Ipsilateral retroperitoneal papillary renal cell carcinoma 27 years after simple nephrectomy for a renal abscess:A case report

BACKGROUND Cases of severe inflammatory renal disease and renal cell carcinoma(RCC)that occur simultaneously in the same kidney have been occasionally reported.However,extrarenal RCC that does not originate from the native kidney has rarely been reported.To our knowledge,this is the first reported case of RCC developing in the ipsilateral retroperitoneal space after a simple nephrectomy(SN)for inflammatory renal disease.CASE SUMMARY A 63-year-old woman was referred to our hospital following the incidental discovery of a left retroperitoneal mass without specific symptoms.Her medical history revealed a left SN 27 years ago due to a renal abscess.Magnetic resonance imaging of the abdomen revealed three oval masses in the left retroperitoneum.The masses were successfully excised,and subsequent pathology confirmed papillary RCC.After surgery,the patient remained disease-free for 11 years without adjuvant therapy.CONCLUSION Clinicians should be vigilant of RCC in patients with retroperitoneal masses,especially after SN for inflammatory renal disease.

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.

Optimal sequential therapy using tyrosine kinase inhibitors as the first-line treatment in patients with metastatic renal cell carcinoma: A nationwide multicenter study

Objective:The purpose of the study was to identify the best sequence of therapy beginning with a tyrosine kinase inhibitor(TKI)as the first-line therapy for patients with metastatic renal cell carcinoma(mRCC)in terms of overall survival(OS),progression-free survival(PFS),and rates of discontinuation and adverse effects during the treatment period.Methods:This is a retrospective,nationwide multicenter study of patients with mRCC after diagnosis at 10 different tertiary medical centers in Korea from January 1992 to December 2017.We focused on patients at either“favorable”or“intermediate”risk according to the International mRCC Database Consortium criteria,and they were followed up(median 335 days).Finally,a total of 1409 patients were selected as the study population.We generated a Cox proportional hazard model adjusted for covariates,and the different therapy schemes were statistically tested in terms of OS as well as PFS.In addition,frequencies of discontinuation and adverse events were compared among the therapy schemes.Results:Of the primary patterns of treatment sequences(24 sequences),“sunitinib epazopanib”and“sunitinibeeverolimuseimmunotherapy”showed the most beneficial results in both OS and PFS with significantly lower hazards than“sunitinib”,which is the most commonly treated agent in Korea.Considering that the“TKIeTKI”structure showed relatively higher discontinuation rates with higher adverse effects,the overall beneficial sequence would be“sunitinibeeverolimuseimmunotherapy”.Conclusion:Among several sequential therapy starting with TKIs,“sunitinibeeverolimuse immunotherapy”was found to be the best scheme for mRCC patients with“favorable”or“intermediate”risks.

Toripalimab in combination with chemotherapy effectively suppresses local recurrence and metastatic sarcomatoid renal cell carcinoma:A case report

BACKGROUND Sarcomatoid renal cell carcinoma(SRCC)is a rare variant of renal cell carcinoma associated with an unfavorable prognosis.The efficacy of conventional chemo-therapy and targeted therapies are limited,whereas the emergence of immune checkpoint inhibitor has introduced new avenues for managing advanced SRCC.CASE SUMMARY A 77-year-old female patient was referred to our hospital following the incidental detection of a right kidney tumor without specific symptoms.The tumor was successfully resected,and subsequent pathological examination confirmed SRCC.She experienced both local recurrence and distant metastasis eight months after the initial laparoscopic resection.Following six cycles of toripalimab combined with pirarubicin chemotherapy,the patient achieved a partial response.Subse-quently,the patient attained an almost-complete continuous response to toripa-limab monotherapy maintenance for an additional six cycles.She has not experienced disease progression for 15 months,and her overall survival has reached 24 months thus far.CONCLUSION Combination therapy with programmed death 1 antibodies and cytotoxic agents may be a recommended first-line treatment approach for SRCC.

Comprehensive assessment of the association between tumorinfiltrating immune cells and the prognosis of renal cell carcinoma

BACKGROUND According to current statistics,renal cancer accounts for 3%of all cancers world-wide.Renal cell carcinoma(RCC)is the most common solid lesion in the kidney and accounts for approximately 90%of all renal malignancies.Increasing evi-dence has shown an association between immune infiltration in RCC and clinical outcomes.To discover possible targets for the immune system,we investigated the link between tumor-infiltrating immune cells(TIICs)and the prognosis of RCC.AIM To investigate the effects of 22 TIICs on the prognosis of RCC patients and iden-tify potential therapeutic targets for RCC immunotherapy.METHODS The CIBERSORT algorithm partitioned the 22 TIICs from the Cancer Genome Atlas cohort into proportions.Cox regression analysis was employed to evaluate the impact of 22 TIICs on the probability of developing RCC.A predictive model for immunological risk was developed by analyzing the statistical relationship between the subpopulations of TIICs and survival outcomes.Furthermore,multi-variate Cox regression analysis was used to investigate independent factors for the prognostic prediction of RCC.A value of P<0.05 was regarded as statistically significant.RESULTS Compared to normal tissues,RCC tissues exhibited a distinct infiltration of im-mune cells.An immune risk score model was established and univariate Cox regression analysis revealed a significant association between four immune cell types and the survival risk connected to RCC.High-risk individuals were correlated to poorer outcomes according to the Kaplan-Meier survival curve(P=1E-05).The immunological risk score model was demonstrated to be a dependable predictor of survival risk(area under the curve=0.747)via the receiver operating characteristic curve.According to multivariate Cox regression analysis,the immune risk score model independently predicted RCC patients'prognosis(hazard ratio=1.550,95%CI:1.342–1.791;P<0.001).Finally,we established a nomogram that accurately and comprehensively forecast the survival of patients with RCC.CONCLUSION TIICs play various roles in RCC prognosis.The immunological risk score is an independent predictor of poor survival in kidney cancer cases.

Advances in treatment strategies for non–clear cell renal cell carcinoma

Renal cell carcinoma is the sixth most commonly diagnosed cancer in men and the tenth in women,with clear cell renal cell carcinoma accounting for nearly 75%of cases.The remaining 25%consists of non–clear cell renal cell carcinoma,a diverse and less prevalent group.Although current treatments for clear cell types are well-defined,progress in treating non–clear cell renal cell carcinoma has been limited owing to its heterogeneity and rarity,relying primarily on findings from small-scale phase Ⅱ clinical trials.This review examined recent advancements in the treatment of non–clear cell renal cell carcinoma,particularly in the areas of immunotherapy and targeted therapy.

Eosinophilic solid and cystic renal cell carcinoma with aggressive behavior:Two case reports

BACKGROUND Eosinophilic solid and cystic(ESC)renal cell carcinoma(RCC),a unique and emerging subtype of RCC,has an indolent nature;in some rare instances,it may exhibit metastatic potential.Current cases are inadequate to precisely predict the clinical outcome of ESC RCC and determine treatment choices.CASE SUMMARY Herein,we report two patients with ESC RCC.Patient 1 was a young woman with classical pathological characteristics.Patient 2 was a 52-year-old man with multifocal metastases,involving the pulmonary hilar and mediastinal lymph nodes,liver,brain,mesosternum,vertebra,rib,femur,and symphysis pubis.Awareness of ESC RCC,along with its characteristic architecture and immunophenotype,would contribute to making a definitive diagnosis,even on core biopsy samples.CONCLUSION The discovery of ESC RCC molecular signatures may provide new therapeutic strategies in the future.

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.

TDERS,an exosome RNA-derived signature predicts prognosis and immunotherapeutic response in clear cell renal cell cancer:a multicohort study

Background:Tumor-derived exosomes are involved in tumor progression and immune invasion and might func-tion as promising noninvasive approaches for clinical management.However,there are few reports on exosom-based markers for predicting the progression and adjuvant therapy response rate among patients with clear cell renal cell carcinoma(ccRCC).Methods:The signatures differentially expressed in exosomes from tumor and normal tissues from ccRCC pa-tients were correspondingly deregulated in ccRCC tissues.We adopted a two-step strategy,including Lasso and bootstrapping,to construct a novel risk stratification system termed the TDERS(Tumor-Derived Exosome-Related Risk Score).During the testing and validation phases,we leveraged multiple external datasets containing over 2000 RCC cases from eight cohorts and one inhouse cohort to evaluate the accuracy of the TDERS.In addition,enrichment analysis,immune infiltration signatures,mutation landscape and therapy sensitivity between the high and low TDERS groups were compared.Finally,the impact of TDERS on the tumor microenvironment(TME)was also analysed in our single-cell datasets.Results:TDERS consisted of 12 mRNAs deregulated in both exosomes and tissues from patients with ccRCC.TDERS achieved satisfactory performance in both prognosis and immune checkpoint inhibitor(ICI)response across all ccRCC cohorts and other pathological types,since the average area under the curve(AUC)to predict 5-year overall survival(OS)was larger than 0.8 across the four cohorts.Patients in the TDERS high group were resistant to ICIs,while mercaptopurine might function as a promising agent for those patients.Patients with a high TDERS were characterized by coagulation and hypoxia,which induced hampered tumor antigen presentation and relative resistance to ICIs.In addition,single cells from 12 advanced samples validated this phenomenon since the interaction between dendritic cells and macrophages was limited.Finally,PLOD2,which is highly expressed in fibro-and epi-tissue,could be a potential therapeutic target for ccRCC patients since inhibiting PLOD2 altered the malignant phenotype of ccRCC in vitro.Conclusion:As a novel,non-invasive,and repeatable monitoring tool,the TDERS could work as a robust risk stratification system for patients with ccRCC and precisely inform treatment decisions about ICI therapy.

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.

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.

Differentiate Xp11.2 Translocation Renal Cell Carcinoma from Computed Tomography Images and Clinical Data with ResNet-18 CNN and XGBoost

This study aims to apply ResNet-18 convolutional neural network(CNN)and XGBoost to preoperative computed tomography(CT)images and clinical data for distinguishing Xp11.2 translocation renal cell carcinoma(Xp11.2 tRCC)from common subtypes of renal cell carcinoma(RCC)in order to provide patients with individualized treatment plans.Data from45 patients with Xp11.2 tRCC fromJanuary 2007 to December 2021 are collected.Clear cell RCC(ccRCC),papillary RCC(pRCC),or chromophobe RCC(chRCC)can be detected from each patient.CT images are acquired in the following three phases:unenhanced,corticomedullary,and nephrographic.A unified framework is proposed for the classification of renal masses.In this framework,ResNet-18 CNN is employed to classify renal cancers with CT images,while XGBoost is adopted with clinical data.Experiments demonstrate that,if applying ResNet-18 CNN or XGBoost singly,the latter outperforms the former,while the framework integrating both technologies performs similarly or better than urologists.Especially,the possibility of misclassifying Xp11.2 tRCC,pRCC,and chRCC as ccRCC by the proposed framework is much lower than urologists.

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.

A developed ant colony algorithm for cancer molecular subtype classification to reveal the predictive biomarker in the renal cell carcinoma

Background:Recently,researchers have been attracted in identifying the crucial genes related to cancer,which plays important role in cancer diagnosis and treatment.However,in performing the cancer molecular subtype classification task from cancer gene expression data,it is challenging to obtain those significant genes due to the high dimensionality and high noise of data.Moreover,the existing methods always suffer from some issues such as premature convergence.Methods:To address those problems,we propose a new ant colony optimization(ACO)algorithm called DACO to classify the cancer gene expression datasets,identifying the essential genes of different diseases.In DACO,first,we propose the initial pheromone concentration based on the weight ranking vector to accelerate the convergence speed;then,a dynamic pheromone volatility factor is designed to prevent the algorithm from getting stuck in the local optimal solution;finally,the pheromone update rule in the Ant Colony System is employed to update the pheromone globally and locally.To demonstrate the performance of the proposed algorithm in classification,different existing approaches are compared with the proposed algorithm on eight high-dimensional cancer gene expression datasets.Results:The experiment results show that the proposed algorithm performs better than other effective methods in terms of classification accuracy and the number of feature sets.It can be used to address the classification problem effectively.Moreover,a renal cell carcinoma dataset is employed to reveal the biological significance of the proposed algorithm from a number of biological analyses.Conclusion:The results demonstrate that CAPS may play a crucial role in the occurrence and development of renal clear cell carcinoma.

Single omental metastasis of renal cell carcinoma after radical nephrectomy:A case report

BACKGROUND Renal cell carcinoma(RCC)is the third most common malignancy in the genitourinary tract.The lungs,bone,lymph nodes,liver,and brain are common metastatic sites of RCC.However,there is limited literature on single omental metastasis of RCC.CASE SUMMARY We present the case of a 44-year-old man with single omental metastasis of RCC after laparoscopic radical nephrectomy.Pathological diagnosis of the resected left kidney revealed pT3a clear cell RCC(Fuhrman grade III).At 6 mo postoperatively,abdominal computed tomography revealed a 12-mm enhancing nodule in the left lower peritoneum.At 7 mo after initial operation,laparoscopic removal of the left omental nodule was performed.The pathological results indicated metastatic clear cell RCC.Currently,the patient is being treated with adjuvant pembrolizumab.CONCLUSION Omental metastasis of RCC owing to laparoscopic radical nephrectomy is rare.Urologists should be aware of the diverse nature of RCC.

Warthin-like papillary renal cell carcinoma: A case report

BACKGROUND Warthin-like papillary renal cell carcinoma(WPRCC)has been described as a rare pathological subtype of papillary renal cell carcinoma in the 2022 World Health Organization Classification of the Urinary and Male Reproductive System.Herein we report a case of WPRCC in the left kidney.CASE SUMMARY Physical examination of a previously healthy 47-year-old woman revealed a lump in her left kidney,4.5 cm×3.5 cm×3.5 cm in size.Based on the clinical information,imaging data,histmorphological features,and immunohistochemistry results,the pathological diagnosis was WPRCC in left kidney.CONCLUSION Resection of the mass in the left kidney was performed and her postoperative course was uneventful.

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.

Tumor microenvironment-based signatures distinguish intratumoral heterogeneity, prognosis, and immunogenomic features of clear cell renal cell carcinoma

Background:The tumor microenvironment(TME)performs a crucial function in the tumorigenesis and response to immunotherapies of clear cell renal cell carcinoma(ccRCC).However,a lack of recognized pre-clinical TME-based risk models poses a great challenge to investigating the risk factors correlated with prognosis and treatment responses for patients with ccRCC.Methods:Stromal and immune contexture were assessed to calculate the TMErisk score of a large sample of patients with ccRCC from public and real-world cohorts using machine-learning algorithms.Next,analyses for prognostic efficacy,correlations with clinicopathological features,functional enrichment,immune cell distribu-tions,DNA variations,immune response,and heterogeneity were performed and validated.Results:Clinical hub genes,including INAFM2,SRPX,DPYSL3,VSIG4,APLNR,FHL5,A2M,SLFN11,ADAMTS4,IFITM1,NOD2,CCR4,HLA-DQB2,and PLAUR,were identified and incorporated to develop the TMErisk signature.Patients in the TME high risk group(category)exhibited a considerably grim prognosis,and the TMErisk model was shown to independently function as a risk indicator for the overall survival(OS)of ccRCC patients.Expression levels of immune checkpoint genes were substantially increased in TME high risk group,while those of the human leukocyte antigen(HLA)family genes were prominently decreased.In addition,tumors in the TME high group showed significantly high infiltration levels of tumor-infiltrated lymphocytes,including M2 macrophages,CD8+T cells,B cells,and CD4+T cells.In heterogeneity analysis,more frequent somatic mutations,including pro-tumorigenic BAP1 and PBRM1,were observed in the TME high group.Importantly,19.3%of patients receiving immunotherapies in the TME high group achieved complete or partial response compared with those with immune tolerance in the TME low group,suggesting that TMErisk prominently differentiates prognosis and responses to immunotherapy for patients with ccRCC.Conclusions:We first established the TMErisk score of ccRCC using machine-learning algorithms based on a large-scale population.The TMErisk score can be utilized as an innovative independent prognosis predictive marker with high sensitivity and accuracy.Our discovery also predicted the efficacy of immunotherapy in ccRCC patients,indicating the intimate link between tumor immune microenvironment and intratumoral heterogeneity.

Heterogeneity and function of cancer-associated fibroblasts in renal cell carcinoma

With the advancement of anticancer therapy,there is increasing interest in understanding the tumor microenvi-ronment(TME).Cancer-associated fibroblasts(CAFs)play a pivotal role in the TME and have been the focus of much research in recent years.CAFs play an active role in cancer progression through complex interactions with other cells in the TME,releasing regulatory factors,synthesizing and remodeling the extracellular matrix.How-ever,research on the role of CAFs in renal cell carcinoma(RCC)is still in its nascent stages.Here,we describe the origins and subgroups of CAFs,the roles of CAFs in the development and progression of RCC,the impact of CAFs on RCC prognosis,and the potential of CAFs as treatment targets in RCC.By analyzing CAF subsets,biomarkers,and targeted therapies,we present the significance and contribution of CAFs in RCC research.Furthermore,we highlight the distinct contribution of CAFs in advanced RCC through horizontal comparison with other cancers.This paper provides a comprehensive perspective of recent and foundational studies on the role of CAFs in RCC and other types of cancers and new insights for further study of CAFs in RCC.

Multilocular Cystic Renal Cell Carcinoma:A Series of 8 Cases and Review of the Literature

OBJECTIVE To study the clinical, pathologic and imaging features of multilocular cystic renal cell carcinoma （MCRCC） and to review the diagnosis and treatment of this subtype of renal cell carcinoma （RCC）. METHODS The data from 8 cases （mean age, 49.4; 5 men and 3 women） who had been treated from 2004 to 2006, were reviewed retrospectively. Radiologic and pathologic documents were evaluated. For treatments, radical nephrectomy was conducted in 4 patients, partial nephrectomy in 2 and laparoscopic nephrectomy in 2. RESULTS Postoperative pathological findings confirmed the diagnosis of MCRCC. The stage of all 8 cases was pT1. For pathologic grade, 7 cases were G1 and 1 case was G2. Seven patients available for follow-up had survived tumor-free during the mean time of 8 months. CONCLUSION MCRCC is an uncommon subtype of RCC, it has a lower malignant potential and a better prognosis compared with other types of RCC. Nephron-sparing surgery may be an appropriate treatment options for MCRCC.