Clear cell renal cell carcinoma (ccRCC) is a major histological subtype of renal cell carcinoma and can be clinically divided into four stages according to the TNM criteria. Identifying clinical stage-related genes is beneficial for improving the early diagnosis and prognosis of ccRCC. By using bioinformatics analysis, we aim to identify clinical stage-relevant genes that are significantly associated with the development of ccRCC. First, we analyzed the gene expression microarray data sets: GSE53757 and GSE73731. We divided these data into five groups by staging information—normal tissue and ccRCC stages I, II, III, and IV—and eventually identified 500 differentially expressed genes (DEGs). To obtain precise stage-relevant genes, we subsequently applied weighted gene coexpression network analysis (WGCNA) to the GSE73731 dataset and KIRC data from The Cancer Genome Atlas (TCGA). Two modules from each dataset were identified to be related to the tumor TNM stage. Several genes with high inner connection inside the modules were considered hub genes. The intersection results between hub genes of key modules and 500 DEGs revealed UBE2C, BUB1B, RRM2, and TPX2 as highly associated with the stage of ccRCC. In addition, the candidate genes were validated at both the RNA expression level and the protein level. Survival analysis also showed that 4 genes were significantly correlated with overall survival. In conclusion, our study affords a deeper understanding of the molecular mechanisms associated with the development of ccRCC and provides potential biomarkers for early diagnosis and individualized treatment for patients at different stages of ccRCC.
AIMS:To determine the predictability of diagnosing diabetic nephropathy (DN) versus non-diabetic renal disease (NDRD) from clinical and laboratory data in Chinese patients with type 2 diabetes mellitus (T2DM) manifesting heavy proteinuria. METHODS:We retrospectively analyzed the clinical and laboratory data of patients with T2DM manifesting heavy proteinuria who underwent renal biopsy from January 2014 to December 2017. RESULTS:According to renal biopsy, 220 patients were finally enrolled, including 109 cases diagnosed with DN alone (49.55%), 94 with NDRD alone (42.73%) and 17 with DN plus superimposed NDRD (7.73%). Multivariate analysis showed the significant risk factors for DN alone were age, duration of diabetes, presence of retinopathy, 24-h proteinuria, serum albumin and SBP. Presence of retinopathy achieved the highest overall diagnostic efficiency with the area under the curve of 0.852, sensitivity of 78.9% and specificity of 91.5%. The combined diagnosis with four indicators (duration of diabetes, retinopathy, SBP, and serum albumin) showed the area under the curve of 0.938, sensitivity of 88.1% and specificity of 87.2%. CONCLUSIONS:The prevalence of DN is high in patients with T2DM manifesting heavy proteinuria. Renal biopsy should be performed in diabetics in the atypical clinical scenario.
The incidence of Kaposi's sarcoma (KS) is increasing among renal transplant recipients. Patients with end‐stage renal disease (ESRD) are immunocompromised and are candidates for renal transplantation, but HHV8 seroprevalence in ESRD patients has not been well documented. A cross‐sectional study of 286 ESRD patients and 281 matched subjects without kidney disease was conducted at the First People's Hospital of Huzhou, Zhejiang province to explore the epidemiologic features of HHV8 among ESRD patients in China. Blood samples were collected and HHV8 antibodies and serologic indices were measured. The seroprevalence of HHV8 was 15.3% for ESRD patients and 8.9% for the comparison group. A significant difference in the geometric mean titer (GMT) of the HHV8 antibodies was detected between ESRD patients and the comparison group (617.1 vs 291.7; P = 0.042). The average level of hemoglobin was 11.56 ± 1.78 g/dL for the ESRD group and 13.73 ± 1.42 g/dL for the comparison group, (P > 0.05). Multiple linear regression revealed a negative association between HHV8 infection and plasma hemoglobin concentration (β = −0.682, P = 0.036). We found a higher HHV8 prevalence and a higher level of HHV8 antibody GMT in ESRD patients than the comparison group, which indicate a high risk of posttransplantation KS.
PURPOSE:To identify altered pathways in an individual with clear cell renal cell carcinoma (ccRCC) using accumulated normal sample data.METHODS:Gene expression data of E-GEOD-40435 was downloaded from the ArrayExpress database. Gene-level statistics of genes in tumor and normal samples were computed. Then, the Average Z method was applied to calculate the individual pathway aberrance score (iPAS). Subsequently, the significantly altered pathways in a ccRCC sample were identified using T-test based on the pathway statistics values of normal and ccRCC samples. Moreover, the identified altered pathways were verified through two methods: one was assessing classification capability for microarray data samples, and the other was computing the changed percentage of each pathway in ccRCC samples.RESULTS:Based on the threshold, 886 altered pathways were identified in all samples. The most significant pathways were potassium transport channels, proton-coupled monocarboxylate transport, beta oxidation of octanoyl-CoA to hexanoyl-CoA, antigen presentation: folding, assembly and peptide loading of class I MHC, and so on. Additionally, iPAS separated ccRCC from normal controls with an accuracy of 0.980. Moreover, a total of 5 significant pathways with change in 100% ccRCC samples were extracted including proton-coupled monocarboxylate transport, antigen presentation: folding, assembly and peptide loading of class I MHC, and so on.CONCLUSIONS:iPAS is useful to predict marker pathways for ccRCC with a high accuracy. Pathways of proton-coupled monocarboxylate transport, and antigen presentation: folding, assembly and peptide loading of class I MHC might play crucial roles in ccRCC progression.
Atherosclerosis is the most common cause of cardiovascular morbidity in end-stage renal disease (ESRD) patients and carotid intima–media thickness (IMT) is an early independent predictor of atherosclerosis. The aim of this study is to compare the continuous ambulatory peritoneal dialysis (CAPD) and the maintenance hemodialysis (MHD) for carotid IMT in Chinese ESRD patients. A total of 72 CAPD patients, 92 MHD patients, and 50 age- and sex-matched healthy controls were included. Dialysis patients were divided into five subgroups according to dialysis duration: 3–6, 7–12, 13–59, 60–119, and 120–179 months. Carotid IMT and carotid plaques were detected for each patient. The carotid IMT and total plaque detection rate in the CAPD and MHD groups were considerably higher than in the healthy control group (p < 0.01). No significant difference was found in the carotid IMT and total plaque detection rate between the CAPD group and the MHD group (p > 0.05). However, after stratification by dialysis duration, the total carotid IMT in the CAPD subgroup was higher than in the MHD subgroup in dialysis duration of 60–119 and 120–179 months (p < 0.05), and there was no significant difference in the total plaque detection rate between the CAPD and MHD subgroups in the same dialysis duration (p > 0.05). Our study showed that both CAPD and MHD affect carotid IMT in Chinese ESRD patients, and the degree of atherosclerosis in CAPD patients might be higher than that in MHD patients after 5 years of dialysis.