Kidney cancer is one of the most common urological cancers worldwide, and kidney renal clear cell cancer (KIRC) is the major histologic subtype. Our previous study found that von-Hippel Lindau (VHL) gene mutation, the dominant reason for sporadic KIRC and hereditary kidney cancer-VHL syndrome, could affect VHL disease-related cancers development by inducing telomere shortening. However, the prognosis role of telomere-related genes in kidney cancer has not been well discussed. In this study, we obtained the telomere-related genes (TRGs) from TelNet. We obtained the clinical information and TRGs expression status of kidney cancer patients in The Cancer Genome Atlas (TCGA) database, The International Cancer Genome Consortium (ICGC) database, and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. Totally 353 TRGs were differential between tumor and normal tissues in the TCGA-KIRC dataset. The total TCGA cohort was divided into discovery and validation TCGA cohorts and then using univariate cox regression, lasso regression, and multivariate cox regression method to conduct data analysis sequentially, ten TRGs (ISG15, RFC2, TRIM15, NEK6, PRKCQ, ATP1A1, ELOVL3, TUBB2B, PLCL1, NR1H3) risk model had been constructed finally. The kidney patients in the high TRGs risk group represented a worse outcome in the discovery TCGA cohort (p<0.001), and the result was validated by these four cohorts (validation TCGA cohort, total TCGA cohort, ICGC cohort, and CPTAC cohort). In addition, the TRGs risk score is an independent risk factor for kidney cancer in all these five cohorts. And the high TRGs risk group correlated with worse immune subtypes and higher tumor mutation burden in cancer tissues. In addition, the high TRGs risk group might benefit from receiving immune checkpoint inhibitors and targeted therapy agents. Moreover, the proteins NEK6, RF2, and ISG15 were upregulated in tumors both at the RNA and protein levels, while PLCL1 and PRKCQ were downregulated. The other five genes may display the contrary expression status at the RNA and protein levels. In conclusion, we have constructed a telomere-related genes risk model for predicting the outcomes of kidney cancer patients, and the model may be helpful in selecting treatment agents for kidney cancer patients.

Metastasis is the primary cause of death in renal cell carcinoma (RCC). Loss of cell-to-cell adhesion, including tight junctions (TJs) is the initial step in the process of metastasis. Claudin-7 (CLDN7) is a major component of TJs. However, the clinical significance and its regulation of kidney tumorigenesis remain poorly understood. A total of 120 fresh clear cell RCC (ccRCC) specimens and 144 primary RCC and adjacent nonmalignant renal paraffin specimens were obtained from Department of Urology, Peking University First Hospital. Expression of CLDN7 in ccRCC tissues and cell lines were determined using bioinformatic data mining, quantitative real-time PCR (qRT-PCR), Western blotting and immunostaining. The clinical significance of CLDN7 expression and promoter DNA methylation status was analyzed in ccRCC patients from Peking University First Hospital and The Cancer Genome Atlas. Additionally, the methylation specific-PCR, bisulfite genomic sequencing and demethylation analysis of CLDN7 were performed. Biological functions of CLDN7 were investigated by examining cell proliferation using MTS assays and EdU incorporation assays, cell migration by in vitro wound healing assays and transwell migration assays, cell invasion by transwell invasion assays, and cell apoptosis by flow cytometry. Mouse model experiments were performed to confirm the effects of CLDN7 on tumor growth and metastasis in vivo. The molecular mechanism of CLDN7 function was investigated using gene-set enrichment analysis (GSEA) and high-throughput cDNA sequencing (RNA-Seq) and confirmed by qRT-PCR, Western blot and immunostaining in vitro and in vivo. Our findings revealed that CLDN7 is frequently downregulated via hypermethylation of its promoter in ccRCC. CLDN7 can help predict aggressive tumor status and poor prognosis in ccRCC patients. Interestingly, hypermethylation of the CLDN7 promoter was related to advanced ccRCC status and poor prognosis. Moreover, overexpression of CLDN7 induced cell apoptosis, suppressed proliferation, migration and invasion abilities of ccRCC cells both in vitro and in vivo. Additionally, GSEA and RNA-Seq results showed that CLDN7 had negative effects in cancer-associated signaling pathways and (epithelial-mesenchymal transition) EMT-related pathways. These results were validated by qRT-PCR, Western blot and immunostaining. We have demonstrated a previously undescribed role of CLDN7 as a ccRCC suppressor and suggest that loss of CLDN7 potentiates EMT and tumor progression. CLDN7 may serve as a functional tumor suppressor in tumor progression and a potential biomarker and target in patients with ccRCC.

Purpose: The present study aimed to establish a hypoxia related genes model to predict the prognosis of kidney clear cell carcinoma (KIRC) patients using data accessed from The Cancer Genome Atlas (TCGA) database and International Cancer Genome Consortium (ICGC) database.Methods: Patients’ data were downloaded from the TCGA and ICGC databases, and hypoxia related genes were accessed from the Molecular Signatures Database. The differentially expressed genes were evaluated and then the differential expressions hypoxia genes were screened. The TCGA cohort was randomly divided into a discovery TCGA cohort and a validation TCGA cohort. The discovery TCGA cohort was used for constructing the hypoxia genes risk model through Lasso regression, univariate and multivariate Cox regression analysis. Receiver operating characteristic (ROC) curves were used to assess the reliability and sensitivity of our model. Then, we established a nomogram to predict the probable one-, three-, and five-year overall survival rates. Lastly, the Tumor Immune Dysfunction and Exclusion (TIDE) score of patients was calculated.Results: We established a six hypoxia-related gene prognostic model of KIRC patients in the TCGA database and validated in the ICGC database. The patients with high riskscore present poorer prognosis than those with low riskscore in the three TCGA cohorts and ICGC cohort. ROC curves show our six-gene model with a robust predictive capability in these four cohorts. In addition, we constructed a nomogram for KIRC patients in the TCGA database. Finally, the high risk-group had a high TIDE score than the patients with low riskscore.Conclusions: We established a six hypoxia-related gene risk model for independent prediction of the prognosis of KIRC patients was established and constructed a robust nomogram. The different riskscores might be a biomarker for immunotherapy strategy.

The aim of the study is to evaluate the role of cytoreductive nephrectomy (CN) with thrombectomy before targeted molecular therapy (TMT) on survival in metastatic renal cell carcinoma (mRCC) with venous tumor thrombus. We performed a retrospective analysis of 47 patients treated in our center from April 2008 to October 2014. In the study, 20 patients underwent CN with thrombectomy followed by targeted therapy (group 1); 15 patients received targeted therapy alone (group 2); and 12 patients underwent CN with thrombectomy alone (group 3). The overall survival (OS) and cancer-specific survival (CSS) were calculated according to the Kaplan-Meier survival curve method, and prognostic variables were assessed by Cox regression analyses. The median follow-up times of group 1, group 2, and group 3 were 24.5, 12, and 6.5 months, respectively. During follow-up, in both group 1 and group 3, 12 patients died. In group 2, 14 patients died. The median OS of group 1, group 2, and group 3 was 22, 12, and 6 months, respectively (P < 0.001). Compared with surgery alone and targeted therapy alone, patients with cytoreductive surgery before targeted therapy had statistically better survival benefits (P < 0.001, P = 0.009, respectively). On univariate analysis, the number of metastatic sites (P = 0.004) was a statistically significant prognostic factor influencing OS. Our single-center experience showed that CN with thrombectomy before targeted therapy improved the survival of patients with mRCC with venous tumor thrombus. The number of metastatic sites was an independent prognostic factor influencing OS.

Introduction: Kidney cancer is one of the most common and lethal urological malignancies. Discovering a biomarker that can predict prognosis and potential drug treatment sensitivity is necessary for managing patients with kidney cancer. SUMOylation is a type of posttranslational modification that could impact many tumor-related pathways through the mediation of SUMOylation substrates. In addition, enzymes that participate in the process of SUMOylation can also influence tumorigenesis and development.Methods: We analyzed the clinical and molecular data which were obtanied from three databases, The Cancer Genome Atlas (TCGA), the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC), and ArrayExpress.Results: Through analysis of differentially expressed RNA based on the total TCGA-KIRC cohort, it was found that 29 SUMOylation genes were abnormally expressed, of which 17 genes were upregulated and 12 genes were downregulated in kidney cancer tissues. A SUMOylation risk model was built based on the discovery TCGA cohort and then validated successfully in the validation TCGA cohort, total TCGA cohort, CPTAC cohort, and E-TMAB-1980 cohort. Furthermore, the SUMOylation risk score was analyzed as an independent risk factor in all five cohorts, and a nomogram was constructed. Tumor tissues in different SUMOylation risk groups showed different immune statuses and varying sensitivity to the targeted drug treatment.Discussion: In conclusion, we examined the RNA expression status of SUMOylation genes in kidney cancer tissues and developed and validated a prognostic model for predicting kidney cancer outcomes using three databases and five cohorts. Furthermore, the SUMOylation model can serve as a biomarker for selecting appropriate therapeutic drugs for kidney cancer patients based on their RNA expression.

Birt–Hogg–Dubé (BHD) syndrome, a hereditary renal cancer syndrome caused by mutations in the folliculin (FLCN) gene, is characterized by the presence of fibrofolliculomas, pulmonary cysts, spontaneous pneumothorax, and renal cell carcinoma (RCC). Few BHD syndrome cases have been reported in Asian countries, and cutaneous presentations are relatively rare in Asian patients. Asian BHD patients may be misdiagnosed due to their atypical manifestations. Here, we report two Chinese BHD patients with novel FLCN mutations (c.946-947delAG in exon 9 and c.770-772delCCT in exon 7). Both of them had RCC and spontaneous pneumothorax without fibrofolliculomas. In patients with RCC and pulmonary cysts but without cutaneous lesions, screening for mutations in the FLCN gene should be performed, especially for those with a family history of RCC or pulmonary cysts (pneumothorax).