A novel 7-chemokine-genes predictive signature for prognosis and therapeutic response in renal clear cell carcinoma

Background: Renal clear cell carcinoma (ccRCC) is one of the most prevailing type of malignancies, which is affected by chemokines. Chemokines can form a local network to regulate the movement of immune cells and are essential for tumor proliferation and metastasis as well as for the interaction between tumor cells and mesenchymal cells. Establishing a chemokine genes signature to assess prognosis and therapy responsiveness in ccRCC is the goal of this effort.Methods: mRNA sequencing data and clinicopathological data on 526 individuals with ccRCC were gathered from the The Cancer Genome Atlas database for this investigation (263 training group samples and 263 validation group samples). Utilizing the LASSO algorithm in conjunction with univariate Cox analysis, the gene signature was constructed. The Gene Expression Omnibus (GEO) database provided the single cell RNA sequencing (scRNA-seq) data, and the R package “Seurat” was applied to analyze the scRNA-seq data. In addition, the enrichment scores of 28 immune cells in the tumor microenvironment (TME) were calculated using the “ssGSEA” algorithm. In order to develop possible medications for patients with high-risk ccRCC, the “pRRophetic” package is employed.Results: High-risk patients had lower overall survival in this model for predicting prognosis, which was supported by the validation cohort. In both cohorts, it served as an independent prognostic factor. Annotation of the predicted signature’s biological function revealed that it was correlated with immune-related pathways, and the riskscore was positively correlated with immune cell infiltration and several immune checkpoints (ICs), including CD47, PDCD1, TIGIT, and LAG-3, while it was negatively correlated with TNFRSF14. The CXCL2, CXCL12, and CX3CL1 genes of this signature were shown to be significantly expressed in monocytes and cancer cells, according to scRNA-seq analysis. Furthermore, the high expression of CD47 in cancer cells suggested us that this could be a promising immune checkpoint. For patients who had high riskscore, we predicted 12 potential medications.Conclusion: Overall, our findings show that a putative 7-chemokine-gene signature might predict a patient’s prognosis for ccRCC and reflect the disease’s complicated immunological environment. Additionally, it offers suggestions on how to treat ccRCC using precision treatment and focused risk assessment

Is Retzius-sparing robot-assisted radical prostatectomy associated with better functional and oncological outcomes? Literature review and meta-analysis

Objective: To evaluate the efficiency, safety and clinical outcomes of Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) in comparison with the standard RARP. Methods: A systematic search from Web of Science, PubMed, EMBase, Cochrane Library and Google Scholar was performed using the terms “Retzius-sparing”, “Bocciardi approach” and “robot-assisted radical prostatectomy”. Video articles and abstract papers for academic conferences were excluded. Meta-analysis of interested outcomes such as positive surgical margins (PSMs) and continence recovery was undertaken. A comprehensive literature review of all studies regarding Retzius-sparing (RS) approach was conducted and summarized. Results: From 2010 to 2017, 11 original articles about RS-RARP approach were retrieved. Of that, only four studies comparing the RS-RARP approach to the conventional RARP were comparable for meta-analysis. Faster overall continence recovery within 1 month after the surgery was noted in the RS group (61% vs. 43%; p = 0.004). PSMs of pT2 and pT3 stages were not significantly different between the groups (10.0% vs. 7.4%; p = 0.39 and 13.1% vs. 9.5%, p = 0.56, respectively). Of all the studies, only one reported sexual recovery outcomes after RS treatment in which 40% of the participants achieved sexual intercourse within the first month. Conclusion: Though more technically demanding than the conventional RARP, the RS technique is a safe and feasible approach. This meta-analysis and literature review indicates that RS technique, as opposed to the conventional approach, is associated with a faster continence recovery while PSMs were comparable between the two groups. The limitations of observational studies and the small data in our meta-analysis may prevent an ultimate conclusion. Future well-designed RCTs are needed to validate and confirm our findings. Keywords: Retzius-sparing, Radical prostatectomy, Robotics, Functional recovery, Positive surgical margin

DataSheet1_A novel 7-chemokine-genes predictive signature for prognosis and therapeutic response in renal clear cell carcinoma.PDF

Background: Renal clear cell carcinoma (ccRCC) is one of the most prevailing type of malignancies, which is affected by chemokines. Chemokines can form a local network to regulate the movement of immune cells and are essential for tumor proliferation and metastasis as well as for the interaction between tumor cells and mesenchymal cells. Establishing a chemokine genes signature to assess prognosis and therapy responsiveness in ccRCC is the goal of this effort.Methods: mRNA sequencing data and clinicopathological data on 526 individuals with ccRCC were gathered from the The Cancer Genome Atlas database for this investigation (263 training group samples and 263 validation group samples). Utilizing the LASSO algorithm in conjunction with univariate Cox analysis, the gene signature was constructed. The Gene Expression Omnibus (GEO) database provided the single cell RNA sequencing (scRNA-seq) data, and the R package “Seurat” was applied to analyze the scRNA-seq data. In addition, the enrichment scores of 28 immune cells in the tumor microenvironment (TME) were calculated using the “ssGSEA” algorithm. In order to develop possible medications for patients with high-risk ccRCC, the “pRRophetic” package is employed.Results: High-risk patients had lower overall survival in this model for predicting prognosis, which was supported by the validation cohort. In both cohorts, it served as an independent prognostic factor. Annotation of the predicted signature’s biological function revealed that it was correlated with immune-related pathways, and the riskscore was positively correlated with immune cell infiltration and several immune checkpoints (ICs), including CD47, PDCD1, TIGIT, and LAG-3, while it was negatively correlated with TNFRSF14. The CXCL2, CXCL12, and CX3CL1 genes of this signature were shown to be significantly expressed in monocytes and cancer cells, according to scRNA-seq analysis. Furthermore, the high expression of CD47 in cancer cells suggested us that this could be a promising immune checkpoint. For patients who had high riskscore, we predicted 12 potential medications.Conclusion: Overall, our findings show that a putative 7-chemokine-gene signature might predict a patient’s prognosis for ccRCC and reflect the disease’s complicated immunological environment. Additionally, it offers suggestions on how to treat ccRCC using precision treatment and focused risk assessment.</p