Comprehensive analysis of glutathione peroxidase-1 (GPX1) expression and prognostic value in three different types of renal cell carcinoma

BackgroundGlutathione peroxidase-1 (GPX1) is generally expressed in tissues with high oxygen tension such as the kidneys and lungs, and its main function is to degrade reactive oxygen species (ROS) and protect cells from oxidative stress. Studies have shown that GPX1 is upregulated in many tumor tissues and is closely related to tumor progression and metastasis. This study aimed to explore the possibility of GPX1 as a biomarker for kidney chromophobe cell carcinoma (KICH), kidney renal papillary cell carcinoma (KIRP), and kidney renal clear cell carcinoma (KIRC).MethodsThe Oncomine and GEPIA databases were used to analyze the GPX1 expression differences between tumor and normal tissues, and the UALCAN, GEPIA and DriverDBv3 databases were used to perform the survival analyses. The GeneMANIA interactive tool was then used to find the GPX1-related protein-protein interaction (PPI). Following this, the LinkedOmics database was used for the enrichment analysis of GPX1, and the Timer database was used to estimate the abundance of immune infiltration. Finally, quantitative polymerase chain reaction (qPCR) was performed on patient specimens collected in the clinic to confirm the database findings.ResultsIn our study, we found that the expression of GPX1 in three types of renal cell carcinoma (RCC) were upregulated, and the high expression of GXP1 was related to the poor prognosis of patients with KICH and KIRC. On the contrary, KIRP patients with a high expression of GPX1 had a better prognosis. In addition, GPX1 was related to the abundance of immune cell infiltration. The results of the qPCR analysis confirmed that the expression of GPX1 in RCC was increased compared with the control group (P<0.05).ConclusionsOur results indicate that the expression of GPX1 is related to the prognosis of three types of RCC. As such, GPX1 expression could be a reliable diagnostic and prognostic biomarker for RCC and, more importantly, may provide a new direction for therapeutic strategies.     

Potential upstream lncRNA–miRNA–mRNA regulatory network of the ferroptosis-related gene SLC7A11 in renal cell carcinoma

BackgroundSLC7A11 is a key regulator of ferroptosis, which mediates cysteine uptake for glutathione biosynthesis and maintains redox homeostasis. Emerging evidence has shown that SLC7A11 is upregulated in many human tumors. Nevertheless, the prognosis and posttranslational regulatory mechanism of SLC7A11 in renal cell carcinoma (RCC) remains obscure.MethodsThe Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), and The Cancer Genome Atlas (TCGA) databases were used to analyze the difference in SLC7A11 expression between malignant and normal tissues. Furthermore, the GEPIA, the University of ALabama at Birmingham CANcer data analysis Portal (UALCAN), and starBase databases were used to conduct the survival analyses. For correlation analysis, the UALCAN and starBase databases were employed. The Tumor Immune Estimation Resource (TIMER) database was used to approximate the abundance of immune infiltration.ResultsWe confirmed that SLC7A11 was upregulated in most human cancers, including 3 types of RCC. SLC7A11 overexpression was linked to poor prognosis of individuals with kidney renal clear cell carcinoma (KIRC), kidney chromophobe cell carcinoma (KICH), and kidney renal papillary cell carcinoma (KIRP). SLC7A11 expression was also linked to immune cell infiltration levels. After performing a comprehensive analysis of the regulatory mechanisms of SLC7A11 expression, the results depicted a potential noncoding (ncRNA)–messenger RNA (mRNA) axis, incorporating SNHG6–miR-26a-5p–SLC7A11 networks in KICH, CASC19/CYTOR/LINC00997–miR-27b–3pSLC7A11 networks in KIRC, and CASC19/CYTOR/PVT1–miR27b-3p–SLC7A11 networks in KIRP as partially responsible for the functions of SLC7A11 in RCC. SLC7A11 expression was positively linked to infiltrated immune cells and their matching marker sets in 3 types of RCC, including CD8⁺ and myeloid dendritic cells.ConclusionsOur research elucidated the crucial functions and the upstream long noncoding RNA (lncRNA)–microRNA (miRNA) regulatory network of SLC7A11 in RCC. Importantly, SLC7A11 can be used as a potential prognostic biomarker for 3 types of RCC and to determine the infiltration of immune cells in malignant tissues.     

Cystic renal cell carcinoma,suspected because of lack of regression of renal cysts after renal transplantation in a dialysis patient with acquired renal cystic disease

A 34-year-old man who had been on dialysis for about 6 years, and had acquired renal cystic disease, received a renal transplantation. However, in spite of the success of the transplantation, one area without cyst regression was observed in the original kidney. Therefore, carcinoma was suspected and nephrectomy was performed. Histology revealed cystic renal cell carcinoma (RCC). No case of cystic RCC occurring in a dialysis patient has previously been reported. Cystic RCC should be suspected in a cystic mass in the original kidney which does not regress after successful renal transplantation. Received: August 23, 2002 / Accepted: November 25, 2002 Acknowledgments We thank Dr. Shigehiko Sato, Department of Internal Medicine, Tonami General Hospital, who referred this patient to us. Correspondence to:I. Ishikawa     

The predictive accuracy of preoperative erythrocyte count and maximum tumor diameter to maximum kidney diameter ratio in renal cell carcinoma

BackgroundThe purpose of this study was to investigate the predictive accuracy of erythrocyte count and maximum tumor diameter to maximum kidney diameter ratio (TKR) in patients with renal cell carcinoma (RCC).MethodsWe retrospectively analyzed the clinicopathological epidemiological characteristics of patients with RCC in the First Hospital of Shanxi Medical University from 2010 to 2014. Among them, 295 cases with complete follow-up data at the time of visit were selected. We collected data including erythrocyte counts and length of each diameter line of the tumor and kidney. To predict the prognosis of RCC, receiver operating characteristic (ROC) curve analysis was used to calculate the cutoff value of each parameter.ResultsOf the 295 included patients, 199 (67.5%) were male, 96 (32.5%) were female, and the mean (± SD) age was 56.45±11.03 years. The area under the curve (AUC) of the erythrocyte count and the TKR for predicting the prognosis of RCC were 0.672 (SD 0.031; P<0.001) and 0.800 (SD 0.030; P<0.001), respectively. When the cutoff value of the erythrocyte count and TKR count were 3.975 and 0.452, the highest Youden index values were 0.309 and 0.685, and the corresponding sensitivity and specificity were 0.826 and 0.685, and 0.483 and 1.000, respectively.ConclusionsAn erythrocyte count <3.975×10¹²/L and a TKR >0.452 were found to be risk factors for poor prognosis in patients with RCC.     

The Clinicopathologic and Molecular Landscape of Clear Cell Papillary Renal Cell Carcinoma: Implications in Diagnosis and Management

BackgroundClear cell papillary renal cell carcinoma (CCPRCC) is a recently described tumor entity. Several questions remain about its epidemiology, molecular features, and clinical behavior.ObjectiveTo comprehensively evaluate clinicopathologic and molecular features of CCPRCC, and compare it with more common kidney cancer subtypes.Design, setting, and participantsWe identified 89 CCPRCC patients and compared their clinicopathologic features with 1120 localized clear cell renal cell carcinoma (ccRCC) and 129 type 1 papillary renal cell carcinoma (pRCC) patients.Outcome measurements and statistical analysisNonparametric statistical testing was used to compare relevant features between tumor types. Overall, cancer-specific survival (CSS) and metastasis-free survival estimates were calculated from initial diagnosis using the Kaplan-Meier method. Patients with ipsilateral multifocal disease were explored further. A subset of CCPRCC tumors underwent genomic analysis and were compared with other RCC subtypes.Results and limitationsA higher proportion of female (45% vs 32%) and African-American (19% vs 3%) patients were observed in the CCPRCC cohort than in the ccRCC and pRCC cohorts. CCPRCC tumors also had increased odds of presenting with additional ipsilateral masses (odds ratio [OR]: 4.41 [confidence interval {CI}: 2.34, 8.15], p < 0.001) and bilateral disease (OR: 4.80 [CI: 2.40, 9.59], p < 0.001) compared with ccRCC tumors. On molecular analysis, CCPRCC tumors showed fewer somatic aberrations and a greater degree of mitochondrial DNA depletion. In multifocal CCPRCC tumors, histologic concordance among the different renal cell carcinoma masses was estimated at 44% (7/16), and none of the individuals presenting exclusively with CCPRCC tumors developed metastatic disease after 5 yr. In contrast, multifocal tumors with CCPRCC and other nonconcordant histologies were more likely to experience adverse outcomes (CSS, log rank p = 0.034).ConclusionsCCPRCC is characterized by distinct molecular and epidemiologic features that could be used to refine current diagnostic approaches. Although their clinical course is generally indolent, multifocal CCPRCC tumors represent a unique diagnostic challenge. In this context, single-mass biopsies could miss concomitant aggressive disease, with a potential negative impact on patient outcomes. Furthermore, high discordance rates in multifocal CCPRCC tumors have important clinical implications in management.Patient summaryWe explored the molecular and clinical features of clear cell papillary renal cell carcinoma (CCPRCC) relative to other kidney cancer subtypes. While CCPRCC generally conveys a good prognosis, additional caution should be taken when it is diagnosed using biopsy if multiple kidney masses are present.     

Cystic renal cell carcinoma carries an excellent prognosis regardless of tumor size

IntroductionCystic renal cell carcinoma (cystic RCC) is thought to carry an improved prognosis relative to clear cell RCC (CCRCC); however, this is based on small case series. We used a population-based tumor registry to compare clinicopathologic features and cancer-specific mortality (CSM) of cystic RCC with those of CCRCC.Materials and methodsThe Surveillance, Epidemiology, and End Results database was queried for all patients diagnosed and treated for cystic RCC and CCRCC between 2001 and 2010. Clinical and pathologic factors were compared using t tests and chi-square tests as appropriate. Kaplan-Meier survival analysis compared CSM differences between cystic RCC and CCRCC.ResultsA total of 678 patients with cystic RCC and 46,677 with CCRCC were identified. The mean follow-up duration was 52 and 40 months, respectively. When compared with CCRCC patients, those with cystic RCC were younger (mean age 58 vs. 61 y, P <0.001), more commonly black (22% vs. 9%, P<0.001), and female (45% vs. 41%, P = 0.02). Cystic RCCs were more commonly T1a tumors (66% vs. 55%, P<0.001), well differentiated (33% vs. 16%, P<0.001), and smaller (mean size = 3.8 vs. 4.5 cm, P<0.001). Cystic RCC was associated with a reduction in CSM when compared with CCRCC (P = 0.002). In a subset analysis, this reduction in CSM was seen only for those with T1b/T2 tumors (P = 0.01) but not for those with T1a RCCs lesions (P = 0.31).ConclusionsWe report the largest series of cystic RCC and corroborate the findings of improved CSM when compared with CCRCC for larger tumors; however, no difference was noted in smaller tumors, suggesting that tumor biology becomes more relevant to prognosis with increasing size. These data may suggest a role for active surveillance in appropriately selected patients with small, cystic renal masses.     

Upregulation of matrix metalloproteinase 14 (MMP14) is associated with poor prognosis in renal clear cell carcinoma—a bioinformatics analysis

BackgroundMatrix metalloproteinase 14 (MMP14) has been reported to be upregulated in some types of cancer and to promote cancer cell invasion and metastasis. However, the expression profile and functional role of MMP14 in kidney renal clear cell carcinoma (KIRC) remains unknown. This study investigated the association between MMP14 expression level and prognosis in KIRC.MethodsThe messenger RNA (mRNA) expression profile and clinical data (including T stage, N stage, M stage, pathologic stage, gender, race, age, histologic grade, serum calcium, hemoglobin) were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database. Protein expression was evaluated by immunohistochemistry in the Human Protein Atlas (HPA) database. Correlation analyses between MMP14 and all mRNAs in KIRC were batch calculated, and gene set enrichment analyses (GSEA) were then conducted of Disease Ontology (DO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using R packages. Multivariate logistic regression analysis was used to explore the prognostic factors of KIRC patients.ResultsThe gene expression of MMP14 was significantly upregulated in KIRC tissues when compared with the normal tissue (P<0.001). The predictive ability of MMP14 as a variable for predicting tumor and normal outcomes had certain accuracy based on the receiver operating characteristic (ROC) model [area under the curve (AUC) =0.881, confidence interval (CI): 0.844-0.917]. When compared with the normal kidney tissue, the protein expression of MMP14 in KIRC got an increased trend, but due to the limited sample size, the difference is not statistically significant (P>0.05). Survival analysis revealed that MMP14 was significantly associated with overall survival in KIRC (P=0.013). GSEA of DO terms indicated high expression of MMP14 was related to KIRC, and GSEA of KEGG pathways showed that MMP14 and its coexpressed genes were significantly positively correlated with pathways in cancer. Signaling pathway GSEA indicated the upregulation of MMP14 in KIRC may activate cancer pathways.ConclusionsMMP14 may be associated with poor prognosis in KIRC and may be a potential prognostic marker for KIRC.     

Two-dimensional correlated spectroscopy distinguishes clear cell renal cell carcinoma from other kidney neoplasms and non-cancer kidney

BackgroundRoutinely used clinical scanners, such as computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound (US), are unable to distinguish between aggressive and indolent tumor subtypes in masses localized to the kidney, often leading to surgical overtreatment. The results of the current investigation demonstrate that chemical differences, detected in human kidney biopsies using two-dimensional COrrelated SpectroscopY (2D L-COSY) and evaluated using multivariate statistical analysis, can distinguish these subtypes.MethodsOne hundred and twenty-six biopsy samples from patients with a confirmed enhancing kidney mass on abdominal imaging were analyzed as part of the training set. A further forty-three samples were used for model validation. In patients undergoing radical nephrectomy, biopsies of non-cancer kidney cortical tissue were also collected as a non-cancer control group. Spectroscopy data were analyzed using multivariate statistical analysis, including principal component analysis (PCA) and orthogonal projection to latent structures with discriminant analysis (OPLS-DA), to identify biomarkers in kidney cancer tissue that was also classified using the gold-standard of histopathology.ResultsThe data analysis methodology showed good separation between clear cell renal cell carcinoma (ccRCC) versus non-clear cell RCC (non-ccRCC) and non-cancer cortical tissue from the kidneys of tumor-bearing patients. Variable Importance for the Projection (VIP) values, and OPLS-DA loadings plots were used to identify chemical species that correlated significantly with the histopathological classification. Model validation resulted in the correct classification of 37/43 biopsy samples, which included the correct classification of 15/17 ccRCC biopsies, achieving an overall predictive accuracy of 86%, Those chemical markers with a VIP value >1.2 were further analyzed using univariate statistical analysis. A subgroup analysis of 47 tumor tissues arising from T1 tumors revealed distinct separation between ccRCC and non-ccRCC tissues.ConclusionsThis study provides metabolic insights that could have future diagnostic and/or clinical value. The results of this work demonstrate a clear separation between clear cell and non-ccRCC and non-cancer kidney tissue from tumor-bearing patients. The clinical translation of these results will now require the development of a one-dimensional (1D) magnetic resonance spectroscopy (MRS) protocol, for the kidney, using an in vivo clinical MRI scanner.     

Expression and clinical significance of NUF2 in kidney renal clear cell carcinoma

BackgroundTo explore the expression and clinical significance of the cytokinesis-related gene NUF2 in kidney renal clear cell carcinoma (KIRC).MethodsGene expression profiles of KIRC patients were extracted from The Cancer Genome Atlas (TCGA) database. The differences in NUF2 mRNA expression between patients and controls, as well as the relationship between the clinical characteristics and overall survival of the patients, were analyzed. The expression of NUF2 protein in 83 cancer tissues and para-cancerous tissues was detected to analyze the relationship with clinical characteristics. Gene Set Enrichment Analysis (GSEA) was used to investigate the possible regulatory pathways of the NUF2 in the development of KIRC.ResultsNUF2 mRNA was significantly higher in patients with KIRC, and the prognosis of patients with high expression of NUF2 mRNA was significantly worse than those with low expression, and was related to the AJCC stage, T stage, lymph node metastases, and distant metastases. NUF2 mRNA was an independent prognostic risk factor for KIRC patients. The expression of NUF2 protein was significantly higher in KIRC patients than in paraneoplastic tissues and was markedly associated with the pathological grade. In addition, the high expression of NUF2 was associated with the upregulation of pathways such as homologous recombination and DNA replication.ConclusionsNUF2 may act as an independent prognostic biomarker for predicting the survival of KIRC patients.     

KCNN4 is a potential prognostic marker and critical factor affecting the immune status of the tumor microenvironment in kidney renal clear cell carcinoma

BackgroundThe tumor microenvironment (TME) has emerged as a crucial factor in cancer development and progression. Recent findings have indicated that tumor-infiltrating immune cells (TICs) in the TME may predict cancer prognosis and response to treatment. Herein, we sought to identify critical modulators of the kidney renal clear cell carcinoma (KIRC) TME.MethodsKIRC datasets from The Cancer Genome Atlas (TCGA) were analyzed using the ESTIMATE algorithm to determine the ImmuneScore and StromalScore. By profiling the differentially expressed genes (DEGs) in the ImmuneScore and StromalScore, we finally identified the immune- and stromal-related DEGs of the cases, through which we then performed intersection analysis to determine the immune-related genes (IRGs). Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were used to identify critical IRGs and construct a prognostic model. The CIBERSORT algorithm was used to calculate the relative content of 22 immune cell types. Finally, the datasets from the Gene Expression Omnibus (GEO) database were analyzed to validate results from the above analyses. Experimental validation was used on KIRC tissues by quantitative polymerase chain reaction (qPCR) and western blot.ResultsWe found that the ImmuneScore was negatively correlated with patients’ prognosis. Intersection analysis of the ImmuneScore and StromalScore identified 118 IRGs that were enriched in immune-related functions. Following IRGs screening by Cox and LASSO regression analyses, six genes were identified and used to construct a KIRC prognostic model. Intersection analysis of these six genes and protein-protein interaction (PPI) were performed and obtained the most critical gene: Potassium Calcium-Activated Channel Subfamily N Member 4 (KCNN4). Further analysis showed that KCNN4 expression was higher in tumor samples relative to normal controls, and was negatively correlated with prognosis. CIBERSORT analysis revealed significant correlation between KCNN4 expression and multiple types of TICs, demonstrating that KCNN4 may affect KIRC prognosis by influencing the TME immune status. Ultimately, the GEO datasets and validation experiments confirmed that KCNN4 was highly expressed in tumor tissues compared to the corresponding normal tissues.ConclusionsOur study demonstrated that KCNN4 might be a potential prognostic marker in KIRC, offering a novel therapeutic avenue.     

Molecular Tumour Profiling for Detection of Biomarkers in Renal Cell Tumours

ObjectivesFor renal cell tumours, biomarkers for diagnosis, prognostic evaluation, and therapy management are badly needed. This paper describes the development of new biomarkers for clinical use based on molecular tumour profiling of renal tumours.MethodsHigh-throughput techniques for DNA, RNA, and protein analysis, as well as conventional comparative genomic hybridisation and immunochemistry, were used for complex characterisation of specific subtypes of renal cell tumours. Furthermore, ProteinChip technology was performed on serum samples to identify specific biomarkers useful for detection and monitoring of patients.ResultsOn the basis of the specific genetic pattern of each subtype of renal cell tumours, a genetic test for routine diagnostics was developed. Furthermore, expression profiling resulted in a new tumour marker for clear-cell renal cell carcinoma (RCC): CD70. Specific serum protein profiles of RCC patients were defined by performing protein analysis of serum samples, and serum amyloid A1 (SAA1) was identified as a specific serum marker of clear-cell RCC. Protein analysis of tumour tissue and serum is helpful for selection of patients for therapy and for therapy monitoring.ConclusionsOngoing studies on molecular and cellular biology show that differentiation between RCC subtypes with different prognosis, as well as therapeutic options and response rates, seems possible. Furthermore, on the basis of molecular profiles of tumour tissues and body fluids, development of specific therapies and selection for each individual patient become possible.     

Variants and Variations in Epithelial Renal Cell Tumors in Adults: The Pathologist's Point of View

Context and ObjectivesThe Vancouver consensus conference of the International Society of Urological Pathology provided the foundation for the 2016 World Health Organization (WHO) classification of the renal tumors.The aim of this contribution is to review some of the major changes and additions to tumor variants and variations in the current classification of the renal cell neoplasms in adults.Evidence acquisition and Evidence synthesisSeveral publications report no recurrence or metastasis in patients with multilocular cystic renal cell carcinoma (RCC). Multilocular cystic renal neoplasm of low malignant potential is now the term recommended by the WHO for this lesion.A similar recommendation has been made in the current literature for hybrid oncocytic/chromophobe tumors (ie, oncocytic neoplasia of uncertain malignant potential) and for clear cell papillary renal cell carcinoma (ie, neoplasm of low malignant potential). Some of the latter tumors were referred to as renal angioadenomatous tumors.Papillary RCC has traditionally been subdivided into type 1 and type 2 papillary RCCs. Recent molecular studies suggest that type 2 papillary RCCs may not constitute a single well-defined entity. There are newly recognized epithelial renal tumor entities in the 2016 WHO classification such as succinate dehydrogenase-deficient RCC.Conclusions and Patient summaryThere are some additional variations in the tumor types that are not included in the WHO classification, however, worth knowing, such as clear cell RCC with hemangioblastoma-like features and unclassified RCC with medullary phenotype.     

RET protein expression in papillary renal cell carcinoma

ObjectiveTo examine the role of RET in renal malignancy, in particular papillary renal cell carcinoma (RCC).Materials and methodsA cohort of 111 archival renal samples was used consisting of 94 renal cancers (66 papillary RCC, 18 conventional clear cell carcinoma, 10 chromophobe RCC), 4 benign oncocytomas, and 13 normal kidney tissues. RET protein expression was examined by immunohistochemistry and expression levels were correlated with clinicopathologic and patient survival data.ResultsPositive RET staining was seen in 34/66 (52%) papillary RCCs, 4/10 (40%) chromophobe carcinomas, 4/4 (100%) oncocytomas, and 11/13 (85%) normal kidney samples. All 18 cases of conventional clear cell carcinoma had negative RET staining. RET expression was associated with low Fuhrman nuclear grade.ConclusionsRET protein may be contributing in part to an adaptation of a papillary growth pattern in certain renal malignancies. Given the possible therapeutic benefit of small molecule inhibitors of RET activation, further work needs to be done to highlight the functional relevance of RET protein expression in papillary RCC.     

Assessing the clinical use of clear cell renal cell carcinoma molecular subtypes identified by RNA expression analysis

ObjectivesTo evaluate the clinical use of recently published RNA-based molecular subtyping algorithms. Patients who undergo surgery for clinically localized clear cell renal cell carcinoma can experience very different outcomes, representing a longstanding challenge for the practicing urologist. Two recent publications suggest that molecular subtyping based on the expression of large panels of genes can help clinically localized clear cell renal cell carcinoma prognostication; however, the analyses was not adjusted for routinely collected clinicopathologic indices.Methods and materialsWe obtained level 3 RNA-seq RPKM data and corresponding clinicopathologic features from The Cancer Genome Atlas (TCGA) and assigned patients to the TCGA subtypes as well as to the ccA/ccB subtypes. To determine the prognostic ability of molecular subtyping after adjusting for variables that are collected as routine medical care, we used Cox models and adjusted for the composite Mayo stage, size, grade, and necrosis (SSIGN) score.ResultsBoth the TCGA and the ccA/ccB subtypes are significantly associated with tumor size, category, grade, and presence of necrosis. The association of these subtypes with overall survival is markedly attenuated following adjustment for the composite Mayo SSIGN score.ConclusionsBoth the TCGA and the ccA/ccB subtypes are associated with overall survival after adjusting for the Mayo SSIGN score. However, the effect sizes are similar to what has been reported for single markers, and thus the clinical use and cost-effectiveness of these RNA-based whole-genome signatures are questionable.     

SMARCC1 expression is positively correlated with pathological grade and good prognosis in renal cell carcinoma

BackgroundRenal cell carcinoma (RCC), which is derived from the renal tubular epithelium, is now the most common urological cancer. Of the four RCC subtypes, clear cell RCC (ccRCC) is the most common subtype and accounts for 75–80% of all RCC cases. SMARCC1, also known as BAF155, together with SMARCA4, SMARCA2, and SMARCB1, comprises the SWI/SNF protein family. It has been reported that the expression of SMARCC1 was correlated with some human cancers including prostate cancer, colon cancer, and pancreatic cancer. However, the mechanisms and regulatory roles of SMARCC1 in ccRCC are not well defined.MethodsOur current study primarily investigated the expression of SMARCC1 and its clinical importance in two common histological types of ccRCC using microarrays (HKidE180Su02, MecDNA-HKidE030CS01).ResultsThe results showed that the expression of SMARCC1 in ccRCC tissues was significantly decreased compared with that in corresponding para-tumor tissue (4.370±2.036 vs. 6.167±1.162, P=0.001). SMARCC1 expression was positively correlated with pathological grade (r=0.224, P=0.011). Moreover, ccRCC patients with high SMARCC1 expression had a better prognosis than those with low SMARCC1 expression (40.0% vs. 95.2%, P=0.000) in the following sub-groups: pathological grade (III and IV), male sex (73.5% vs. 95.3%, P=0.004), and tumor size >5 cm (62.5% vs. 89.5%, P=0.044).ConclusionsA further study is necessary to explain the mechanism of the occurrence and progression of ccRCC.     

Features and outcomes of renal cell carcinoma of native kidneys in renal transplant recipients

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To outline the features and outcomes of renal cell carcinoma (RCC) in native kidneys of renal transplant recipients, who are at increased risk of developing this disease.

PATIENTS AND METHODS

We retrospectively studied the clinicopathological features and survival of 28 surgically treated RCCs, which developed in 24 renal transplant recipients. Features and outcomes were compared with 671 patients with RCC who had no renal transplant.

RESULTS

The median interval between renal transplantation and the occurrence of RCC was 5.6 years. Acquired cystic kidney disease was present in 83% of the transplanted patients. Compared with the patients with RCC and no renal transplant, RCCs of native kidneys in transplant recipients were more frequently incidental findings (92% vs 77%, P = 0.092), multifocal (39% vs 15%, P < 0.001), bilateral (17% vs 4%, P = 0.006), had lower T stages (P = 0.040), were smaller (P = 0.027), of lower grades (P = 0.010), were more frequently papillary (43% vs 19%, P = 0.019) and occurred at a significantly younger age (P = 0.022). After a median follow‐up of 6.7 years, eight renal transplant recipients had died (33%), but only two deaths were due to RCC. Survival with metastatic RCC was only 4 months, if a full resection of all metastatic sites was not achieved. In multivariate analysis the presence of a renal transplant had no effect on survival.

CONCLUSIONS

Most RCCs in renal transplant recipients are incidental low‐stage, low‐grade tumours with a favourable prognosis. The outstanding pathological findings are bilateral occurrence, papillary subtype and multifocality. Prognosis of metastatic RCC is poor but might be favourable if all metastases are resected. Screening for early detection of asymptomatic RCC is advocated.