Prognostic value of systemic immune-inflammation index in non-metastatic clear cell renal cell carcinoma with tumor thrombus.

This study aims to determine the prognostic value of SII for non-metastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). We retrospectively collected and analyzed 328 non-metastatic ccRCC patients with VTT who underwent radical nephrectomy and thrombectomy from 3 tertiary centers in China between 2011 to 2021. Kaplan-Meier analyses and Cox proportional hazard analyses were used to determine its prognostic value for overall survival (OS) and disease free survival (DFS). The Harrell concordance index (C-index), receiver operating characteristic curve (ROC) analysis, and decision curve analysis (DCA) were used to evaluate its role in the improvement of prognostic accuracy of the existing models. Nomogram models containing the SII were then developed and evaluated by R. Patients were divided into low-SII and high-SII groups based on the SII optimal cut-off value 912 calculated by the Youden index in all patients. Higher SII was correlated with more symptoms, longer surgical time, higher WHO/ISUP grade, and longer tumor diameter. Kaplan-Meier analyses revealed significant differences in OS and DFS between two groups. Multivariate analyses revealed that SII was an independent prognostic factor for OS (HR:2.220, p=0.002) and DFS (HR:1.846, p=0.002). Compared with other indicators, SII had a superior accuracy (c-index=0.630 for OS and 0.595 for DFS). It also improved the performance of models for predicting OS and DFS (all p <0.01). Based on the results of LASSO Cox regression analysis, we constructed a nomogram to predict OS and it performed well on both the training cohort (AUC=0.805) and the validation cohort (AUC=0.795). Risk stratification based on nomogram can distinguish patients with different risks (all p <0.001). Preoperative SII is an independent predictive factor for OS and DFS of non-metastatic ccRCC patients with VTT. It can be used to improve the performance of current risk models.

Retrospective comparison of clinical outcomes of robotic-assisted laparoscopic partial nephrectomy through transabdominal or retroperitoneal approaches in patients with T1b renal tumor.

BACKGROUND: We compared the intraoperative and postoperative outcomes of robotic-assisted laparoscopic partial nephrectomy (RALPN) via transabdominal or retroperitoneal approaches in patients with stage T1b renal cell carcinoma. METHODS: The medical records for 92 patients who underwent RALPN were retrospectively collected and data on their baseline demographics, duration of operation, duration of renal artery clamping, intraoperative blood loss, recovery time of intestinal functions, surgical margin positive rate, as well as postoperative complications were analyzed. RESULTS: Of the 92 enrolled patients, 43 and 49 patients were subjected to RALPN via the transabdominal and retroperitoneal approaches, respectively. All patients successfully completed the operation. Baseline characteristics for the transabdominal and retroperitoneal groups were comparable. Differences in operative time, renal artery clamping time, intraoperative blood loss, positive rate of surgical margin, and incidences of postoperative complications between the two approaches were insignificant. The recovery time of intestinal function after operation was significantly shorter in patients subjected to the retroperitoneal approach, relative to those subjected to transabdominal approach (p < 0.001). CONCLUSIONS: Application of RALPN via transabdominal or retroperitoneal approaches showed comparable clinical outcomes in patients with stage T1b renal cell carcinoma. The retroperitoneal approach was superior to the transabdominal approach in terms of postoperative intestinal function recovery.

Screening of Differentially Expressed Iron Death-Related Genes and the Construction of Prognosis Model in Patients with Renal Clear Cell Carcinoma.

Objective: In this study, we used the TCGA database and ICGC database to establish a prognostic model of iron death associated with renal cell carcinoma, which can provide predictive value for the identification of iron death-related genes and clinical treatment of renal clear cell carcinoma. Methods: The gene expression profiles and clinical data of renal clear cell carcinoma and normal tissues were obtained in the TCGA database and ICGC database, and the differential genes related to iron death were screened out. The differential genes were screened out by single and multifactor Cox risk regression model. R software, "edge" package (version 4.0), was used to identify the DELs of 551 transcriptional gene samples and 522 clinical samples. The risk prediction model with genes was established to analyze the correlation between the genes in the established model and clinical characteristics, Through the final screening of iron death related genes, it can be used to predict the prognosis of renal clear cell carcinoma and provide advice for clinical targeted therapy. Results: Seven iron death differential genes (CLS2, FANCD2, PHKG2, ACSL3, ATP5MC3, CISD1, PEBP1) associated with renal clear cell carcinoma were finally screened and were refer to previous relevant studies. These genes are closely related to iron death and have great value for the prognosis of renal clear cell carcinoma. Conclusion: Seven iron death genes can accurately predict the survival of patients with renal clear cell carcinoma.

KCNN4 may weaken anti-tumor immune response via raising Tregs and diminishing resting mast cells in clear cell renal cell carcinoma.

BACKGROUND: Studies over the past decade have shown that competitive endogenous RNA (ceRNA) plays an essential role in the tumorigenesis and progression of clear cell renal cell carcinoma (ccRCC). Meanwhile, immune checkpoint blocker is gradually moving towards the first-line treatment of ccRCC. Hence, it's urgent to develop a new prediction model for the efficiency of immunotherapy. At present, there is no study to reveal the effect of ceRNA network on the efficiency of immunotherapy for ccRCC. METHODS: To systematically analyze the effect of ceRNA hub genes in ccRCCon immune response, we constructed prognosis models based on ceRNAs and immune cells, respectively. We constructed ceRNA network using hypergeometric distribution test and correlation analysis with R script based on The Cancer Genome Atlas (TCGA) database. We then applied the Cibersort algorithm to simulate the infiltration overview of immune cells in kidney renal clear carcinoma (KIRC) samples. Prognosis-related immune cells were screened and a predictive model of these cells was constructed. Prognosis-related immune cells and ceRNA hub genes were performed with co-expression analysis. Finally, qRT-PCR and immunofluorescence assays were performed to validate the results. RESULTS: The construction of ceRNA related prognosis model contained 8 hub genes, including RELT, MYO9B, KCNN4, SIX1, OTOGL, MALAT1, hsa-miR-130b-3p, and hsa-miR-21-5p. The area under the receiver operating characteristic curve (AUC) was 0.77 at 5 years. For the construction of immune cells prognosis model, 3 immune cells (T cells regulatory, Macrophages, Mast cells resting) were adopted, and the AUC was 0.65 at 5 years. We then merged the two models by correlation analysis and co-expression analysis. Finally, we found that KCNN4 positively correlates with T cells regulatory (Tregs) and negatively correlates with mast cells resting significantly. Furthermore, higher expression of KCNN4 may lead to a higher potential for immune evasion and lower efficiency for immune checkpoint inhibitors (ICIs). CONCLUSIONS: Generally, this is the first study to assess the prognostic value of immune related ceRNA hub genes in ccRCC, and KCNN4 was finally demonstrated to be a key regulatory factor with strong correlation with Tregs and mast cells resting.

Incidence, Clinical Characteristics, and Survival of Collecting Duct Carcinoma of the Kidney: A Population-Based Study.

OBJECTIVE: To investigate the exact age-adjusted incidence (AAI), clinical characteristics, and survival data of collecting duct carcinoma of the kidney (CDCK) recorded in the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. METHODS: Patients with CDCK confirmed by microscopic examination from 2004 to 2018 were selected from the SEER database. AAI rates were calculated using SEER*Stat software (version 8.3.9). The Kaplan-Meier method was used to evaluate cancer-specific survival (CSS) rates according to tumor size, tumor stage, and treatment methods, and differences among these variables were assessed by the log-rank test. Cox regression analysis was employed to identify variables independently related to CSS. RESULTS: A total of 286 patients with CDCK were identified from the database. The majority of the patients were white (69.2%), male (67.5%), and married (60.5%), and the median age was 59 years. Most patients with CDCK (74.4%) presented with stages III or IV disease. The diameter of most (59.4%) tumors was less than 7 cm, and the tumors were more commonly found on the left than on the right (55.2% vs. 44.8%). The incidence of CDCK decreased over time. The median CSS time was 17 months. In terms of the treatment modalities used, 83.9% of the patients underwent surgery; 32.9% underwent chemotherapy, and 13.6% underwent radiotherapy. The CSS rates at 1, 2, and 5 years were 57.3%, 43.2%, and 30.7%, respectively. In patients with stage IV CDCK treated with surgery alone, chemotherapy alone, and surgery plus chemotherapy, the median survival time was 5 months, 9 months, and 14 months, respectively (P =0.024). Multivariate Cox regression analysis showed surgery, chemotherapy, stage, regional lymph node metastasis, and distant metastasis were independent prognostic factors for patients with CDCK. CONCLUSIONS: CDCK is an uncommon malignant renal carcinoma, and its incidence is decreasing based on the analysis of current data. CDCK is a high stage, regional lymph-nodes positive, and metastatic disease. Compared with surgery alone or chemotherapy alone, patients with stage IV could gain survival benefit from surgery combined with chemotherapy.