Low expression of fatty acid oxidation related gene ACADM indicates poor prognosis of renal clear cell carcinoma and is related to tumor immune infltration

This research aims to identify the key fatty acid beta-oxidation(FAO)genes that are altered in kidney renal clear cell carcinoma(KIRC)and to analyze the role of these genes in KIRC The Gene Expression Omnibus(GEO)and FAO datasets were used to identify these key genes.Wilcoxon rank sum test was used to assess the levels of acyl-CoA dehydrogenase medium chain(ACADM)between KIRC and non cancer samples.The logistic regression and Wilcoxon rank sum test were used to explore the association between ACADM and clinical features.The diagnostic performance of ACADM for KIRC was asessed using a diagnostic receiver operating ch aracteristic(ROC)curve.The co-expressed genes of ACADM were identifed in LinkedOmics database,and their function and pathway enrichment were analyzed.The correlation between ACADM expression level and immune infitration was analyzed by Gene Set Variation Analysis(GSVA)method Additionally,the proliferation,migration,and invasion abilities of KIRC cells were assessed after overexpressing ACADM.Following differential analysis and intersection,we identifed six hub genes,induding ACADM.We found that the expression level of ACADM was decreased in KIRC tissues and had a better diagnostic efect(AUC=0.916).Survival analysis suggested that patients with decreased ACADM expression had a worse prognosis.According to correlation analysis,a variety of dinical features were associated with the expression level of ACADML By analyzing the infiltration level of immune cells,we found that ACADM may be related to the enrichment of immune cells.Finally,ACADM overexpression inhibited proliferation,migration,and invasion of KIRC cells.In conclusion,our findings suggest that reduced ACADM expression in KIRC patients is indicative of poor prognosis.These results imply that ACADM may be a diagnostic and prognostic marker for individuals with KIRC,offering a reference for dinicians in diagnosis and treatment.

Endobronchial metastasis secondary to renal clear cell carcinoma:A case report

BACKGROUND Endobronchial metastases(EBMs)are tumours that metastasise from a malignant tumour outside the lungs to the central and subsegmental bronchi,and are visible under a bronchofibrescope.Most EBMs are formed by direct invasion or metastasis of intrathoracic malignant tumours,such as lung cancer,oesophageal cancer or mediastinum tumours.Renal cell carcinoma(RCC),accounting for 2%to 3%of all tumours,is a common malignant tumour of the urinary system.Renal clear cell carcinoma(RCCC)constitutes the predominant pathological subtype of RCC,comprising approximately 70%to 80%of all RCC cases.RCCC can spread and metastasise through arterial,venous and lymphatic circulation to almost all organs of the body.Moreover,lung,bone,liver,brain and local recurrence are the most common metastatic neoplasms of RCCC.However,EBM from RCCC has a low complication rate and is often misdiagnosed as primary lung cancer.CASE SUMMARY A 71-year-old male patient who had undergone radical left nephrectomy 7 years prior due to RCCC was referred to our hospital due to a 1-mo history of productive cough.The results of an enhanced chest CT scan indicated the presence of a soft tissue nodule in the upper lobe of the left lung,and flexible bronchoscopy revealed a hypervascular lesion in the bronchus of the left lung's superior lobe.Therefore,the patient underwent thoracoscopic left superior lobe wedge resection,and pathology confirmed EBM from the RCCC.CONCLUSION EBM from RCCC has a low incidence and no characteristic clinical manifestations in the early stage.If a bronchial tumour is found in a patient with RCCC,the possibility of bronchial metastatic cancer should be considered.

Incidental renal cell carcinoma post bilateral nephrectomy in autosomal dominant polycystic kidney disease

BACKGROUND Renal cell carcinoma(RCC)is more common in patients with autosomal dominant polycystic kidney disease(ADPKD)than in the general population.Diagnosing RCC in ADPKD is challenging due to the presence of multiple renal cysts,often leading to delays and difficulties in distinguishing RCC from cyst infection or hemorrhage.A total of 38 kidneys were excised from 19 patients,with a mean age of 56.8 years and an average hemodialysis duration of 84.2 months.Eight patients underwent open nephrectomies,and 11 underwent hand-assisted laparoscopic nephrec-tomies.RCC was detected in 15.8%of kidneys,affecting 21.1%of patients.Two patients had multifocal RCC in both kidneys.All RCC cases were pT1 stage,with the largest lesion averaging 16.5 mm in diameter.The average operative duration was 120 minutes,with intraoperative blood loss averaging 184.2 mL.Five patients required blood transfusions.Postoperative complications occurred in five patients,with a mean hospital stay of 17.1 days.The mean follow-up period was 28.1 months.CONCLUSION The prevalence of RCC is higher in patients with ADPKD with ESRD than in those with ESRD alone.Thus,clinicians should be cautious and implement surveillance programs to monitor the development of RCC in patients with ADPKD,particularly those on dialysis.

Network pharmacology and molecular docking analysis reveal insights into the molecular mechanism of Gualou Qumai Wan in clear cell renal cell carcinoma

Background:To initially clarify the potential therapeutic targets and pharmacological mechanism regarding Gualou Qumai Wan(GQW),a kind of traditional Chinese medicine(TCM),in clear cell renal cell carcinoma(ccRCC)by virtue of the network pharmacology analysis and molecular docking analysis.Methods:The screening of bioactive components and targets of GQW was based on the Traditional Chinese Medicine System Pharmacology(TCMSP)and the UniProt platform served for standardizing their targets.Online Mendelian Inheritance in Man(OMIM),PharmGkb,TTD,DrugBank and GeneCards databases were searched to collect the disease targets of ccRCC.Cytoscape assisted in constructing herb-compound-target(H-C-T)networks.The STRING database was searched for constructing the target protein-protein interaction(PPI)networks,while the R programming language served for analyzing GO functional terms and the KEGG pathways related to potential targets.Analyses of core genes related to survival and tumor microenvironment(TME)were conducted respectively based on the GEPIA2 database and TIMER 2.0 database.Human Protein Atlas(HPA)and The Cancer Genome Atlas(TCGA)helped to obtain core genes’protein expression as well as transcriptome expression level.Autodock Vina software validated the molecular docking regarding GQW components and pivotal targets.Results:The constructed H-C-T networks mainly had 33 compounds and 65 targets.A topological analysis of the PPI network identified that ESR1,AKT1,HIF1A,PTGS2,TP53 and VEGFA serve as core targets in the way GQW affects ccRCC.According to the GO and KEGG pathway enrichment analyses,the effects of GQW are mediated by genes related to hypoxia and oxidative stress as well as the Chemical carcinogenesis-receptor activation and PI3K-Akt signaling pathways.AKT1 shows a close relation to the recruitment of various immune cells and can remarkably affect disease prognosis according to reports.Molecular docking and molecular dynamics simulations showed that diosgenin has higher affinity with core targets.Conclusion:The study makes a comprehensive explanation of the biological activity,potential targets,as well as molecular mechanism regarding GQW against ccRCC,which promisingly assists in revealing the action mechanism of TCM formulae in disease treatment and the respective and scientific basis.

Solute carrier-related signature for assessing prognosis and immunity in patients with clear-cell renal cell carcinoma

Background:Clear-cell renal cell carcinoma(ccRCC)is the most common malignant kidney cancer.However,the tumor microenvironment and crosstalk involved in metabolic reprogramming in ccRCC are not well-understood.Methods:We used The Cancer Genome Atlas to obtain ccRCC transcriptome data and clinical information.The EMTAB-1980 cohort was used for external validation.The GENECARDS database contains the first 100 solute carrier(SLC)-related genes.The predictive value of SLC-related genes for ccRCC prognosis and treatment was assessed using univariate Cox regression analysis.An SLC-related predictive signature was developed through Lasso regression analysis and used to determine the risk profiles of patients with ccRCC.Patients in each cohort were separated into high-and low-risk groups based on their risk scores.The clinical importance of the signature was assessed through survival,immune microenvironment,drug sensitivity,and nomogram analyses using R software.Results:SLC25A23,SLC25A42,SLC5A1,SLC3A1,SLC25A37,SLC5A6,SLCO5A1,and SCP2 comprised the signatures of the eight SLCrelated genes.Patients with ccRCC were separated into high-and low-risk groups based on the risk value in the training and validation cohorts;the high-risk group had a significantly worse prognosis(p<0.001).The risk score was an independent predictive indicator of ccRCC in the two cohorts according to univariate and multivariate Cox regression(p<0.05).Analysis of the immune microenvironment showed that immune cell infiltration and immune checkpoint gene expression differed between the two groups(p<0.05).Drug sensitivity analysis showed that compared to the low-risk group,the high-risk group was more sensitive to sunitinib,nilotinib,JNK-inhibitor-VIII,dasatinib,bosutinib,and bortezomib(p<0.001).Survival analysis and receiver operating characteristic curves were validated using the E-MTAB-1980 cohort.Conclusions:SLC-related genes have predictive relevance in ccRCC and play roles in the immunological milieu.Our results provide insight into metabolic reprogramming in ccRCC and identify promising treatment targets for ccRCC.

Pembrolizumab combined with axitinib in the treatment of skin metastasis of renal clear cell carcinoma to nasal ala:A case report

BACKGROUND Renal clear cell carcinoma(RCC)is a malignant tumor of the genitourinary system with a predilection for males.The most common metastatic sites are the lung,liver,lymph nodes,contralateral kidney or adrenal gland,however,skin metastasis has only been seen in 1.0%-3.3%of cases.The most common site of skin metastasis is the scalp,and metastasis to the nasal ala region is rare.CASE SUMMARY A 55-year-old man with clear cell carcinoma of the left kidney was treated with pembrolizumab and axitinib for half a year after surgery and was found to have a red mass on his right nasal ala for 3 mo.The skin lesion of the patient grew rapidly to the size of 2.0 cm×2.0 cm×1.2 cm after discontinuation of targeted drug therapy due to the coronavirus disease 2019 epidemic.The patient was finally diagnosed with skin metastasis of RCC in our hospital.The patient refused to undergo surgical resection and the tumor shrank rapidly after resuming target therapy for 2 wk.CONCLUSION It is rare for an RCC to metastasize to the skin of the nasal ala region.The tumor size change of this patient before and after treatment with targeted drugs shows the effectiveness of combination therapy for skin metastasis.

Aryl hydrocarbon receptor nuclear translocator 2 as a prognostic biomarker and immunotherapeutic indicator for clear cell renal cell carcinoma

Background:In many cancer types,aryl hydrocarbon receptor nuclear translocator 2(ARNT2)has been found to be associated with tumor cell proliferation and prognosis.However,the role of ARNT2 in clear cell renal cell carcinoma(ccRCC)has not been completely elucidated.In this study,the potential role of ARNT2 in ccRCC development was characterized.Methods:A pan-cancer dataset(TCGA-TARGET-GTEx)was accessed from UCSC Xena Data Browser.ARNT2 expression in normal and tumor samples was compared.Univariate Cox regression was performed to evaluate the prognostic value of ARNT2.Single sample gene set enrichment analysis(ssGSEA)was used to estimate the enrichment of functional pathways and gene signatures.CIBERSORT and ESTIMATE methods evaluated the immune infiltration.The ARNT2 expression was determined in ccRCC tissue and cell lines using RT-qPCR and Western blot.Results:ARNT2 expression was significantly dysregulated in 23 out of 30 cancer types.Pan-cancer data revealed a strong correlation between ARNT2 expression and immune modulators,immune cell infiltration,and genomic alternations.In ccRCC patients,the low-ARNT2 expression group had higher immune infiltration,CD8 T cells,and programmed cell death ligand 1 expression,as well as higher enrichment score of immunotherapeutic predictors than those in the high-ARNT2 expression group.Low-ARNT2 expression group was more responsive to immunotherapy.Moreover,low ARNT2 expression was observed in ccRCC tissue and cell lines.Conclusions:Dysregulated ARNT2 expression is involved in cancer development and the modulation of the immune microenvironment.ARNT2 can be potentially used as a prognostic indicator and an immunotherapeutic indicator for ccRCC.

Iris metastasis from clear cell renal cell carcinoma: A case report

BACKGROUND Clear cell renal cell carcinoma(ccRCC)is a common type of tumor that can metastasize to any organs and sites.However,it is extremely rare for ccRCC to metastasize to the iris.Here,we describe a rare case of iris metastasis from ccRCC with a history of left nephrectomy in 2010.CASE SUMMARY A 62-year-old male was admitted to the hospital due to blurred vision and red eyes,and a mass was found on the iris in the right eye.B-scan ultrasonography revealed a well-bounded high-density lesion at the corner of the anterior chamber at the 3-4 o’clock position.Phacoemulsification with simultaneous intraocular lens implantation and iridocyclectomy was performed in the right eye.The lesion was confirmed to be metastatic ccRCC by histological and immunohistochemical analyses.The patient was still alive at 9 mo after surgical treatment.Ocular metastasis can be an initial sign with a poor prognosis.Timely detection and treatment may improve survival.Clinicians should pay attention to similar metastatic diseases to prevent misdiagnosis leading to missed treatment oppor-tunities.CONCLUSION This report of the characteristics and successful management of a rare case of iris metastasis from ccRCC highlights the importance of a comprehensive medical history,histopathology,immunohistochemistry,and clinical manifestation for successful disease diagnosis.

Correlation between Hypovitaminosis D Status and Hyperactivation of IL-6/STAT3 Signaling in Clear Cell Renal Cell Carcinoma

Objective:To analyze serum vitamin D levels in patients with clear cell renal cell carcinoma(ccRCC)by flow cytometry and to investigate the relationship between hypovitaminosis D status and hyperactivation of IL-6/STAT3 signaling in ccRCC.Methods:Eighty patients diagnosed with ccRCC by our oncology department from January 2019 to December 2021 were selected as study subjects,and the control subjects were selected from patients who were receiving health check-up from our hospital(matched according to case group:control group,1:2),with 160 healthy patients.All serum samples collected from the case-control subjects were allowed to stand for 1–2 hours,centrifuged at 3000 rpm for 10 minutes,and stored in a-80°C refrigerator,from which they were removed and thawed to measure 25-hydroxyvitamin D(25(OH)D)and interleukin 6(IL-6)levels.Results:The blood calcium level of patients in the cancer group was significantly lower than that of patients in the non-cancer group,and the difference was statistically significant(P<0.05).The IL-6 level of the cancer group was significantly higher than that of the non-cancer group.In high vitamin D state,the IL-6 level of the non-cancer group was higher than that of the cancer group,and the average concentration of IL-6 in both the cancer group and the non-cancer group was significantly higher in low vitamin D state compared with high vitamin D state(P<0.05);the correlation between hypovitaminosis D status and renal Ki-67 was found to be positive.Conclusion:The results showed that serum IL-6 levels were elevated in the cancer group and circulating serum 25(OH)D levels were negatively correlated with IL-6 levels.In addition,signal transducer and activator of transcription 3(STAT3)signaling in RCC tissues was activated in ccRCC patients and in those with low vitamin D status among the cancer group and was higher than that in those with high vitamin D status.These results suggest that hypovitaminosis D status in ccRCC patients is associated with activated IL-6/STAT3 signaling and the activation of tumor proliferation markers proliferating cell nuclear antigen(PCNA),cyclin D1,and Ki-67.

Metastatic clear cell renal cell carcinoma in isolated retroperitoneal lymph node without evidence of primary tumor in kidneys: A case report

BACKGROUND Retroperitoneal lymph node dissection(RPLND)plays a diagnostic,therapeutic,and prognostic role in myriad urologic malignancies,including testicular carcinoma,renal cell carcinoma(RCC),and upper urinary tract urothelial carcinoma.RCC represents 2%of all cancers with approximately 25%of patients presenting with advanced disease.Clear cell RCC(CCRCC)is the most common RCC,accounting for 75%-80%of all RCC.CASE SUMMARY A 71-year-old man presented with a history of benign prostatic hypertrophy.He was asymptomatic without any hematuria,pain,or other urinary symptoms.A computed tomography(CT)scan of the abdomen and pelvis showed a 1.8 cm left retroperitoneal lymph node.There was no evidence of renal pathology.A core biopsy was performed of the left para-aortic lymph node.Although the primary tumor site was unknown,the morphological and immunohistochemical features were most consistent with CCRCC.A RPLND was performed which revealed a single mass 5.5 cm in greatest dimension with extensive necrosis.The retroperitoneal lymph node was most compatible with CCRCC.A nephrectomy was not conducted as a renal mass had not been detected on any prior imaging studies.The patient did not receive any type of adjuvant therapy.The patient underwent surveillance with serial CT scans with contrast of the chest,abdomen,and pelvis for the next 5 years,all of which demonstrated no recurrent or metastatic disease and no evidence of retroperitoneal adenopathy.CONCLUSION Our unique case emphasizes the therapeutic role of metastasectomy in metastatic CCRCC even in the absence of primary tumor in the kidneys.

Memory stem T cells generated by Wnt signaling from blood of human renal clear cell carcinoma patients

Objective: Memory stem T cells(Tscm) have attracted attention because of their enhanced self-renewal, multipotent capacity, and anti-tumor capacities. However, little is known about Tscm in patients with renal clear cell carcinoma(RCC) and the role of Wnt signaling in these cells. We evaluated Tscm from RCC patients concerning their activation of Wnt signaling in vitro and explored the mechanism of preferential survival.Methods: Flow cytometry identified surface markers and cytokines produced from accumulated Tscm in the presence of the glycogen synthase kinase beta inhibitor TWS119. Apoptosis was evaluated after induction using tumor necrosis factor-alpha.Immunofluorescence and Western blot analyses were used to investigate the activation of the nuclear factor-kappa B(NF-КB)pathway.Results: RCC patients had a similar percentage of CD4^+ and CD8^+ Tscm as healthy donors. Activation of Wnt signaling by TWS119 resulted in the accumulation of Tscm in activated T cells, but reversal of differentiated T cells to Tscm was not achieved.Preferential survival of Tscm was associated with increased anti-apoptotic ability mediated downstream of the NF-КB activation pathway.Conclusions: The finding that Tscm can accumulate by Wnt signaling in vitro in blood from RCC patients will help in devising new cancer therapy strategies of Tscm-based adoptive immunotherapy, such as dendritic cell-stimulated Tscm, and T cell receptor or chimeric antigen receptor-engineered Tscm.

Epigenomics of clear cell renal cell carcinoma： mechanisms and potential use in molecular pathology

Clear cell renal cell carcinoma （ccRCC） is one frequent form of urologic malignancy with numerous genetic and epigenetic alterations. This review summarizes the recent major findings of epigenetic alterations including DNA methylation, histone modifications, microRNAs and recently identified long noncoding RNAs in the development and progression of ccRCC. These epigenetic profilings can provide a promising means of prognostication and early diagnosis for patients with ccRCCs. With the developed high- throughput technologies nowadays, the epigenetic analyses will have possible clinical applications in the molecular pathology of ccRCC.

Aberrant DNA methyltransferase 1 expression in clear cell renal cell carcinoma development and progression

Objective： To better understand the contribution of dysregulated DNA methyltransferase 1 （DNMT1） expression to the progression and biology of clear cell renal cell carcinoma （ccRCC）. Methods： We examined the differences in the expression of DNMT1 in 89 ecRCC and 22 normal tissue samples by immunohistochemistry. In addition, changes in cell viability, apoptosis, colony formation and invading ability of ccRCC cell lines （786-0 and Caki-1） were assessed after transfection with DNMT1 siRNA. Results： We found DNMT1 protein was significantly higher expressed in ccRCC than that of in no-tumor tissues （56.2% and 27.3%, respectively, P=0.018）. The expression of DNMT1 was strongly associated with ccRCC tumor size, tumor pathology stage, histological grading, lymph node metastasis, vascular invasion, recurrence and prognosis. Moreover, knockdown of DNMT1 expression significantly inhibited ccRCC cell viability, induced apoptosis, decreased colony formation and invading ability. Conclusions： Expression of DNMTI protein is increased in ccRCC tissues, and DNMT1 expression is associated with poor prognosis of patients. Experiments in vitro further showed DNMT1 played an essential role in proliferation and invasion of renal cancer cells. Moreover, targeting this enzyme could be a promising strategy for treating ccRCC, as evidenced by inhibited cell viability, increased apoptosis, decreased colony formation and invading ability.

Primary small cell carcinoma of kidney after renal transplantation:a case report and literature review

Extrapulmonary small cell carcinoma （EPSCC） is a rare neoplasm comprising 2.5％ to 5％ of small cell carcinomas （SCCs）.Bladder SCC is the most common site of genitourinary tract.Primary renal SCC is extremely rare.We report a case of primary SCC of the kidney which is rarely reported in the urinary tract and presents an aggressive clinical picture.A 59-year-old female visited a urologic clinic with complaint of persistent left flank soreness 10 years after undergoing renal transplantation.Abdominal computed tomography showed a left renal pelvis tumor.After the patient received left nephroureterectomy with bladder cuff resection,her pathology results showed SCC.After surgery,she received adjuvant systemic chemotherapy,and her recovery has been uneventful as of 8 months.Primary renal SCC presents with an advanced tumor stage and a short median survival period,therefore early intervention and close follow-up are recommended.

Clival metastasis of renal clear cell carcinoma: Case report and literature review

The clivus is an atypical metastatic site for renal clear cell carcinoma(RCCC). Here we report a 54 year old man with acute cavernous sinus syndrome. Brain magnetic resonance imaging identified a clival-based lesion with associated bony erosion. The patient underwent endoscopic endonasal biopsy and partial resection of the clival mass. Because histologic examination of the resected specimen resulted in a diagnosis of RCCC, contrast-enhanced computed tomography scan of the abdomen was performed and showed an enhanced left renal mass. The patient subsequently underwent laparoscopic left radical nephrectomy and gamma knife was planned for the residual clival lesion. We also retrospectively reviewed available published reports on clival metastases, specifically those from RCCC, since 1990.

Netrin-1:the new tumor markers in renal clear cell carcinoma

Objective:To explore the expression of Netrin-1 protein in human renal clear cell carcinoma(RCCC) and the relationships between Netrin-1.pathology and prognosis.Methods:72 cases of RCCC admitted in our hospital from 2008 June to 2009 June and their adjacent tissues were selected for study.They included 30 cases in stage Ⅰ-Ⅱ.42 cases in stage Ⅲ-Ⅳ;9 cases in grade Ⅰ.9 cases in grade Ⅱ.40 cases in grade Ⅲ and 14 cases in grade Ⅳ.All cases were followed up for more than 5 years.Survival analysis lines were made by Kaplan—Meier method and the difference between groups was tested by the Log-rank test.The expression of Netrin-1 protein was detected by immunohistochemistry staining and its clinical significance was analyzed.Results:Renal clear cell carcinoma:51 cases in high expression of Netrin-1and 21 cases in low expression,normal tissues:12 cases in high expression of Netrin-1and 60 cases in low expression,the difference between the two groups is significant(x^2=42.921,P<0.01).The difference of the expression of Netrin-lin Fuhrman grade and AJCC clinical stage is significant(x^2=8.000.x^2=6.203:P<0.05).The 5-year survival rate in low protein expression group and in high protein expression group was 79% (17/21) and 62% (32/51).The survival curve had different trend,with no significant difference between groups(x^2=1.360.P=0.245).Conclusions:Netrin-1 protein plays an important role in the development of RCCC.It might be a new specific tumor marker of RCCC.and might become a new target in treatment of RCCC.

Application of the revised Tumour Node Metastasis （TNM） staging system of clear cell renal cell carcinoma in eastern China： advantages and limitations

This study was designed to evaluate whether the revised 2010 Tumour Node Metastasis （TNM） staging system could lead to a more accurate prediction of the prognosis of renal cell carcinoma （RCC） patients. A total of 1216 patients who had undergone radical nephrectomy or partial nephrectomy for RCC from 2003 to 2011 were enrolled. All of the patients had pathologically confirmed clear cell RCC （ccRCC）. All cases were staged by both the 2002 and 2010 TNM staging systems after pathological review, and survival data were collected. Univariate and multivariate Cox regression models were used to evaluate cancer-specific survival （CSS） and progression-free survival （PFS） after surgery. Continuous variables, such as age and tumour diameter, were calculated as mean values and standard deviations （s.d.） or as median values. Survival was calculated by the Kaplan-Meier method, and the log-rank test assessed differences between groups. Statistically significant differences in CSS and PFS were noted among patients in T3 subgroups using the new 2010 staging system. Therefore, the revised 2010 TNM staging system can lead to a more accurate prediction of the prognosis of ccRCC patients. However, when using the revised 2010 staging system, we found that more than 92% of patients （288/313） with T3 tumours were staged in the T3a subgroup, and their survival data were not significantly different from those of patients with T2b tumours. In addition, T2 subclassification failed to independently predict survival in RCC patients.

Correlation Between Hyaluronic Acid,Hyaluronic Acid Synthase And Human Renal Clear Cell Carcinoma

Objective：To study the correlation between hyaluronic acid（HA）,hyaluronic acid synthase（HAS） and human renal clear cell carcinoma（RCCC）.Methods：The expression of three HAS isoforms＇ gene and HA in 93 RCCC tissues,27 nephridial tissues by the side of RCCC from two hospitals were measured with Real-Time RT-PCR、Western Blot and immunohistochemical methods and analyzed.Results：All RCCC and adjacent normal tissues expressed three HASs＇ mRNA protein;at the mRNA level,both RCCC and adjacent normal tissues,expressed more HAS3 than HAS1 or HAS2,their differences were statistically significant（all P values 0.05）;but,at the protein level,all HAS isoforms presented the equivalent expression.Compared with the adjacent non-neoplastic kidney tissues,the expression of all HAS isoforms＇ mRNA in RCCC tissues were increased evidently and their differences were significant（all P values 0.0001）;but at the protein level,only the expression of HAS3 increased evidently（P=0.022）.In all adjacent normal tissues,more than 80% renal tubular cells strongly expressed HA,however,only the minority RCCC cases（16/93） presented weakly positive HA staining in few cancer nests（5%-30%）,the difference were significant（P0.0001）.In RCCC tissues subgrouped according to clinical stage,pathological grade,lymphatic metastasis or not and distant metastasis or not,the HASs＇ mRNA protein differential expression all had no statistical significance（all P values 0.05）.Conclusion：Different from other malignancy,HA and HASs（except for HAS3） may not play important roles in the biological progress of human RCCC.

Clear cell papillary renal cell carcinoma: A case report and review of the literature

Clear cell papillary renal cell carcinoma(ccpRCC) was recently established as a distinct type of epithelial neoplasm by the International Society of Urological Pathology Vancouver Classification of Renal Neoplasia. Here,we report a case of partial nephrectomy for a ccpRCC detected during the routine follow-up of a previously treated liposarcoma in a 70-year-old male patient. The patient was referred to the urology department for a right-sided renal mass(size: 2 cm)detected during routine annual imaging follow-up for a malignant right inguinal fibrous histocytoma and liposarcoma that had been diagnosed 6 and 4 years earlier,respectively,and treated with surgery and adjuvant radiation therapy.Following partial nephrectomy,the renal mass was pathologically diagnosed as ccpRCC,and immunohistochemistry revealed carbonic anhydrase 9(CA9)expression. No recurrences or metastases were detected on follow-up imaging for6 months. This is the first report of partial nephrectomy for incidentally discovered CA9-positive ccpRCC.

RNF43 is a novel tumor-suppressor and prognostic indicator in clear cell renal cell carcinoma

Identifying prognostic indicators of clear cell renal cell carcinoma(ccRCC)and elucidating the mechanisms underlying ccRCC progression are crucial for improving ccRCC patient prognosis.This study investigated the clinical significance and biological role of Ring finger protein 43(RNF43)in ccRCC.Two independent cohorts of patients with ccRCC were employed to determine the prognostic significance of RNF43 by immunohistochemistry and statistical analyses.In vitro and in vivo experiments,RNA-seq,and other techniques were used to determine the biological role of RNF43 in ccRCC and related molecular mechanisms.RNF43 expression was commonly decreased in ccRCC specimens,and low expression of RNF43 indicated a higher TNM stage,SSIGN score,and WHO/ISUP grade and short survival in patients with ccRCC.Additionally,RNF43 overexpression suppressed the proliferation,migration,and targeted drug resistance of ccRCC cells,while the knockdown of RNF43 enhanced these characteristics of ccRCC.RNF43 knockdown activated YAP signaling by decreasing YAP phosphorylation by p-LATS1/2 and increasing the transcription and nuclear distribution of YAP.By contrast,RNF43 overexpression showed the opposite effects.Decreasing YAP abolished the effect of RNF43 knockdown in promoting the malignant features of ccRCC.Additionally,restoring RNF43 expression suppressed the resistance of the targeted drug pazopanib in in vivo orthotopic ccRCC.Furthermore,combining the expression of RNF43 and YAP with TNM stage or the SSIGN score exhibited greater accuracy than any of these indicators alone in assessing the postoperative prognosis of ccRCC patients.In summary,our study identified a novel tumor suppressor,RNF43,which is also a prognostic indicator and potential target for ccRCC.