibition ability, high tumor accumulation, and remarkable tumor inhibition efficiency at the drug ratio of 2:5 (CUR:CTX). The novel LPNs offers great promise for the double drugs delivery to the prostate cancer cells and tumor xenograft in vivo, showing the potential of synergistic combination therapy for prostate cancer.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Aptamers, Nucleotide/chemistry , Drug Delivery Systems , Prostatic Neoplasms/drug therapy , Animals , Antineoplastic Combined Chemotherapy Protocols/chemistry , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Cell Line, Tumor , Curcumin/administration & dosage , Drug Carriers/chemistry , Humans , Lipids/chemistry , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Nanoparticles , Polymers/chemistry , Taxoids/administration & dosage , Xenograft Model Antitumor AssaysABSTRACT
MicroRNAs (miRNAs) are well established key players in tumorigenesis. Their emergence as potential diagnostic and prognostic biomarkers for cancer has demonstrated the importance of miRNAs in cancer biology. Although miR486 is implicated in many types of cancer, its role in renal cell carcinoma (RCC) remains undetermined. In the present study, realtime quantitative PCR (qPCR), wound scratch assay, cell proliferation assay, Transwell migration assay and flow cytometry were utilized to detect the miR486 transcript and its role in proliferation, migration and apoptosis in RCC. The relationship between miR486 expression and clinicopathological variables or overall survival was analyzed using 96 formalinfixed paraffinembedded (FFPE) RCC samples. The results of the present study revealed significant upregulation of miR486 in RCC tissues and cell lines. Moreover, ectopic expression of miR486 promoted cell proliferation, mobility and inhibited apoptosis in 786O and ACHN cell lines. In addition, the Cox proportional hazard regression analysis revealed that patients with low expression of miR486 exhibited a markedly longer overall survival in the univariate and multivariate analyses. In conclusion, our findings indicate that miR486 may serve as a novel prognostic biomarker but may also be applied as a new therapeutic approach for the treatment of RCC.