FAM64A is an androgen receptor-regulated feedback tumor promoter in prostate cancer.

Endocrine therapy for prostate cancer (PCa) mainly inhibits androgen receptor (AR) signaling, due to increased androgen synthesis and AR changes, PCa evolved into castration-resistant prostate cancer (CRPC). The function of Family With Sequence Similarity 64 Member A (FAM64A) and its association with prostate cancer has not been reported. In our research, we first reported that FAM64A is up-regulated and positively associated with poor prognosis of patients with prostate cancer (PCa) by TCGA database and immunohistochemistry staining. Moreover, knockdown of FAM64A significantly suppressed the proliferation, migration, invasion, and cell cycle of PCa cells in vitro. Mechanistically, FAM64A expression was increased by dihydrotestosterone (DHT) through direct binding of AR to FAM64A promoter, and notably promoted the proliferation, migration, invasion, and cell cycle of androgen-dependent cell line of PCa. In addition, abnormal expression of FAM64A affects the immune and interferon signaling pathway of PCa cells. In conclusion, FAM64A was up-regulated by AR through directly binding to its specific promoter region to promote the development of PCa, and was associated with the immune mechanism and interferon signaling pathway, which provided a better understanding and a new potential for treating PCa.

TCEAL2 as a Tumor Suppressor in Renal Cell Carcinoma is Associated with the Good Prognosis of Patients.

BACKGROUND: Renal cell carcinoma (RCC) is one of the most common tumors in urinary tract tumors. However, the mechanism that supports renal cell carcinoma is unclear. The function of transcription elongation factor A (SII)-like 2 (TCEAL2) and its association with human cancer have not been reported. MATERIALS AND METHODS: To explore the role of TCEAL2 in carcinogenesis of clear cell renal cell carcinoma (ccRCC), we performed bioinformatics analysis to determine the expression levels of TCEAL2 in ccRCC specimens and normal kidney tissue and then verified findings with our samples by qPCR, Western blot and immunohistochemistry staining. Furthermore, the lentiviral vectors were used to increase the expression of TCEAL2 in ccRCC cell lines. The immunofluorescence assay was taken to observe the subcellular location of TCEAL2 in ccRCC cells, and CCK-8 and flow cytometry were introduced for assessing cell proliferation and cell cycle of ccRCC cells, respectively. RESULTS: Compared with adjacent normal kidney tissue and human proximal tubular epithelial cells, the expression of TCEAL2 in ccRCC tissues and cell lines was down-regulated. Patients who had low expression of TCEAL2 had a statistically significant late tumor stage. Restore of TCEAL2 in ccRCC cells inhibited cell proliferation and induced cell cycle arrest in S phase of ccRCC cells. CONCLUSION: To our knowledge, this is the first report of TCEAL2 expression changes in ccRCC. We found that the decrease of TCEAL2 expression may be related to the occurrence of ccRCC. Further research is needed to clarify the molecular mechanism of TCEAL2 in progress of ccRCC.

Systematic analysis of survival-associated alternative splicing signatures in clear cell renal cell carcinoma.

Alternative splicing (AS) constitutes a major reason for messenger RNA (mRNA) and protein diversity. Increasing studies have shown a link to splicing dysfunction associated with malignant neoplasia. Systematic analysis of AS events in kidney cancer remains poorly reported. Therefore, we generated AS profiles in 533 kidney renal clear cell carcinoma (KIRC) patients in The Cancer Genome Atlas (TCGA) database using RNA-seq data. Then, prognostic models were developed in a primary cohort (N = 351) and validated in a validation cohort (N = 182). In addition, splicing networks were built by integrating bioinformatics analyses. A total of 11 268 and 8083 AS variants were significantly associated with patient overall survival time in the primary and validation KIRC cohorts, respectively, including STAT1, DAZAP1, IDS, NUDT7, and KLHDC4. The AS events in the primary KIRC cohorts served as candidate AS events to screen the independent risk factors associated with survival in the primary cohort and to develop prognostic models. The area under the curve of the receiver-operator characteristic curve for prognostic prediction in the primary and validation KIRC cohorts was 0.84 and 0.82 at 2500 days of overall survival, respectively. In addition, splicing correlation networks revealed key splicing factors (SFs) in KIRC, such as HNRNPH1, HNRNPU, KHDBS1, KHDBS3, SRSF9, RBMX, SFQ, SRP54, HNRNPA0, and SRSF6. In this study, we analyzed the AS landscape in the TCGA KIRC cohort and detected predictors (prognostic) based on AS variants with high performance for risk stratification of the KIRC cohort and revealed key SFs in splicing networks, which could act as underlying mechanisms.

NDNF inhibits the migration and invasion of human renal cancer cells through epithelial-mesenchymal transition.

Neuron-derived neurotrophic factor (NDNF) is a glycosylated, disulfide-bonded secretory protein that contains a fibronectin type III domain. NDNF has been identified as a neurotrophic factor; however, its role in carcinogenesis has not yet been identified. To investigate the expression and role of NDNF in carcinogenesis, the expression of NDNF in human Renal cell carcinoma (RCC) cell lines and tissues was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Cell proliferation was investigated using CCK-8 and colony formation assays, and the cell invasion and immigration capacity was evaluated using the transwell assay. The results demonstrated that NDNF expression was downregulated in RCC cell lines and RCC tissues. Restoring NDNF expression significantly inhibited the proliferation, migration and invasion of RCC cells. The study also demonstrated that the inhibitory effect of NDNF on invasive ability was mediated by suppressing the epithelial-mesenchymal transition (EMT) in RCC cells. NDNF may therefore be considered an important regulator of EMT in RCC progression and may represent a novel promising target for antimetastatic therapy.

miR-216b Post-Transcriptionally Downregulates Oncogene KRAS and Inhibits Cell Proliferation and Invasion in Clear Cell Renal Cell Carcinoma.

BACKGROUND/AIMS: Increasing evidence has shown that miR-216b plays an important role in human cancer progression. However, little is known about the function of miR-216b in renal cell carcinoma. METHODS: The expression levels of miR-216b in renal cell carcinoma tissues and cell lines were examined by qRT-PCR. The biological role of miR-216b in renal cell carcinoma proliferation and/or metastasis was examined in vitro and in vivo. The target of miR-216b was identified by a dual-luciferase reporter assay. The expression level of KRAS protein was measured by western blotting. RESULTS: The expression of miR-216b was downregulated in clear cell renal cell carcinoma (ccRCC) cell lines and specimens compared to the adjacent normal tissues. Furthermore, miR-216b can bind to the 3'untranslated region (UTR) of KRAS and inhibit the expression of KRAS through translational repression. The in vitro study revealed that miR-216b attenuated ccRCC cell proliferation and invasion. Furthermore, in vivo study also showed that miR-216b suppressed tumor growth. MiR-216b exerted its tumor suppressor function through inhibiting the KRAS-related MAPK/ERK and PI3K/AKT pathways. CONCLUSION: Our findings provide, for the first time, significant clues regarding the role of miR-216b as a tumor suppressor by targeting KRAS in ccRCC.

Aberrant expression of KPNA2 is associated with a poor prognosis and contributes to OCT4 nuclear transportation in bladder cancer.

Recent studies show that Karyopherin alpha 2 (KPNA2) is up-regulated in quite a number of cancers and associated with poor prognosis. Here, we found that expression levels of KPNA2 and OCT4 are up-regulated in bladder cancer tissues and significantly associated with primary tumor stage and bladder cancer patients' poorer prognosis. Our data also showed decreased cell proliferation and migration rates of bladder cancer cell lines when the expression of KPNA2 and OCT4 was silenced. Meanwhile, cell apoptosis rate was increased. Furthermore, Co-IP and immunofluorescence assay showed the KPNA2 interacts with OCT4 and inhibits OCT4 nuclear transportation when KPNA2 was silenced. Thus, we confirmed that up-regulated KPNA2 and OCT4 expression is a common feature of bladder cancer that is correlated with increased aggressive tumor behavior. Also, we propose that KPNA2 regulates the process of OCT4 nuclear transportation in bladder cancer.

Wilms' tumor in a 51-year-old patient: An extremely rare case and review of the literature.

Wilms tumor or nephroblastoma is a common kidney malignant tumor in childhood, accounting for ~5% of all pediatric tumors. At present, reports on Wilms' tumor occurring in adults, particularly at ages >30 years, are extremely rare. The majority of the cases of adult Wilms' tumor are closely associated with chemotherapy. Furthermore, in rare cases, Wilms' tumor is characterized by three classic types of cells, namely blastemal, stromal and epithelial cells. We herein report a case of Wilms' tumor with three classic types of cells on histological examination in a 51 year-old male patient who had received prior chemotherapy. The patient promptly underwent radical nephrectomy and remains alive. A review of previously presented cases of adult Wilms' tumor from PubMed database was also performed.

Primary adrenal sarcomatoid carcinoma metastatic to the lung: Case report and review of the literature.

Adrenal sarcomatoid carcinoma is a rare adrenal carcinoma. To the best of our knowledge, only 11 cases have been reported since 1987. Adrenal sarcomatoid carcinoma presents a diagnostic challenge due to its atypical symptoms and histological patterns. At the time of diagnosis, a large percentage of patients are already at the metastatic stage and succumb within a few months. The present study reports a case of a 59-year-old man presenting with asthenia and weight loss with adrenal sarcomatoid carcinoma metastatic to the lung. A computed tomography (CT) scan and ultrasonography of the patient's abdomen suggested a large homogeneous mass in the right adrenal gland, and a CT scan of his chest suggested lung metastasis. Right adrenalectomy was performed. Histological examination revealed that the tumor was composed of sarcomatous and carcinomatous differentiation elements. Immunohistochemical examination revealed tumor cell positivity for vimentin and cytokeratin. At the 6-month follow-up the patient exhibited no disease progression and refused further proposed treatment. The patient was alive at the time of writing the current report. The present case report additionally reviews the literature, for the purpose of raising awareness of these rare lesions and assisting in achieving accurate diagnoses and effective treatment.

Down-regulation of C12orf59 is associated with a poor prognosis and VHL mutations in renal cell carcinoma.

C12orf59 is newly identified gene in kidney. However, the relation of C12orf59 expression and clinic features is unknown. Here, our study showed that C12orf59 was broadly expressed in normal human tissues with high expression levels in kidney while its expression is beyond detectable in a panel of cancer cell lines. C12orf59 expression in RCC was significantly decreased compared with corresponding adjacent noncancerous tissues (P < 0.01). The decreased C12orf59 expression was correlated with lymph node status (P < 0.05), distant metastases (P < 0.05), poor survival (P < 0.001) (HR 3.00; 95% CI, 1.29-7.53), VHL non-sense mutations or frame-shift mutations (P < 0.01), and UMPP gene non-sense mutations or frame-shift mutations (P = 0.01). Thus, we propose that the decreased C12orf59 expression status is a prognostic biomarker of ccRCC and cooperates with the loss of VHL all the while promoting renal carcinogenesis.

MicroRNA-451a is associated with cell proliferation, migration and apoptosis in renal cell carcinoma.

MicroRNAs (miRNAs) are an important class of small, non­coding RNA molecules that regulate gene expression at the transcriptional or post­transcriptional level. They are involved in apoptosis, proliferation and migration and are known to have an important role in many types of cancer. Aberrant expression of miRNA­451a (miR­451a) has previously been reported in tumors, however its role in renal cell carcinoma (RCC) is currently unknown. The aim of the present study was to investigate the role of miR­451a in RCC. The expression of miR­451a was analyzed in 50 paired RCC and normal tissues by quantitative polymerase chain reaction. Furthermore, the effects of miR­451a on cell migration, proliferation and apoptosis were evaluated, using migration scratch, MTT and flow cytometric assays. The present study demonstrated that miR­451a was upregulated in RCC, as compared with paired normal tissues (P<0.05). Downregulation of miR­451a using a synthesized inhibitor, significantly suppressed cell migration and proliferation, and induced apoptosis of renal cancer cells in vitro, as compared with a negative control (P<0.05). In the present study, it was determined that miR­451a may have an important role as a tumor enhancer in RCC. These results imply that miR­451a may be a promising therapeutic target for the treatment of RCC.

Global gene expression profiling identifies ALDH2, CCNE1 and SMAD3 as potential prognostic markers in upper tract urothelial carcinoma.

BACKGROUND: Current knowledge about the molecular properties and prognostic markers of upper tract urothelial carcinoma (UTUC) is sparse and often based on bladder urothelial carcinoma (UC), which is thought to share common risk factors with UTUC. However, studies have suggested that differences exist regarding tumor behavior and molecular biology of these cancers, comprehensive investigations are needed to guide the clinical management of UTUC. In recent years, massively parallel sequencing has allowed insights into the biology of many cancers, and molecular prognostic markers based on this approach are rapidly emerging. The goal of this study was to characterize the gene expression patterns of UTUC using massively parallel sequencing, and identify potential molecular markers for prognosis in patients with UTUC. METHODS: We compared the genome-wide mRNA expression profile of cancer and matched normal tissues from 10 patients with UTUC to identify significantly deregulated genes. We also examined the protein levels of prognostic marker candidates in 103 patients with UTUC, and tested the association of these markers with overall survival using Kaplan-Meier model and Cox regression. RESULTS: Functional enrichment of significantly deregulated genes revealed that expression patterns of UTUC were characterized by disorders of cell proliferation and metabolism. And we also compared the expression profile of UTUC with that of bladder UC. Our results highlighted both shared (e.g. disorders of cell cycling and growth signal transduction) and tumor-specific (e.g. abnormal metabolism in UTUC and disruptions of adhesion pathways in bladder UC) features of these two cancers. Importantly, we identified that low protein expression of ALDH2 while high CCNE1 and SMAD3 were significantly associated with increased depth (*P <0.05) and lower overall survival (***P <0.0001) in an independent set of 103 patients. Multivariate Cox regression revealed that all these three genes were independent prognostic indicators in patients with UTUC (***P <0.001). CONCLUSIONS: In conclusion, our study characterized the comprehensive expression profile of UTUC and highlighted both commons and differences in expression patterns between UTUC and bladder UC. And we, for the first time, revealed that ALDH2, CCNE1 and SMAD3 are associated with prognosis in patients with UTUC.

Mixed adenocarcinoma, sarcomatoid carcinoma and adenosquamous carcinoma of the prostate: A case report.

Adenosquamous carcinoma (ASC) and sarcomatoid carcinoma (SC) of the prostate are rare, but highly aggressive tumors. The occurrence of mixed carcinomas in the prostate is even more rarely reported. The present study reports the case of a 62-year-old male who was diagnosed with prostatic adenocarcinoma accompanied by multiple bone metastases, as shown by a needle biopsy and skeletal computed tomography scan. The patient was treated with hormonal therapy, but thereafter, specimens from a transurethral resection of the prostate (TURP) were found to be composed of three histologically distinct elements: ASC, SC and adenocarcinoma. The level of p53 was evaluated by immunohistochemistry in detail, and it was found that this was significantly increased in the TURP samples compared with the needle biopsy samples. The abnormal level of p53 was likely associated with the prognosis of the patient; the patient succumbed to prostate carcinoma two months after the confirmation of the diagnosis.

CMTM3 inhibits human testicular cancer cell growth through inducing cell-cycle arrest and apoptosis.

Human CMTM3 has been proposed as a putative tumor suppressor gene. The loss of CMTM3 has been found in several carcinomas. However, the regulation of CMTM3 expression and its function in tumor progression remain largely unknown. Here, we investigated the regulation of CMTM3 expression, function and molecular mechanism in human testicular cancer cells. CMTM3 was frequently downregulated or silenced in testicular cancer cell lines and tumor tissues but highly expressed in normal testis tissues. The re-expression of CMTM3 significantly suppressed the colony formation, proliferation, and migration capacity of testicular cancer cells by inducing a G2 cell cycle arrest and apoptosis. Moreover, the re-expression of CMTM3 activated the transcription of p53, induced p53 accumulation, up-regulated the expression of p21, and increased the cleavage of caspase 9, 8, 3, and PARP. The downregulation of CMTM3 in clinical tumor tissues was associated with the methylation of a single CpG site located within the Sp1/Sp3-responsive region of the core promoter. These results indicate that CMTM3 can function as tumor suppressor through the induction of a G2 cell cycle arrest and apoptosis. CMTM3 is thus involved in testicular cancer pathogenesis, and it is frequently at least partially silenced by the methylation of a single, specific CpG site in tumor tissues.

Telomerase reverse transcriptase gene promoter mutations help discern the origin of urogenital tumors: a genomic and molecular study.

Activation of telomerase can be observed in almost all human tumor histotypes and detection of the urinary telomerase activities is useful for the diagnosis and surveillance of bladder cancer. In this study, we screened, by Sanger sequencing, 302 patients with various urogenital cancers for somatic mutations in the promoter of the telomerase reverse transcriptase (TERT) gene and determined the clinical relevance of TERT promoter mutations in urogenital cancer. In vitro assays were also performed to evaluate the functional influence of the discovered mutations. We found that the frequencies of somatic mutations in the TERT promoter varied substantially between different types of urogenital tumors (range: 0-63.7%), with urothelial carcinomas showing the highest mutation frequency and prostate cancer showing no mutation. The mutations upregulated the expression of TERT and enhanced the invasiveness of the tumor cells. The mutations were more prevalent in older patients with invasive diseases and advanced tumor stages, and were associated with significantly shorter survival time. Moreover, we also observed a significant co-occurrence of mutations between the TERT promoter and the tumor protein 51/retinoblastoma1 (TP53/RB1) signaling pathway. Hence, TERT promoter mutations may serve as important markers for the differential diagnosis and surveillance of urogenital tumors.

Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation.

Bladder cancer is one of the most common cancers worldwide, with transitional cell carcinoma (TCC) being the predominant form. Here we report a genomic analysis of TCC by both whole-genome and whole-exome sequencing of 99 individuals with TCC. Beyond confirming recurrent mutations in genes previously identified as being mutated in TCC, we identified additional altered genes and pathways that were implicated in TCC. Notably, we discovered frequent alterations in STAG2 and ESPL1, two genes involved in the sister chromatid cohesion and segregation (SCCS) process. Furthermore, we also detected a recurrent fusion involving FGFR3 and TACC3, another component of SCCS, by transcriptome sequencing of 42 DNA-sequenced tumors. Overall, 32 of the 99 tumors (32%) harbored genetic alterations in the SCCS process. Our analysis provides evidence that genetic alterations affecting the SCCS process may be involved in bladder tumorigenesis and identifies a new therapeutic possibility for bladder cancer.

Renal plasmacytoma: Report of a rare case and review of the literature.

Renal plasmacytoma is extremely rare, presenting diagnostic challenges due to its unusual location and non-specific or absent symptoms. To the best of our knowledge, only 24 cases of renal plasmacytoma have been reported in the literature. The present study reports a case of primary renal plasmacytoma in a 46-year-old female patient. Computed tomography (CT) revealed that the mass was located in the lower pole of the left kidney and metastasis was detected in an enlarged para-aortic lymph node. Following careful preparation, a partial nephrectomy was performed and the retroperitoneal lymph node was resected. A pathological examination revealed a renal parenchyma with lymph node involvement; this was confirmed by immunohistochemistry and nested polymerase chain reaction (PCR). Consequently, a diagnosis of a renal extramedullary plasmacytoma (EMP) was proposed. Following this unexpected diagnosis, various examinations were performed, but there was no evidence of systemic plasma cell disease. The patient refused further therapy, including external beam radiotherapy and chemotherapy. Abdominal CT was performed three months post-surgery and did not reveal any relapse. The patient remains disease-free at nine months post-surgery. The current study also presents a review of the literature. Although the general prognosis and outcome of EMP is good, a follow-up examination is recommended due to the possibility of relapse or progression to plasma cell neoplasm (PCN).

Identification of miR-7 as an oncogene in renal cell carcinoma.

MicroRNA-7 (miR-7) has been described as a tumor suppressor in several human cancers, but the results of a study to identify miRNAs associated with metastatic capability in breast cancer suggested that miR-7 may be characterized as an oncogene. The present study was to determine the expression and function of miR-7 in renal cell carcinoma. Quantitative real-time polymerase chain reaction was used to validate the expressions of miR-7 in 48 paired renal cell carcinomas (RCC) and normal tissues, based on the preliminary sequencing results of miRNAs. Furthermore, the impacts of miR-7 on cell migration, proliferation and apoptosis were analyzed using wound scratch assay, MTT and flow cytometry, respectively. The results demonstrated that miR-7 was up-regulated in RCC compared with normal tissues (p = 0.001). Down-regulation of miR-7 with synthesized inhibitor inhibited cell migration in vitro, suppressed cell proliferation and induced renal cancer cell apoptosis, prompting that miR-7 could be characterized as an oncogene in RCC. The present study was the first to reveal that miR-7 was up-regulated in RCC and it played an important role in RCC by affecting cellular migration, proliferation and apoptosis. Further researches should be conducted to explore the roles and target genes of miR-7 in RCC and other cancers.

Increased expression of pregnancy up-regulated non-ubiquitous calmodulin kinase is associated with poor prognosis in clear cell renal cell carcinoma.

PURPOSE: The aims of this study were to evaluate the clinical significance and potential prognostic value of pregnancy up-regulated non-ubiquitous calmodulin kinase (PNCK) in clear cell renal cell carcinoma (ccRCC) patients. MATERIALS AND METHODS: The expression of PNCK mRNA was determined in 24 paired samples of ccRCCs and adjacent normal tissues using real-time RT-PCR. The expression of PNCK was determined in 248 samples of ccRCCs and 92 paired samples of adjacent normal tissues by immunohistochemical analysis. Statistical analysis was performed to define the relationship between PNCK expression and the clinical features of ccRCC. RESULTS: The mRNA level of PNCK was significantly higher in tumorous tissues than in the adjacent non-tumorous tissues (p<0.001). An immunohistochemical analysis of 92 paired tissue specimens showed that PNCK expression was higher in tumorous tissues than in the adjacent non-tumorous tissues (p<0.001). Moreover, there was a significant correlation between the PNCK expression and various clinicopathological parameters such as Fuhrman grade (p = 0.011), tumor size (p<0.001), T stage (p<0.001) and N stage (p = 0.015). Patients with higher PNCK expression had shorter overall survival time than those with lower PNCK expression (p<0.001). Multivariate analysis indicated that PNCK expression was an independent predictor for poor survival of ccRCC patients. CONCLUSIONS: To our knowledge, this is the first study that determines the relationship between PNCK and prognosis in ccRCC. We found that increased PNCK expression is associated with poor prognosis in ccRCC. PNCK may represent a novel prognostic marker for ccRCC.

TGF-ß-activated kinase-1: a potential prognostic marker for clear cell renal cell carcinoma.

BACKGROUND: TGF-ß-activated kinase-1 (TAK1) has been found to be over-expressed in a variety of solid malignancies and related to tumor growth. The aim of this study was to evaluate the expression level of TAK1 in clear cell renal cell carcinoma (ccRCC) and assess its value as a novel prognostic marker. METHODS: TAK1 mRNA was assessed in 51 paired ccRCC tissues and adjacent normal tissues (ADTs) by real-time PCR. Tissue TAK1 protein was also assessed in 91 ADTs and 177 samples of ccRCC immunohistochemically for evaluation of relationships with clinical characteristics. RESULTS: RT-PCR showed that TAK1 RNA level was significantly higher in ccRCC tissues than in the paired ADTs and immunohistochemistry confirmed higher expression of TAK1 protein in ccRCC samples compared with ADTs. TAK1 protein expression in 177 ccRCC samples was significantly correlated with T stage, N classification, metastasis, recurrence and Fuhrman grade, but not age and gender. Patients with low TAK1 levels had a better survival outcome. TAK1 expression and N stage were independent prognosis factors for the overall survival of ccRCC patients. CONCLUSIONS: Overexpression of TAK1 predicts a poor prognosis in patients with ccRCC, so that TAK1 may serve as a novel prognostic marker.

High expression of FER tyrosine kinase predicts poor prognosis in clear cell renal cell carcinoma.

FER tyrosine kinase (FER) has been demonstrated to play a critical role in tumorigenesis and metastasis; however, its potential value as a novel prognostic marker for clear cell renal cell carcinoma (ccRCC) remains unclear. In 48 paired samples of ccRCCs and normal adjacent tissues (ADTs), real-time PCR was used to evaluate the expression of FER mRNA. The expression of FER protein was assessed in 87 ADTs and 206 samples of ccRCC using immunohistochemical methods. Statistical analysis was used to examine the correlations between the expression levels of FER and the clinical characteristics of ccRCC patients. A significant difference was identified between ccRCC tissues and ADTs in the mRNA levels of FER. Immunohistochemistry analyses revealed higher expression of FER protein in 87 ccRCC samples compared to the paired ADTs. In addition, FER protein expression in 206 ccRCC samples was significantly correlated with tumor size, T stage, N classification, metastasis, recurrence and Fuhrman grade, while associations with age and gender were not identifed. The Kaplan-Meier survival analysis showed that patients with high FER levels had a poorer survival outcome compared with those with lower levels. The log-rank test demonstrated that the cumulative survival rates were significantly different between the two groups. The Cox regression analysis indicated that FER expression, N stage and distant metastasis were independent prognostic factors for overall survival of ccRCC patients. Our results indicate that overexpression of FER in tumor tissues predicts a poor prognosis of patients with ccRCC, and FER may serve as a novel prognostic marker for ccRCC.