Factor In Renal Cell Carcinoma Research Articles

Renal Cell Carcinoma in End-Stage Renal Disease: A Retrospective Study in Patients from Hungary

Introduction: End-stage renal disease (ESRD) and acquired cystic kidney disease (ACKD) are known risk factors for renal cell carcinoma (RCC). Hereby, the clinicopathological features of RCCs developed in ESRD were investigated. Methods: A database consisting of 34 tumors from 31 patients with ESRD among 2,566 nephrectomy samples of RCC was built. The demographic, clinical, and follow-up data along with pathological parameters were analyzed. The RCCs were diagnosed according to the current WHO Classification of Urinary and Male Genital Tumors. Results: Twenty-two tumors developed in men and 12 in women, with a median age of 56 years (range: 27–75 years). The causes of ESRD were glomerulonephritis (n = 7), hypertensive kidney disease (n = 6), autosomal dominant polycystic kidney disease (n = 6), chronic pyelonephritis (n = 4), diabetic nephropathy (n = 3), chemotherapy-induced nephropathy (n = 1), and undetermined (n = 4). ACKD complicated ESRD in 12 patients. The following histological subtypes were identified: clear cell RCC (n = 19), papillary RCC (n = 5), clear cell papillary tumor (n = 5), ACKD RCC (n = 3), and eosinophilic solid and cystic RCC (n = 2). The median tumor size was 31 mm (range: 10–80 mm), and 32 tumors were confined to the kidney (pT1-pT2). There was no tumor-specific death during the period of this study. Progression was registered in 1 patient. Conclusion: In our cohort, the most common RCC subtype was clear cell RCC (55%), with a frequency that exceeded international data appreciably (14–25%). The incidence of clear cell papillary tumor and ACKD RCC (14.7% and 8.5%) was lower than data reported in the literature (30% and 40%). Our results indicate a favorable prognosis of RCC in ESRD.

MiT/TFE Family Renal Cell Carcinoma.

The microphthalmia-associated transcription factor/transcription factor E (MiT/TFE) family of transcription factors are evolutionarily conserved, basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factors, consisting of MITF, TFEB, TFE3, and TFEC. MiT/TFE proteins, with the exception of TFEC, are involved in the development of renal cell carcinoma (RCC). Most of the MiT/TFE transcription factor alterations seen in sporadic RCC cases of MiT family translocation renal cell carcinoma (tRCC) are chimeric proteins generated by chromosomal rearrangements. These chimeric MiT/TFE proteins retain the bHLH-Zip structures and act as oncogenic transcription factors. The germline variant of MITF p.E318K has been reported as a risk factor for RCC. E 318 is present at the SUMOylation consensus site of MITF. The p.E318K variant abrogates SUMOylation on K 316, which results in alteration of MITF transcriptional activity. Only a few cases of MITF p.E318K RCC have been reported, and their clinical features have not yet been fully described. It would be important for clinicians to recognize MITF p.E318K RCC and consider MITF germline testing for undiagnosed familial RCC cases. This review outlines the involvement of the MiT/TFE transcription factors in RCC, both in sporadic and hereditary cases. Further elucidation of the molecular function of the MiT/TFE family is necessary for better diagnosis and treatment of these rare diseases.

肾细胞癌的高危因素

肾细胞癌的高危因素

Clinicopathologic factors linked to oncologic outcomes for renal cell carcinoma with sarcomatoid dedifferentiation: A PRISMA-compliant systematic review and meta-analysis.

There are still differences in the prognostic factors of renal cell carcinoma with sarcomatoid dedifferentiation (sRCC). The aim of this study was to evaluate important predictors of survival in patients with sRCC. A comprehensive search of PubMed, Embase, and Cochrane Library was conducted to identify eligible studies. The endpoints embraced overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). Hazard ratios (HRs) and related 95% confidence intervals (CIs) were extracted. A total of 13 studies were included for analyses. The pooled results showed that high European Cooperative Oncology Group performance score (HR 2.39, 95% CI 1.32-4.30; P = 0.004), high T stage (HR 2.18, 95% CI 1.66-2.86; P < 0.001), positive lymph node (HR 1.54, 95% CI 1.40-1.69; P < 0.001), distant metastasis (HR 2.52, 95% CI 1.99-3.21; P < 0.001), lung metastases (HR 1.45, 95% CI 1.16-1.80; P < 0.001), liver metastases (HR 1.71, 95% CI 1.30-2.25; P < 0.001), tumor necrosis (HR 1.78, 95% CI 1.14-2.80; P = 0.010), and percentage sarcomatoid ≥50% (HR 2.35, 95% CI 1.57-3.52; P < 0.001) were associated with unfavorable OS. Positive lymph node (HR 1.57, 95% CI 1.33-1.85; P < 0.001) and high neutrophil to lymphocyte ratio (HR 1.16, 95% CI 1.04-1.29; P = 0.008) were associated with unfavorable CSS. High T stage (HR 1.93 95% CI 1.44-2.58; P < 0.001) was associated with unfavorable progression-free survival. A meta-analysis of available data identified important prognostic factors for CSS, OS, and PFS of sRCC, which should be systematically evaluated for patient counseling, risk stratification, and treatment selection. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=249449.

Prognostic factors of renal cell carcinoma.

Renal cell carcinoma represents 23% of all adult malignancies and its incidence in the Czech Republic is one of the highest worldwide. Until late stages this disease often remains asymptomatic, which makes its diagnosis difficult. Despite an increasing proportion of small, incidentally detected tumours on imaging, approximately one third of patients are still diagnosed with advanced disease. Moreover, a relapse occurs in up to 40% of patients after surgery for localized tumour. Increased availability of imaging investigations allowing an early detection of kidney carcinoma and advances in systemic treatment have favourably affected the outcome of patients with this type of tumour. Nevertheless, mortality of renal cell carcinoma remains the highest among urological malignancies. The individual course of the disease and its response to systemic treatment are difficult to predict. A number of prognostic factors of renal cell carcinoma have been identified, of which TNM classification and tumour grade remain the most important. Recently, several multivariate prognostic models have become available, allowing a more accurate prediction of the disease course. In localized disease, they are useful in identifying patients at higher risk of recurrence and allow optimization of follow-up after surgery. In metastatic disease, they are routinely used to stratify patients into risk groups for targeted treatment. There has been a long-term effort to identify a suitable biomarker useful for an early detection and assessment of the prognosis of renal cell carcinoma. At the same time, such a biomarker could improve the accuracy of established prognostic systems. This text presents an overview of prognostic factors of renal cell carcinoma, including a summary of potential biomarkers.

Preoperative neutrophil-lymphocyte ratio/platelet-lymphocyte ratio: A potential and economical marker for renal cell carcinoma.

Emerging evidences have elucidated the crucial role of inflammation in carcinogenesis and tumor progression. In the recent years, many inflammatory biomarkers showed promising prognostic factors in renal cell carcinoma (RCC). We intended to evaluate the significance of one such inflammatory factor which is potential, noninvasive, simple, as well as economical. The preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in RCC patients have shown favorable results. The objective was to assess the prognostic role of NLR/PLR in the advanced stage and high-grade RCC. This is a retrospective study. Ethical clearance was obtained from the institute ethics committee. One hundred and fifty histopathologically proven RCC cases during the period of January 2010-September 2018 were chosen from the pathology department and corresponding blood reports were obtained from the medical records department. We divided the cases based on their staging and grading. NLR/PLR values were calculated using formulas. Statistical analysis was done using R software. Data were expressed as mean ± standard deviation, median, and percentage. Independent t-test, Mann-Whitney test, and Chi-square test were used. P < 0.05 was considered statistically significant. The receiver operating characteristic curve (ROC) was plotted to assess the sensitivity of NLR/PLR. The elevated NLR/PLR values showed a significant relation with high-grade and advanced stage RCC. The ROC curve proved the accuracy of NLR/PLR in the advanced stage and high-grade RCC. A multicentric, prospective study can be planned in the future. Follow-up studies are needed to assess their prognostic role. NLR/PLR values can become part of routine investigations for all RCC patients. The values may help to estimate pathological outcomes, chance of recovery, recurrence, and survival rates.

Adjuvant immunotherapy for renal cell carcinoma

Nephrectomy, partial or radical, remains the primary treatment for renal cell carcinoma. However, recurrence or distant metastases develop in 25–40% of patients. Higher Eastern Cooperative Oncology Group performance status, greater tumour size at diagnosis, higher tumour grade, node positivity, and sarcomatoid features are all associated with poor outcomes, 1 Volpe A Patard JJ Prognostic factors in renal cell carcinoma. World J Urol. 2010; 28: 319-327 Crossref PubMed Scopus (126) Google Scholar and patients with risk factors for disease recurrence need treatment in addition to nephrectomy to decrease their recurrence risk and improve survival. Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for clear cell renal cell carcinoma (KEYNOTE-564): 30-month follow-up analysis of a multicentre, randomised, double-blind, placebo-controlled, phase 3 trialUpdated results from KEYNOTE-564 support the use of adjuvant pembrolizumab monotherapy as a standard of care for participants with renal cell carcinoma with an increased risk of recurrence after nephrectomy. Full-Text PDF Open Access

Association between cannabis use with urological cancers: A population-based cohort study and a mendelian randomization study in the UK biobank.

Legislation of cannabis use has been approved in many European and North American countries. Its impact on urological cancers is unclear. This study was conducted to explore the association between cannabis use and the risk of urological cancers. We identified 151,945 individuals with information on cannabis use in the UK Biobank from 2006 to 2010. Crude and age-standardized incidence ratios of different urological cancers were evaluated in the entire cohort and subgroups. Cox regression was performed for survival analysis. Previous use of cannabis was a significant protective factor for renal cell carcinoma (HR=0.61, 95%CI:0.40-0.93, p=0.021) and prostate cancer (HR=0.82, 95%CI:0.73-0.93, p=0.002) in multivariable analysis. The association between previous cannabis use and both renal cell carcinoma and bladder cancer was only observed in females (HRRCC =0.42, 95%CI:0.19-0.94, p=0.034; HRBCa =0.43, 95%CI:0.21-0.86, p=0.018) but not in men. There was no significant association between cannabis use and testicular cancer incidence. Mendelian randomization demonstrated a potential causal effect of cannabis use on a lower incidence of renal cell carcinoma. Previous use of cannabis was associated with a lower risk of bladder cancer, renal cell carcinoma, and prostate cancer. The inverse association between cannabis and both renal cell carcinoma and bladder cancer was only found in females but not in males.

Prognostic nutritional index as a prognostic factor for renal cell carcinoma: A systematic review and meta-analysis.

Prognostic nutritional index (PNI) is a simple parameter which reflects patient's nutritional and inflammatory status and reported as a prognostic factor for renal cell carcinoma (RCC). Studies were included from database inception until February 2, 2022. The aim of this study is to evaluate prognostic value of PNI by meta-analysis of the diagnostic test accuracy in RCC. Studies were retrieved from PubMed, Cochrane, and EMBASE databases and assessed sensitivity, specificity, summary receiver operating characteristic curve (SROC) and area under curve (AUC). Totally, we identified 11 studies with a total of 7,296 patients were included to evaluate the prognostic value of PNI in RCC finally. They indicated a pooled sensitivity of 0.733 (95% CI, 0.651-0.802), specificity of 0.615 (95% CI, 0.528-0.695), diagnostic odds ratio (DOR) of 4.382 (95% CI, 3.148-6.101) and AUC of 0.72 (95% CI, 0.68-0.76). Heterogeneity was significant and univariate meta-regression revealed that metastasis and cut-off value of PNI might be the potential source of heterogeneity. Multivariate meta-regression analysis also demonstrated that metastasis might be the source of heterogeneity. PNI demonstrated a good diagnostic accuracy as a prognostic factor for RCC and especially in case of metastatic RCC.

Impact of the neutrophil-to-lymphocyte ratio as a surgical prognostic factor in renal cell carcinoma with inferior-vena-cava tumor thrombus

BackgroundThe aim of this study is to evaluate the efficacy of radical nephrectomy with thrombectomy and to identify the prognostic factors for patients with renal cell carcinoma (RCC) and inferior vena cava tumor thrombus (IVCTT). The role of the neutrophil-to-lymphocyte ratio (NLR), which has been reported to be a useful prognostic predictor for various solid cancers, was also investigated. MethodsFifty-five patients with RCC and IVCTT who underwent radical nephrectomy and thrombectomy in our hospital were retrospectively analyzed. The relationship between clinical characteristics and surgical outcome was examined using the Kaplan–Meier method. Univariate and multivariate analyses were carried out to determine the prognostic factors. ResultsThe median follow-up time after surgery was 44.2 months. Twenty-seven patients died of RCC, and 4 died of other disease at last follow-up. There were no patients with postoperative pulmonary embolism (PE) or deaths from PE. The median cancer-specific survival (CSS) and overall survival (OS) were 81.0 (95% confidence interval [CI]: 42.0–103.2) and 69.0 (95% CI: 34.3–81.5) months, respectively. Significant prognostic factors for CSS were distant metastasis (p = 0.045) and NLR ≥ 2.9 (p = 0.009). The only independent predictor for OS was the NLR ≥ 2.9 (p = 0.034). ConclusionsA high preoperative NLR level was an independent poor prognostic factor influencing CSS and OS of patients with RCC and IVCTT who underwent radical nephrectomy and thrombectomy. The NLR may be an available biomarker that helps with preoperative risk stratification.

A meta-analysis of the platelet-lymphocyte ratio: A notable prognostic factor in renal cell carcinoma.

The platelet-lymphocyte ratio (PLR) has been assessed in some studies on renal cell carcinoma (RCC), but the results have been inconsistent. This meta-analysis aims to review and report the latest data regarding the prognostic role of the PLR in RCC patients. Articles were searched in the PubMed, EMBASE, and Cochrane Library electronic databases. Studies were filtered according to a selection strategy, and data corresponding to the index of interest were extracted. A fixed-effects model or random-effects model was selected based on heterogeneity. The sensitivity analysis was carried out by eliminating the studies one by one. Finally, funnel plots and Egger's test were used to assess publication bias, and the trim and fill method was used to assess the impact of bias on the results. In total, 15,193 patients with RCC from 44 studies were included in this meta-analysis. The pooled analysis indicated that the higher the PLR was, the poorer the prognosis for RCC patients in terms of overall survival (hazard ratio (HR) = 1.01 (95% confidence interval (CI) 1.00, 1.02), P = 0.010), cancer-special survival (CSS) (HR = 1.21 (95% CI 1.00, 1.46), P = 0.05), progression-free survival (HR = 1.44 (95% CI 1.28, 1.62), P < 0.00001), recurrence-free survival (HR = 1.73 (95% CI 1.11, 2.71), P = 0.02), disease-free survival (HR = 1.63 (95% CI 0.91, 2.94), P = 0.01) and metastasis-free survival (HR = 1.223 (95% CI 0.712, 2.099), P = 0.466). In the subgroup analysis of high PLR, targeted treatment, TKI use, nivolumab use, surgical treatment, clear cell RCC, metastasis, Asian race, and high PLR were related to poor prognosis. This study showed that a high PLR was associated with the poor prognosis of RCC patients, but more studies are needed to confirm the value of the PLR.

Design on Early Warning System for Renal Cancer Recurrence Based on CNN-Based Internet of Things

Kidney cancer is a type of urinary system tumor. The incidence of kidney cancer, which is second only to bladder cancer, has shown an overall upward trend in recent years. However, the early judgment of kidney cancer is still in the imaging biomarker discovery stage. Early detection and treatment cannot be achieved. Based on the natural advantages of the Internet of Things in the medical field, we focused on an intelligent early warning model of renal cancer recurrence and built a renal cancer early warning system integrated with the Internet of Things. We integrated the influencing factors of renal cell carcinoma, constructed a sample set, conducted data analysis and optimized the dataset. Aiming at the instability of renal cancer recurrence, five supervised learning prediction algorithms, including multiple linear regression, Bayesian ridge regression, gradient boosting tree, support vector regression, and convolutional neural network were used to develop a renal cancer recurrence prediction model. The predictive performance of these five algorithms were compared and discussed. Finally, the best renal cancer recurrence prediction model was established by combining a convolutional neural network with an Internet of Things medical framework. This design provided an intelligent early warning system to predict the recurrence time of renal cancer patients. In addition, the warning prompts provided in accordance with the model results can assist doctors in making preliminary judgments of the patient&#x2019;s condition and has a certain auxiliary effect on the clinical diagnosis and treatment of cancer and kidney cancers.

The study of immunohistochemical expression of vascular endothelial growth factor in renal-cell carcinoma

ObjectiveTo study immunohistochemical expression of vascular endothelial growth factor (VEGF) renal-cell carcinoma (RCC) and correlate its expression with the studied clinicopathologic parameters.BackgroundRCC is the sixth diagnosed cancer in males and the tenth in females accounting for 5 and 3% of cancer incidence, respectively. VEGF is a peptide with angiogenic properties. It is thought to have an important role in RCC development and progression.Patients and methodsThis retrospective study was performed on 58 cases of RCC and 31 cases of nonneoplastic kidney tissue. The slides were subjected to VEGF immunohistochemical staining using a streptavidin–biotin–peroxidase technique. The relationships between VEGF expression in RCC cases and nonneoplastic cases, as well as correlation between VEGF expression and clinicopathological parameters in RCC cases, were statistically analyzed.ResultsVEGF showed low expression in 27.6% and high expression in 72.4% of RCC cases versus 48.4 and 51.6% in nonneoplastic cases, respectively. Higher VEGF expression was correlated with female sex, left-sided tumors, low tumor-infiltrating lymphocytes, and higher-grade tumors.ConclusionHigher VEGF expression is correlated with RCC development and may be an indicator of poor outcome in RCC patients.

M2 macrophages secrete CXCL13 to promote renal cell carcinoma migration, invasion, and EMT

ObjectiveM2 macrophages are associated with a poor prognosis in a variety of malignancies. There are, however, few relevant investigations in clear cell renal cell carcinoma (ccRCC).MethodsThe expression of M2 macrophages in ccRCC tissues was first discovered using immunohistochemistry in this study. Then, M2 macrophages were created in vitro to see how they affected the proliferation, migration, invasion, and EMT of ccRCC cells. Using qPCR and prognostic analysis identifies important chemokine. Antibody neutralization tests confirmed the chemokine’s involvement and function. Pathway inhibitors confirmed the main pathway of M2 macrophages in ccRCC. Finally, qPCR and IHC were used to confirm the expression of chemokine receptors in ccRCC tissues.ResultsThe presence of M2 macrophages was linked to a poor outcome in ccRCC. M2 macrophages enhanced the proliferation, migration, invasion, and EMT of ccRCC lines in vitro. CXCL13 was identified as the main chemokine by prognostic analysis and qPCR tests. CXCL13 neutralizing antibodies can inhibit the stimulation of M2 macrophages in ccRCC lines’ proliferation, migration, invasion, and EMT. M2 macrophages and CXCL13 may activate the Akt pathway in ccRCC lines, and Akt inhibitors decrease ccRCC lines proliferation, migration, invasion, and EMT. CXCR5 expression is a poor prognostic factor for renal cell carcinoma, according to qPCR and immunohistochemistry. In vivo experiments further proved that CXCL13 secreted by M2 macrophages can promote tumor proliferation.ConclusionsM2 macrophages in the immunological milieu secrete CXCL13, which promotes ccRCC proliferation, migration, invasion, and EMT. Our findings contribute to a better understanding of the function of the tumor microenvironment in the incidence and progression of ccRCC, and they may point to novel therapeutic targets for ccRCC.

GPNMB overexpression is associated with extensive bone metastasis and poor prognosis in renal cell carcinoma

Glycoprotein non-metastatic protein B (GPNMB) promotes bone metastasis (BM) in various types of cancer. However, GPNMB expression and its function in patients with renal cell carcinoma (RCC) and BM is still unknown. Therefore, the clinical significance of GPNMB and its biological function in RCC with BM was investigated in the present study. A total of 31 patients with RCC and BM were retrospectively collected. The association between GPNMB protein expression level on the primary tumor and the clinicopathological characteristics of the patients was analyzed. Kaplan-Meier analysis was used to investigate the association between GPNMB expression and the prognosis of the patients. The effects of GPNMB inhibition on cell proliferation, migration and invasion in RCC cells were investigated using short hairpin (sh)RNA. High GPNMB expression level was significantly associated with the number (P=0.001) and the extent of BM (P=0.001), Fuhrman grade (P=0.037), and ERK expression level (P=0.003) of the primary tumor. In addition, GPNMB overexpression was significantly associated with poor prognosis with respect to overall survival time (P=0.001). Furthermore, a specific shRNA sequence targeting the GPNMB gene was constructed and transduced into the ACHN cell line, using a lentivirus vector to obtain a stable cell line with low mRNA expression level of GPNMB. Low GPNMB expression level inhibited RCC cell proliferation, which was measured using a Cell Counting Kit-8 assay. Cell migration and invasion ability was significantly decreased in GPNMB knockdown RCC cells compared with that in cells transduced with the negative control shRNA. In addition, the protein expression levels of phosphorylated ERK were lower in the GPNMB shRNA-transduced ACHN cells compared with those in the control cells. Therefore, these results suggested that GPNMB plays an important role in tumor progression in RCC with BM. Furthermore, it might serve as a predictive marker for BM and as a poor prognostic factor in RCC with BM. GPNMB downregulation suppressed the proliferation, migration and invasion of the RCC cells, which may be mediated through the inhibition of the ERK signaling pathway.

Clinicopathological and Preclinical Patient-Derived Model Studies Define High Expression of NRN1 as a Diagnostic and Therapeutic Target for Clear Cell Renal Cell Carcinoma

BackgroundAcquired therapeutic resistance and metastasis/recurrence remain significant challenge in advance renal cell carcinoma (RCC), thus the establishment of patient-derived cancer models may provide a clue to assess the problem. We recently characterized that neuritogenesis-related protein neuritin 1 (NRN1) functions as an oncogene in testicular germ cell tumor. This study aims to elucidate the role of NRN1 in RCC.MethodsNRN1 expression in clinical RCC specimens was analyzed based on immunohistochemistry. NRN1-associated genes in RCC were screened by the RNA-sequencing dataset from The Cancer Genome Atlas (TCGA). RCC patient-derived cancer cell (RCC-PDC) spheroid cultures were established and their viabilities were evaluated under the condition of gene silencing/overexpression. The therapeutic effect of NRN1-specific siRNA was evaluated in RCC-PDC xenograft models.ResultsNRN1 immunoreactivity was positively associated with shorter overall survival in RCC patients. In TCGA RCC RNA-sequencing dataset, C-X-C chemokine receptor type 4 (CXCR4), a prognostic and stemness-related factor in RCC, is a gene whose expression is substantially correlated with NRN1 expression. Gain- and loss-of-function studies in RCC-PDC spheroid cultures revealed that NRN1 significantly promotes cell viability along with the upregulation of CXCR4. The NRN1-specific siRNA injection significantly suppressed the proliferation of RCC-PDC-derived xenograft tumors, in which CXCR4 expression is significantly repressed.ConclusionNRN1 can be a potential diagnostic and therapeutic target in RCC as analyzed by preclinical patient-derived cancer models and clinicopathological studies.

PD40-02 TIM3 EXPRESSION ON TUMOR CELLS PREDICTS RESPONSE TO ANTI-PD-1 THERAPY FOR RENAL CANCER

You have accessJournal of UrologyKidney Cancer: Advanced (including Drug Therapy) II (PD40)1 Sep 2021PD40-02 TIM3 EXPRESSION ON TUMOR CELLS PREDICTS RESPONSE TO ANTI-PD-1 THERAPY FOR RENAL CANCER Renpei Kato, Takashi Tuyukubo, Daiki Ikarashi, Tomohiko Matsuura, Shigekatsu Maekawa, Yoichiro Kato, Mitsugu Kanehira, Ryo Takata, Kazuyuki Ishida, and Wataru Obara Renpei KatoRenpei Kato More articles by this author , Takashi TuyukuboTakashi Tuyukubo More articles by this author , Daiki IkarashiDaiki Ikarashi More articles by this author , Tomohiko MatsuuraTomohiko Matsuura More articles by this author , Shigekatsu MaekawaShigekatsu Maekawa More articles by this author , Yoichiro KatoYoichiro Kato More articles by this author , Mitsugu KanehiraMitsugu Kanehira More articles by this author , Ryo TakataRyo Takata More articles by this author , Kazuyuki IshidaKazuyuki Ishida More articles by this author , and Wataru ObaraWataru Obara More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002050.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: This study aimed to identify novel prognostic biomarker for advanced renal cell carcinoma (RCC) patients treated with anti-PD-1 therapy, using quantitative multi-immunofluorescence (IF) analysis of tumor immunity. METHODS: Twenty-five consecutive patients who had metastatic or unresectable RCC treated with anti-PD-1 therapy were studied. The patients were divided into a responder group (n=12) and a non-responder group (n=13). Quantitative multi-IF staining was performed on biopsy or surgical kidney samples using a panel of antibodies. Sections were scanned using a Mantra microscope, and the images were analyzed with inFormTM software. RESULTS: Responders had significantly higher rate of TIM3-positive tumor (100% versus 53.9%, p <0.01) than non-responders. Multi-IF analysis showed that TIM3 expression on tumor cells was most strongly related to response to anti-PD-1 therapy, while some of the known immune-related prognostic factors in RCC (CD45RO, FOXP3, VEGF, PD-L1, PD-L2, CD163) had no significant association. Patients with TIM3-positive tumor showed significantly longer overall survival (not reached median time versus 6.0 months, p <0.01) and progression-free survival (18.9 versus 1.1 months, p <0.01) than those with TIM3-negative tumor. Immunohistochemistry study using samples obtained after anti-PD-1 therapy showed infiltration of CD163 macrophages and release of HMGB1, a ligand of TIM3, in necrotic tumor area. CONCLUSIONS: Our study found clinical correlation between TIM3 expression on tumor cells and response to anti-PD-1 therapy. Further studies are warranted to verify whether TIM3 expression on tumor cells before systemic therapy predicts the efficacy of anti-PD-1 therapy for RCC in the clinical setting. Source of Funding: None of the funding sources had any role in the study © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e674-e674 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Renpei Kato More articles by this author Takashi Tuyukubo More articles by this author Daiki Ikarashi More articles by this author Tomohiko Matsuura More articles by this author Shigekatsu Maekawa More articles by this author Yoichiro Kato More articles by this author Mitsugu Kanehira More articles by this author Ryo Takata More articles by this author Kazuyuki Ishida More articles by this author Wataru Obara More articles by this author Expand All Advertisement Loading ...

PD-L1 Expression and Clinicopathological Factors in Renal Cell Carcinoma: A Comparison of Antibody Clone 73-10 With Clone 28-8

Expression of programmed death ligand-1 (PD-L1) is associated with poor prognosis in renal cell carcinoma (RCC). Although a new antibody clone for immunohistochemical assay, 73-10, has shown greater sensitivity than other assays (28-8, 22C3, SP142, and SP263) in non-small cell lung cancer, PD-L1 expression using 73-10 has never been assessed in RCC. Therefore, this study aimed to evaluate the association of clinicopathological factors with PD-L1 expression detected by clone 73-10 and compare it with that detected by 28-8. Tissue microarray samples from 582 patients who underwent radical or partial nephrectomy for RCC were immunohistochemically assessed using clones 73-10 and 28-8. The positivity for PD-L1 expression in RCC by 73-10 was higher than that of 28-8 and significantly associated with worse pathological factors and a higher risk of cancer-specific mortality. Positivity for PD-L1 expression by 73-10, as compared to 28-8, was associated with worse clinicopathological factors and prognosis for patients with RCC.

Impact of Body Mass Index on Survival of Metastatic Renal Cancer.

Obesity has been established as a risk factor for renal cell carcinoma (RCC). Recently, studies have described obesity as a probable protecting factor in the metastatic stage of RCC. In this study, we assessed the relationship between body mass index (BMI) and overall survival in patients under systemic therapy.The correlation between BMI and overall median survival was studied in 76 patients diagnosed with metastatic RCC under systemic therapy. The groups were divided into overweight and obesity (BMI > 25 kg/m2) and underweight or normal (BMI < 25 kg/m2). Statistical analysis was performed using the Cox regression model adjusted by gender.A total of 76 patients were studied: 16 women (21%) and 60 men (79%). The median BMI was 27.96 kg/m2; 24 patients (31.6%) had low BMI and 52 (68.4%) had high BMI. Median overall survival in the group with BMI > 25 kg/m2 was 17 months (95% confidence interval [CI]: 13–34 months), while in the group with BMI ≤ 25 kg/m2, it was 14 months (95% CI: 8–20 months). When adjusted by gender, the group with BMI > 25 kg/m2 presented a hazards ratio of 0.54 (95% CI: 0.30–0.96), P = 0.044 (Log Rank).A high BMI significantly acts as a protecting factor. We observed an increased overall survival of overweight and obese patients within the context of metastatic RCC under systemic treatment. These data confirm the findings published in other studies that suggest the role of lipid metabolism in this type of tumors.

A novel Apigenin derivative suppresses renal cell carcinoma via directly inhibiting wild-type and mutant MET

MET, the receptor of hepatocyte growth factor (HGF), is a driving factor in renal cell carcinoma (RCC) and also a proven drug target for cancer treatment. To improve the activity and to investigate the mechanisms of action of Apigenin (APG), novel derivatives of APG with improved properties were synthesized and their activities against Caki-1 human renal cancer cell line were evaluated. It was found that compound 15e exhibited excellent potency against the growth of multiple RCC cell lines including Caki-1, Caki-2 and ACHN and is superior to APG and Crizotinib. Subsequent investigations demonstrated that compound 15e can inhibit Caki-1 cell proliferation, migration and invasion. Mechanistically, 15e directly targeted the MET kinase domain, decreased its auto-phosphorylation at Y1234/Y1235 and inhibited its kinase activity and downstream signaling. Importantly, 15e had inhibitory activity against mutant MET V1238I and Y1248H which were resistant to approved MET inhibitors Cabozantinib, Crizotinib or Capmatinib. In vivo tumor graft study confirmed that 15e repressed RCC growth through inhibition of MET activation. These results indicate that compound 15e has the potential to be developed as a treatment for RCC, and especially against drug-resistant MET mutations.