Background: Clear cell renal cell carcinoma (ccRCC) accounts for 80% of all kidney cancers and has a poor prognosis. Recent studies have shown that copper-dependent, regulated cell death differs from previously known death mechanisms (apoptosis, ferroptosis, and necroptosis) and is dependent on mitochondrial respiration (Tsvetkov et al., Science, 2022, 375 (6586), 1254–1261). Studies also suggested that targeting cuproptosis may be a novel therapeutic strategy for cancer therapy. In ccRCC, both cuproptosis and lncRNA were critical, but the mechanisms were not fully understood. The aim of our study was to construct a prognostic profile based on cuproptosis-associated lncRNAs to predict the prognosis of ccRCC and to study the immune profile of clear cell renal cell carcinoma (ccRCC).Methods: We downloaded the transcriptional profile and clinical information of ccRCC from The Cancer Genome Atlas (TCGA). Co-expression network analysis, Cox regression method, and least absolute shrinkage and selection operator (LASSO) method were used to identify cuproptosis-associated lncRNAs and to construct a risk prognostic model. In addition, the predictive performance of the model was validated and recognized by an integrated approach. We then also constructed a nomogram to predict the prognosis of ccRCC patients. Differences in biological function were investigated by GO, KEGG, and immunoassay. Immunotherapy response was measured using tumor mutational burden (TMB) and tumor immune dysfunction and rejection (TIDE) scores.Results: We constructed a panel of 10 cuproptosis-associated lncRNAs (HHLA3, H1-10-AS1, PICSAR, LINC02027, SNHG15, SNHG8, LINC00471, EIF1B-AS1, LINC02154, and MINCR) to construct a prognostic prediction model. The Kaplan–Meier and ROC curves showed that the feature had acceptable predictive validity in the TCGA training, test, and complete groups. The cuproptosis-associated lncRNA model had higher diagnostic efficiency compared to other clinical features. The analysis of Immune cell infiltration and ssGSEA further confirmed that predictive features were significantly associated with the immune status of ccRCC patients. Notably, the superimposed effect of patients in the high-risk group and high TMB resulted in shorter survival. In addition, the higher TIDE scores in the high-risk group suggested a poorer outcome for immune checkpoint blockade response in these patients.Conclusion: The ten cuproptosis-related risk profiles for lncRNA may help assess the prognosis and molecular profile of ccRCC patients and improve treatment options, which can be further applied in the clinic.

We conducted multiple microarray datasets analyses from clinical and xenograft tumor tissues to search for disease progression-driving oncogenes in prostate cancer (PCa). Sperm-associated antigen 5 (SPAG5) attracted our attention. SPAG5 was recently identified as an oncogene participating in lung cancer and cervical cancer progression. However, the roles of SPAG5 in PCa progression remain unknown. SPAG5 expression level in clinical primary PCa, metastatic PCa, castration resistant PCa, neuroendocrine PCa, and normal prostate tissues was investigated. We established multiple in vivo xenografts models using patient-derived tissues and investigated SPAG5 expression trend in these models. We also investigated the functions of SPAG5 in vivo and in vitro studies. Luciferase reporter assays were performed to investigate potential miRNAs that can regulate SPAG5. We identified that SPAG5 expression was gradually increased in PCa progression and its level was significantly associated with lymph node metastasis, clinical stage, Gleason score, and biochemical recurrence. Our results indicated that SPAG5 knockdown can drastically inhibit PCa cell proliferation, migration, and invasion in vitro and supress tumor growth and metastasis in vivo. We identified that miR-539 can directly target SPAG5. Ectopic overexpression of miR-539 can drastically inhibit SPAG5 expression and the restoration of SPAG5 expression can reverse the inhibitory effects of miR-539 on PCa cell proliferation and metastasis. Our results collectively showed a progression-driving role of SPAG5 in PCa which can be regulated by miR-539, suggesting that miR-539/SPAG5 can serve as a potential therapeutic target for PCa.

Background: Nucleobindin 2 (NUCB2) abnormal expression has been reported in gastric cancer and breast cancer. However, the role of NUCB2 in prostate cancer (PCa) remains unclear. The aim of the present study was to investigate the NUCB2 expression in PCa tissues and adjacent non-cancerous tissues and its potential relevance to clinicopathological variables and prognosis. Methods: NUCB2 mRNA expression was determined by real-time quantitative real time reverse transcriptase polymerase chain reaction in 180 pairs of fresh frozen PCa tissues and corresponding non-cancerous tissues. Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the correlation between NUCB2 expression and prognosis of PCa patients. Results: Our results showed that the expression level of NUCB2 mRNA in PCa tissues was significantly higher than those in non-cancerous tissues. Our results indicated that the high expression of NUCB2 in PCa was associated with lymph node metastasis, preoperative PSA, Gleason score, and angiolymphatic invasion. Kaplan–Meier survival analysis showed that patients with high NUCB2 expression have shorter biochemical recurrence (BCR)-free survival time compared to patients with low NUCB2 expression. Multivariate analysis revealed that NUCB2 expression was an independent predictor of BCR-free survival. Conclusions: NUCB2 might play a positive role in PCa development and could serve as an independent predictor of BCR-free survival.

Nucleobindin 2 (NUCB2) protein, a novel oncoprotein, is overexpressed in breast cancer. To date, there have been no published data regarding the role of NUCB2 protein expression in prostate cancer (PCa). Therefore, this study was performed to investigate the correlations between NUCB2 protein expression and prognosis in patients with PCa.

Background: In reference to previous studies, necroptosis played an important role in cancer development. Our team decided to explore the potential prognostic values of long non-coding RNAs (lncRNAs) associated with necroptosis in bladder urothelial carcinoma (BLCA) and their relationship with the tumor microenvironment (TME) and the immunotherapeutic response for accurate dose.Methods: To obtain the required data, bladder urothelial carcinoma transcriptome data were searched from Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/). We used co-expression analysis, differential expression analysis, and univariate Cox regression to screen out prognostic lncRNAs associated with necroptosis in BLCA. Then the least absolute shrinkage and selection operator (LASSO) was conducted to construct the necroptosis-associated lncRNAs model. Based on this model, we also performed the Kaplan–Meier analysis and time-dependent receiver operating characteristics (ROC) to estimate the prognostic power of risk score. Multivariate and univariate Cox regression analysis were performed to build up a nomogram. Calibration curves, and time-dependent ROC were also conducted to evaluate nomogram. Principal component analysis (PCA) revealed a difference between high- and low-risk groups. In addition, we explored immune analysis, gene set enrichment analyses (GSEA), and evaluation of the half-maximal inhibitory concentration (IC50) in constructed model. Finally, the entire samples were divided into three clusters based on model of necroptosis-associated lncRNAs to further compare immunotherapy in cold and hot tumors.Results: A model was built up based on necroptosis-associated lncRNAs. The model revealed good consistence between calibration plots and prognostic prediction. The area of 1-, 3-, and 5-year OS under the ROC curve (AUC) were 0.707, 0.679, and 0.675. Risk groups could be helpful for systemic therapy due to the markedly diverse IC50 between risk groups. To our delight, clusters could effectively identify cold and hot tumors, which would be beneficial to accurate mediation. Clusters 2 and 3 were considered the hot tumor, which was more sensitive to immunotherapeutic drugs.Conclusions: The outcomes of our study suggested that necroptosis-associated lncRNAs could effectively predict patients with BLCA prognosis, which may be helpful for distinguishing the cold and hot tumors and improving individual treatment of BLCA.

While recent research has shown that expression of RABEX-5 in breast cancer and colorectal cancer has a crucial impact on tumor development, there is little information regarding RABEX-5 expression in prostate cancer. This study investigated the expression of RABEX-5 in prostate cancer by real time quantitative polymerase chain reaction and evaluated its association with clinicopathological variables, including prostate cancer patient prognosis. A total of 180 patients with primary prostate cancer treated by radical prostatectomy were enrolled. Real time quantitative polymerase chain reaction was utilized to investigate mRNA expression level of RABEX-5 in 180 paired prostate cancer/adjacent non-cancerous tissues. RABEX-5 mRNA expression was divided into high expression group and low expression group and correlations between RABEX-5 mRNA and clinicopathological factors were then evaluated. Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the association between RABEX-5 mRNA expression and prognosis of patients with prostate cancer. Our study showed that RABEX-5 mRNA was significantly upregulated in prostate cancer tissues. The data indicated that high expression of RABEX-5 mRNA was significantly associated with lymph node metastasis (P = 0.001), clinical stage (P = 0.004), biochemical recurrence (P = 0.009), preoperative prostate-specific antigen (P < 0.001), and Gleason score (P < 0.001). High RABEX-5 mRNA expression was a significant predictor of poor biochemical recurrence free survival and overall survival both in univariate and multivariate analysis. This is to our knowledge the first report investigating tumor RABEX-5 mRNA expression level in prostate cancer. We have shown that high RABEX-5 mRNA expression is a strong predictor of poor prognosis in prostate cancer patients treated by radical prostatectomy, and multivariate analysis confirmed RABEX-5 mRNA as an independent prognostic factor.