Increasing evidences show the clinical significance of the interaction between hypoxia and immune in clear cell renal cell carcinoma (ccRCC) microenvironment. However, reliable prognostic signatures based on a combination of hypoxia and immune have not been well established. Moreover, many studies have only used RNA-seq profiles to screen the prognosis feature of ccRCC. Presently, there is no comprehensive analysis of multiomics data to mine a better one. Thus, we try and get it. First, t-SNE and ssGSEA analysis were used to establish tumor subtypes related to hypoxia-immune, and we investigated the hypoxia-immune–related differences in three types of genetic or epigenetic characteristics (gene expression profiles, somatic mutation, and DNA methylation) by analyzing the multiomics data from The Cancer Genome Atlas (TCGA) portal. Additionally, a four-step strategy based on lasso regression and Cox regression was used to construct a satisfying prognostic model, with average 1-year, 3-year and 5-year areas under the curve (AUCs) equal to 0.806, 0.776 and 0.837. Comparing it with other nine known prognostic biomarkers and clinical prognostic scoring algorithms, the multiomics-based signature performs better. Then, we verified the gene expression differences in two external databases (ICGC and SYSU cohorts). Next, eight hub genes were singled out and seven hub genes were validated as prognostic genes in SYSU cohort. Furthermore, it was indicated high-risk patients have a better response for immunotherapy in immunophenoscore (IPS) analysis and TIDE algorithm. Meanwhile, estimated by GDSC and cMAP database, the high-risk patients showed sensitive responses to six chemotherapy drugs and six candidate small-molecule drugs. In summary, the signature can accurately predict the prognosis of ccRCC and may shed light on the development of novel hypoxia-immune biomarkers and target therapy of ccRCC.

Background Circular RNAs (circRNAs) have been indicated as potentially critical mediators in various types of tumor progression, generally acting as microRNA (miRNA) sponges to regulate downstream gene expression. However, the aberrant expression profile and dysfunction of circRNAs in human clear cell renal cell carcinoma (ccRCC) need to be further investigated. This study mined key prognostic circRNAs and elucidates the potential role and molecular mechanism of circRNAs in regulating the proliferation and metastasis of ccRCC. Methods circCHST15 (hsa_circ_0020303) was identified by mining two circRNA microarrays from the Gene Expression Omnibus database and comparing matched tumor versus adjacent normal epithelial tissue pairs or matched primary versus metastatic tumor tissue pairs. These results were validated by quantitative real-time polymerase chain reaction and agarose gel electrophoresis. We demonstrated the biological effect of circCHST15 in ccRCC both in vitro and in vivo. To test the interaction between circCHST15 and miRNAs, we conducted a number of experiments, including RNA pull down assay, dual-luciferase reporter assay and fluorescence in situ hybridization. Results The expression of circCHST15 was higher in ccRCC tissues compared to healthy adjacent kidney tissue and higher in RCC cell lines compared to normal kidney cell lines. The level of circCHST15 was positively correlated with aggressive clinicopathological characteristics, and circCHST15 served as an independent prognostic indicator for overall survival and progression-free survival in patients with ccRCC after surgical resection. Our in vivo and in vitro data indicate that circCHST15 promotes the proliferation, migration, and invasion of ccRCC cells. Mechanistically, we found that circCHST15 directly interacts with miR-125a-5p and acts as a microRNA sponge to regulate EIF4EBP1 expression. Conclusions We found that sponging of miR-125a-5p to promote EIF4EBP1 expression is the underlying mechanism of hsa_circ_0020303-induced ccRCC progression. This prompts further investigation of circCHST15 as a potential prognostic biomarker and therapeutic target for ccRCC.

Most localized human renal clear cell carcinoma (ccRCC)-related deaths result from cancer recurrence and metastasis. However, the precise molecular mechanisms largely remain unknown. In recent years, an increasing number of long noncoding RNAs (lncRNAs) have been shown to be vital regulators of tumorigenesis. In this study, we characterized a lncRNA DUXAP9 and the upregulation of DUXAP9 was analyzed by quantitative real-time PCR in 112 pairs of localized ccRCC tumor tissues compared with adjacent normal tissues. Kaplan–Meier curves showed that patients of localized ccRCC with high DUXAP9 expression had poorer overall survival (P<0.01) and progression-free survival (P<0.05) than cases with low DUXAP9 expression. Multivariate Cox regression analysis also showed that high DUXAP9 expression was an independent risk factor for poor prognosis in localized ccRCC (p<0.05). DUXAP9 knockdown in renal cancer cells inhibited renal cancer cells proliferation and motility capacities in vitro and reversed epithelial–mesenchymal transition (EMT), whereas overexpression of DUXAP9 promoted renal cancer cells proliferation and motility capacities in vitro and induced EMT. Pull-down, RNA immunoprecipitation and RNA stability assays (involving actinomycin D) showed that DUXAP9 was methylated at N6-adenosine and binds to IGF2BP2, which increases its stability. DUXAP9 activate PI3K/AKT pathway and Snail expression in renal cancer cells. DUXAP9 may be useful as a prognostic marker and/or therapeutic target in localized ccRCC.

Background Active surveillance (AS) with delayed intervention has gained acceptance as a management strategy for small renal masses (SRMs). However, during AS, there is a risk of tumor growth. Thus, we aim to investigate whether tumor growth in patients with SRMs leads to tumor progress. Methods In this study, we enrolled 16,070 patients from the Surveillance, Epidemiology, and End Results database with T1a renal cell carcinoma (RCC) between 2004 and 2017. The 16,070 patients were divided into three groups: 10,526 in the partial nephrectomy (PN) group, 2768 in the local ablation (LA) group, and 2776 in the AS group. Associations of tumor size with all‐cause and cancer‐specific mortality were evaluated using Kaplan–Meier analyses and Cox regression models. Results Four tumor size categories were delineated (≤1, >1–2, >2–3, and > 3–4 cm in diameter), and 10‐year all‐cause and cancer‐specific mortality both significantly increased with increasing tumor size in the PN, LA, and AS groups (all p < 0.05). Tumors were substaged based on diameter: T1aA (≤2 cm) and T1aB (>2–4 cm). All‐cause and cancer‐specific mortality were significantly higher in T1aB tumors than T1aA tumors in each group (hazard ratio = 1.395 and 1.538, respectively; all p < 0.05). Conclusions Tumor growth relates to worse prognosis of T1a RCC, and 2 cm serves as a size threshold that is prognostically relevant for patients with T1a RCC. Because of the lack of accurate predictors of tumor growth rate, AS for patients with SRMs incurs a risk of tumor progression.

Objectives: To investigate the factors associated with systemic infection after percutaneous nephrolithotomy (PCNL) and establish a predictive model to provide theoretical basis for the prevention of systemic inflammatory response syndrome (SIRS) and urosepsis correlate to percutaneous nephrostomy.Methods: Patients received PCNL between January 2016 and December 2020 were retrospectively enrolled. All patients were categorized into groups according to postoperative SIRS and urosepsis status. Single factor analysis and multivariate logistic regression analysis were performed to determine the predictive factors of SIRS and urosepsis after PCNL. The nomograms were generated using the predictors respectively and the discriminative ability of was assessed by analyses of receiver operating characteristic curves (ROC curves).Results: A total of 758 PCNL patients were enrolled in this study, including 97 (12.8%) patients with SIRS and 42 (5.5%) patients with urosepsis. Multivariate logistic regression analysis suggested that there were 5 factors related to SIRS, followed by preoperative neutrophil to lymphocyte ratio (NLR) (odds ratio, OR = 1.721, 95% confidence interval, CI [1.116–2.653], p = 0.014), S.T.O.N.E. score (OR = 1.902, 95% CI [1.473–2.457], p &lt; 0.001), female gender (OR = 2.545, 95% CI [1.563–4.144], p &lt; 0.001), diabetes history (OR = 1.987, 95% CI [1.051–3.755], p = 0.035), positive urine culture (OR = 3.184, 95% CI [1.697–5.974], p &lt; 0.001). And there were four factors related to urosepsis, followed by preoperative NLR (OR = 1.604, 95% CI [1.135–2.266], p = 0.007), S.T.O.N.E. score (OR = 1.455, 95% CI [1.064–1.988], p = 0.019), female gender (OR = 2.08, 95% CI [1.063–4.07], p = 0.032), positive urine culture (OR = 2.827, 95% CI [1.266–6.313], p = 0.011). A nomogram prediction model was established to calculate the cumulative probability of SIRS and urosepsis after PCNL and displayed favorable fitting by Hosmer–Lemeshow test (p = 0.953, p = 0.872). The area under the ROC curve was 0.784 (SIRS) and 0.772 (urosepsis) respectively.Conclusion: Higher preoperative NLR, higher S.T.O.N.E. score, female gender, and positive urine culture are the most significant predictors of SIRS and urosepsis. Diabetes history is the predictor of SIRS. These data will help identify high-risk individuals and facilitate early detection of SIRS and urosepsis post-PCNL.