CXC chemokine receptor 2 is associated with postoperative recurrence and survival of patients with non-metastatic clear-cell renal cell carcinoma

BackgroundAberrant CXC chemokine receptor 2 (CXCR2) expression has been shown to promote angiogenesis and proliferation in renal cell carcinoma (RCC). Our current study aims to evaluate the prognostic significance of CXCR2 in patients with non-metastatic clear-cell renal cell carcinoma (ccRCC).MethodsWe retrospectively enrolled 375 patients with non-metastatic ccRCC undergoing nephrectomy at Zhongshan Hospital, Fudan University between 2003 and 2008. The cohort was split into a training set (n = 184) and a validation set (n = 191). CXCR2 expression was assessed by immunohistochemical staining and its association with clinicopathologic features and prognosis were evaluated.ResultsCXCR2 expression was significantly associated with tumour size (P = 0.036 and P = 0.016, respectively) and Fuhrman grade (P = 0.009 and P = 0.001, respectively) in the training and validation sets. Moreover, high CXCR2 expression indicated poor overall survival (OS) (P < 0.001 and P = 0.001, respectively) and recurrence-free survival (P < 0.001 and P < 0.001, respectively) in the training and validation sets. The incorporation of CXCR2 into the T stage and Fuhrman grade would help to refine individual risk stratification. Furthermore, CXCR2 expression was identified as an independent adverse prognostic factor for survival (P < 0.001) and recurrence (P < 0.001). A predictive nomogram was generated with identified independent prognosticators to assess patient recurrence-free survival at 5 and 10 years.ConclusionsCXCR2 is a potential independent adverse prognostic biomarker for recurrence and survival of patients with non-metastatic ccRCC after nephrectomy.     

Identification of international metastatic renal cell carcinoma database consortium (IMDC) intermediate-risk subgroups in patients with metastatic clear-cell renal cell carcinoma

Majority of patients with clear-cell renal cell carcinoma (ccRCC) at first line (1L) treatment are classified in the intermediate-risk (IR) subgroup according to International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score. As these patients have different prognosis, the aim of this study is to better characterize IR patients in order to better tailor the treatment. Retrospective analysis was performed from IGReCC (Institut Gustave Roussy Renal Cell Carcinoma) database. Overall survival (OS) was defined from start of 1L therapy to death or last follow-up. A multivariable Cox model with backward selection procedure (α = 0.01) and a Classification and Regression Tree (CART) analysis were performed to identify which prognostic factors were associated to OS in IR patients.From 2005 to 2017, 777 patients with ccRCC were treated with an anti-VEGF 1L therapy. Among 571 evaluable patients for IMDC score, 290 (51%) were classified as IR. With median follow-up 5.8 years (min: 0, max: 12.4) 212 deaths (73%) were observed and median OS was 25 months. Only platelet count was significantly associated to OS (hazard ratio 1.88 [95% CI 1.27–2.88] p = 0.0017). Median OS for patients with PLT > UNL was 18 months [95% CI 12–23] versus 29 months [95% CI 21.4–35.7] for patients with normal PLT count. The selection of PLT count was confirmed on bootstrap samples and was also selected for the first split of the CART-tree analysis.Patients in the IR group have a heterogeneous prognosis. Elevated PLT count seems identifies a subgroup of patients with poor outcome in the IMDC intermediate-risk population with ccRCC.     

Prognostic factors for survival in 1059 patients treated with sunitinib for metastatic renal cell carcinoma

Background:

Prognostic factors for progression-free survival (PFS), overall survival (OS), and long-term OS (⩾30 months) were investigated in sunitinib-treated patients with metastatic renal cell carcinoma (RCC).

Methods:

Data were pooled from 1059 patients in six trials. Baseline variables, including ethnicity, were analysed for prognostic significance by Cox proportional-hazards model.

Results:

Median PFS and OS were 9.7 and 23.4 months, respectively. Multivariate analysis of PFS and OS identified independent predictors, including ethnic origin, Eastern Cooperative Oncology Group performance status, time from diagnosis to treatment, prior cytokine use, haemoglobin, lactate dehydrogenase, corrected calcium, neutrophils, platelets, and bone metastases (OS only). Characteristics of long-term survivors (n=215, 20%) differed from those of non-long-term survivors; independent predictors of long-term OS included ethnic origin, bone metastases, and corrected calcium. There were no differences in PFS (10.5 vs 7.2 months; P=0.1006) or OS (23.8 vs 21.4 months; P=0.2135) in white vs Asian patients; however, there were significant differences in PFS (10.5 vs 5.7 months; P<0.001) and OS (23.8 vs 17.4 months; P=0.0319) in white vs non-white, non-Asian patients.

Conclusion:

These analyses identified risk factors to survival with sunitinib, including potential ethnic-based differences, and validated risk factors previously reported in advanced RCC.     

Sex and the clinical value of body mass index in patients with clear cell renal cell carcinoma

Background:

An increased body mass index (BMI) is significantly associated with favourable prognosis in renal cell carcinoma (RCC). This study investigated the associations among sex, BMI, and prognosis in clear cell RCC patients.

Methods:

We retrospectively analysed 435 patients with clear cell RCC who underwent a nephrectomy. The associations among sex, BMI, clinicopathologic factors, and cancer-specific survival (CSS) were analysed.

Results:

As a continuous variable, increased BMI was associated with higher CSS rate by univariate analysis in the whole population (hazard ratio, 0.888 per kg m^–2; 95% confidence interval, 0.803–0.982; P=0.021). A sub-population analysis by sex demonstrated that BMI was significantly associated with CSS in men (P=0.004) but not in women (P=0.725). Multivariate analysis revealed BMI to be an independent predictor of CSS in only men.

Conclusion:

Body mass index was significantly associated with clear cell RCC prognosis. However, the clinical value of BMI may be different between men and women.     

Smoking negatively impacts renal cell carcinoma overall and cancer-specific survival

BACKGROUND:

Tobacco use is a leading cause of premature death, yet few studies have investigated the effect of tobacco exposure on the outcome of patients with renal cell carcinoma (RCC). The authors of this report retrospectively studied the impact of smoking on clinicopathologic factors, survival outcomes, and p53 expression status in a large cohort of patients with RCC.

METHODS:

Eight hundred‐two patients (457 nonsmokers and 345 smokers) who had up to 232 months of follow‐up were compared for differences in their clinicopathologic features and survival outcomes. Immunohistochemical differences in p53 expression were correlated with smoking status.

RESULTS:

Smokers presented more commonly with pulmonary comorbidities (P < .0001) and cardiac comorbidities (P = .014) and with a worse performance status (P = .031) than nonsmokers. Smoking was associated significantly with tumor multifocality (P = .022), higher pathologic tumor classification (P = .037), an increased risk of bulky lymph node metastases (P = .031), and the presence of distant metastases (P < .0001), especially lung metastases (P < .0001). Both overall survival (OS) (62.37 months vs 43.64 months; P = .001) and cancer‐specific survival (CSS) (87.43 months vs 56.57 months; P = .005) were significantly worse in patients who smoked. The number of pack‐years was retained as an independent predictor of CSS and OS in patients with nonmetastatic disease. Mean expression levels of p53 were significantly higher in current smokers compared with former smokers and nonsmokers (P = .012).

CONCLUSIONS:

In patients with RCC, a history of smoking was associated with worse pathologic features and survival outcomes and with an increased risk of having mutated p53. Further investigation of the genetic and molecular mechanisms associated with decreased CSS in patients with RCC who have a history of smoking is indicated. Cancer 2012;. © 2011 American Cancer Society.     

P2X7 receptor predicts postoperative cancer‐specific survival of patients with clear‐cell renal cell carcinoma

The P2X7 receptor, an ATP‐gated plasma membrane ion channel, is involved in inflammation, apoptosis and cell proliferation, and thereby plays a crucial role during oncogenic transformation in various malignancies. This study aims to evaluate the impact of P2X7 receptor expression on postoperative cancer‐specific survival of patients with clear‐cell renal cell carcinoma (ccRCC). A total of 273 patients with ccRCC undergoing nephrectomy at a single institution were retrospectively enrolled in this study, among which 86 patients died of this disease and six patients died of other causes. Clinicopathologic features and cancer‐specific survival (CSS) were recorded. P2X7 expression was assessed by immunohistochemistry in clinical specimens. Kaplan–Meier method with log rank test was performed to compare survival curves. Cox regression models were used to evaluate the prognostic values of variables on CSS. Concordance index was calculated to assess prognostic accuracy of prognostic models. Median follow‐up period was 90 months (range, 11–120 months). Intratumoral P2X7 expression was significantly lower than peritumoral tissues (P < 0.001). Moreover, high intratumoral P2X7 expression, which was significantly associated with shorten CSS (P < 0.001), high TNM stage (P = 0.038), Fuhrman grade (P = 0.035), SSIGN (stage, size, grade, and necrosis) score (P = 0.021) and University of California Integrated Staging System (UISS) score (P = 0.007), was indicated to be an independent prognostic factor for CSS (hazard ratio [HR], 1.693; P = 0.034). The prognostic accuracy of TNM stage, UISS and SSIGN scoring models was improved when intratumoral P2X7 expression was added. Intratumoral P2X7 expression is a potential independent adverse prognostic indicator for postoperative CSS of patients with ccRCC.     

Clinical outcomes and prognostic factors following the surgical resection of renal cell carcinoma spinal metastases

The efficacy of surgical resection in metastatic renal cell carcinoma is an active and important research field in the postcytokine era. Bone metastases, especially in the spine, compromise patient performance status. Metastasectomy is indicated, if feasible, because it helps to achieve the best clinical outcomes possible compared with other treatments. This study examined the postoperative survival and prognostic factors in patients who underwent metastasectomy of spinal lesions. The retrospective study included 65 consecutive patients with metastatic renal cell carcinomas who were operated on by spinal metastasectomy between 1995 and 2017 at our institution. The cancer-specific survival times from the first spinal metastasectomy to death or the last follow-up (≥3 years) were determined using Kaplan-Meier analysis. Potential factors influencing survival were analyzed using Cox proportional hazard models. Planned surgical resection of all the spine tumors was achieved in all patients. Of these, 38 had complete metastasectomy of all visible metastases, including extraspinal lesions. In all patients, the estimated median cancer-specific survival time was 100 months. The 3-, 5-, and 10-year cancer-specific survival rates were 77%, 62%, and 48%, respectively. The survival times after spinal metastasectomy were similar in both cytokine and postcytokine groups. In multivariate analyses, postoperative disability, the coexistence of liver metastases, multiple spinal metastases, and incomplete metastasectomy were significant risk factors associated with short-term survival. Complete metastasectomy, including extraspinal metastases, was associated with improved cancer-specific survival. Proper patient selection and complete metastasectomy provide a better prognosis in metastatic renal cell carcinoma patients.     

The longitudinal relationship between circulating concentrations of C-reactive protein, interleukin-6 and interleukin-10 in patients undergoing resection for renal cancer

The systemic inflammatory response, as evidenced by elevated circulating concentrations of C-reactive protein, is a stage-independent prognostic factor in patients undergoing curative nephrectomy for localised renal cancer. However, it is not clear whether the systemic inflammatory response arises from the tumour per se or as a result of an impaired immune cytokine response. The aim of the present study was to examine C-reactive protein, interleukin-6 and interleukin-10 concentrations before and following curative resection of renal cancer. Sixty-four patients with malignant renal disease and 12 with benign disease, undergoing resection were studied. Preoperatively, a blood sample was collected for routine laboratory analysis with a further sample stored before analysis of interleukin-6 and interleukin-10 using an enzyme-linked immunosorbent assay (ELISA) technique. The blood sampling procedure and analyses were repeated at approximately 3 months following resection. Circulating concentrations of both interleukin-6 and interleukin (P< or =0.01) were higher and a greater proportion were elevated (P<0.05) in malignant compared with benign disease. The renal cancer patients were grouped according to whether they had evidence of a systemic inflammatory response. In the inflammatory group T stage was higher (P<0.01), both interleukin-6 and interleukin-10 concentrations were higher (P<0.001) and elevated (P<0.10) compared with the non-inflammatory group. Tumour volume was weakly correlated with C-reactive protein (r(2)=0.20, P=0.002), interleukin-6 (r(2)=0.20, P=0.002) and interleukin-10 (r(2)=0.24, P=0.001). Following nephrectomy the proportion of patients with elevated C-reactive protein, interleukin-6 and interleukin-10 concentrations did not alter significantly. An elevated preoperative C-reactive protein was associated with increased tumour stage, interleukin-6 and interleukin-10 concentrations. However, resection of the primary tumour did not appear to be associated with significant normalisation of circulating concentrations of C-reactive protein, interleukin-6 or interleukin-10. Therefore, the presence of systemic inflammatory response is unlikely to be solely be determined by the tumour itself, but may be as a result of an impaired immune cytokine response in patients with renal cancer.     

Prognostic factors associated with long-term survival in previously untreated metastatic renal cell carcinoma.

PURPOSE: To identify prognostic factors (PF) for long-term survival in metastatic renal cell carcinoma (RCC) patients. METHODS: We retrospectively reviewed a metastatic RCC database at the Cleveland Clinic Foundation consisting of 358 previously untreated patients who were enrolled in institutional review board-approved clinical trials of immunotherapy and/or chemotherapy at our institution from 1987 to 2002. In order to identify patient characteristics associated with long-term survival, we compared 226 'short-term' survivors [defined as overall survival (OS) <2 years] with 31 'long-term' survivors (OS >or=5 years). RESULTS: Using logistic regression models, four adverse PF were identified as independent predictors of long-term survival: hemoglobin less than the lower limit of normal, greater than two metastatic sites, involved kidney (left), and Eastern Cooperative Oncology Group (ECOG) performance status (PS). Using the number of poor prognostic features present, three distinct risk groups could be identified. Patients with 0 or 1 adverse prognostic feature present had an observed likelihood of long-term survival of 32% (21/66) compared with 9% (8/91) for patients with two adverse features present and only 1% (1/93) for patients with more than two adverse features. CONCLUSIONS: Independent predictors of long-term survival in previously untreated metastatic RCC include baseline hemoglobin level, number of involved sites, involved kidney, and ECOG PS. Incorporation of these factors into a simple prognostic scoring system enables three distinct groups of patients to be identified.     

Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based immunotherapy: association to objective response and survival

The aim of the present study was to analyse lymphocyte subsets in consecutive peripheral blood samples and consecutive tumour tissue core needle biopsies performed before and during interleukin-2 based immunotherapy, and to correlate the findings with objective response and survival. Twenty-six patients with metastatic renal cell carcinoma were treated with low dose s.c. interleukin-2, interferon-alpha and histamine. A total of 250 blood samples and 62 core needle biopsies from 23 and 19 of these patients, respectively, were analysed. After 2 weeks of treatment, a significant positive correlation between absolute number of peripheral blood lymphocytes (P=0.028), CD3 (P=0.017), CD57 (P=0.041) and objective response was demonstrated. There was no correlation between any peripheral blood leukocyte subsets and survival. Cytotoxicity of peripheral blood mononuclear cells was not correlated to objective response or survival. Within the tumour tissue at baseline, a significant positive correlation between CD4 (P=0.027), CD8 (P=0.028), CD57 (P=0.007) and objective response was demonstrated. After one month of immunotherapy, a significant positive correlation between intratumoral CD3 (P=0.026), CD8 (P=0.015), CD57 (P=0.009) and objective response was demonstrated. A significant positive correlation between intratumoral baseline CD4 (P=0.047), baseline CD57 (P=0.035), CD3 at one month (P=0.049) and survival was demonstrated. These data provide novel in vivo evidence of the possible contribution of lymphocyte subsets in the tumour reduction in responding patients during interleukin-2 based immunotherapy. Confirmation of the results requires further studies including a larger number of patients.     

Flow cytometric DNA analysis of interleukin-2 responsive renal cell carcinoma

Adoptive immunotherapy using interleukin-2 (IL-2) based therapy can result in marked tumor regression in some patients with metastatic renal cell carcinoma. DNA flow cytometry has not been previously studied as a predictor of outcome of this therapy. Archival paraffin embedded tumors were studied in 23 IL-2 treated patients with metastatic renal cell carcinoma. Eleven patients were complete responders (CR) and 12 were nonresponders (NR). In the CR group, 4/11 (40%) were diploid and 7/11 (60%) were aneuploid. In the NR group, 9/12 (75%) were diploid and 3/12 (25%) were aneuploid. Although there was a trend that patients with an aneuploid DNA pattern were more likely to undergo a complete response, ploidy pattern alone was not significantly predictive of response (p² = 0.10, Fischer's exact test). When combining ploidy pattern with other variables that were predictive for complete response, such as good performance status and a higher pretreatment weight, prediction of complete response was not improved by including ploidy. This preliminary report suggests that DNA ploidy does not appear to provide any additional information concerning responsiveness to IL-2 based immunotherapy beyond that obtained by performance status and pretreatment weight in this patient population. © 1993 Wiley-Liss, Inc.     

Podoplanin associates with adverse postoperative prognosis of patients with clear cell renal cell carcinoma

Podoplanin, a transmembrane sialomucin‐like glycoprotein, was recently shown to be involved in tumor progression and metastasis, and its potential role in facilitating platelet‐based tumor embolization and promigratory phenotype of cancer cells was also demonstrated. In this study, we assessed the clinical significance of tumoral podoplanin expression in 295 patients with clear cell renal cell carcinoma (ccRCC) through immunohistochemistry on tissue microarrays and analyzing the staining intensity. Univariate analysis suggested an adverse prognostic effect of high tumoral podoplanin expression on patients' overall survival (OS) and recurrence‐free survival (RFS) (P < 0.001 for both). In the multivariate analysis, high tumoral podoplanin expression (using staining intensity as either a continuous or dichotomous variable) was still an independent adverse prognostic factor for patient survival (OS, P < 0.001, RFS, P < 0.001 for continuous; OS, P < 0.001, RFS, P = 0.002 for dichotomous). Moreover, stratified analysis identified a higher prognostic power in the intermediate/high risk patient groups. After utilizing those parameters in the validated multivariate analysis, two nomograms were constructed to predict ccRCC patients' OS and RFS (c‐index 0.815 and 0.805, respectively), and performed better than existing integrated models (P < 0.001 for all comparisons). In conclusion, high tumoral podoplanin expression could independently predict an adverse clinical outcome for ccRCC patients, and it might be useful in future for clinical decision‐making and therapeutic developments.     

Prognostic factors for renal cell carcinoma: Trakya University experience from Turkey

YURUT‐CALOGLU V., CALOGLU M., KAPLAN M., OZ‐PUYAN F., KARAGOL H., IBIS K., COSAR‐ALAS R, KOCAK Z. & INCI O. (2010) European Journal of Cancer Care 19 , 656–663 Prognostic factors for renal cell carcinoma: Trakya University experience from Turkey The purpose of the present study is to evaluate the prognostic factors of patients with renal cell carcinoma. The treatment results such as distant metastasis‐free survival and overall survival of 59 previously untreated patients were retrospectively analysed. Median follow‐up was 17.5 months (3.8–88.5 months). Overall survival was 22.4 months (3–87 months). Distant metastasis developed in 35 (59%) patients. The Eastern Cooperative Oncology Group (ECOG) performance status (P= 0.022), tumour size (P= 0.025) and lymphatic invasion (P < 0.0001) were significantly effective prognostic factors for distant metastasis‐free survival on multivariate analysis. Related to overall survival, gender (P= 0.025), ECOG performance status (P= 0.027), nuclear grade (P= 0.002), tumour size (P= 0.029), T stage (P= 0.044), nodal involvement (P= 0.003), surgical margin (P= 0.046), renal sinus invasion (P < 0.0001), perineural growth (P= 0.001) and lymphatic invasion (P < 0.0001) were significant prognostic factors on univariate analysis. Gender (P= 0.008), ECOG performance status (P= 0.027), tumour size (P= 0.025) and lymphatic invasion (P < 0.0001) retained their significance on multivariate analysis. We concluded that the most important prognostic factors for patients with renal cell carcinomas are ECOG performance status, tumour size and lymphatic invasion.     

Prognostic factors after curative surgery for renal cell carcinoma: Multivariate analysis of 260 patients

Background In patients with renal cell carcinoma, curative surgery may offer a chance of survival, but a fatal outcome is not infrequent. In this study, we investigated the prognostic factors influencing survival by using both univariate and multivariate analyses. Methods To identify the important prognostic factors for long-term survival, we retrospectively studied 260 patients who received curative surgery for renal cell carcinoma between 1978 and 1995. Survival curves were calculated by the Kaplan-Meier method and statistical differences were determined by the log-rank test. Survival correlations were tested using 20 prognostic factors. Significant factors were evaluated using Cox's multivariate proportional hazard test to determine the prognostic value. Results The median follow-up period was 39 months. The overall survival rate at 1, 5, and 10 years was 98.9%, 89.8%, and 83.3%, respectively. Of the 20 prognostic factors evaluated, the log-rank test showed significant differences in patient age, body temperature, hemoglobin, ESR, α₂-globulin, CRP, fibrinogen, pathological stage, Robson's stage, T classification, N classification, pathological grade, cell type, and pattern of tumor infiltration. However, several variables (body temperature, ESR, α₂-globulin, and fibrinogen) were excluded from the multivariate analysis because more then 10% of the data were missing. Pathological stage was selected as a representative variable for stage indices (pathological stage, Robson's stage, T classification, and N classification). Using the remaining 7 variables (age, hemoglobin, CRP, pathological stage, pathological grade, cell type, and pattern of tumor infiltration), Cox's multivariate proportional hazard analysis showed that tumor stage (P=0.0496) was the most important independent prognostic factor for patient survival. Conclusions From this analysis, the pathological tumor stage was found to be the most important factor predicting long-term survival in patients who received curative surgery for renal cell carcinoma.     

Systemic inflammation score predicts postoperative prognosis of patients with clear-cell renal cell carcinoma

Background:

Growing evidence indicates that inflammation has a crucial role in the development and progression of cancer. We developed a novel systemic inflammation score (SIS) based on preoperative serum albumin and lymphocyte-to-monocyte ratio (LMR), and examined its prognostic value for patients with clear-cell renal cell carcinoma (ccRCC) after surgery.

Methods:

The study comprised 441 ccRCC patients undergoing nephrectomy between 2008 and 2009 in a single centre. The SIS was developed and its associations with clinicopathological features and overall survival (OS) were evaluated.

Results:

The SIS consisted of serum albumin and LMR that were both retained as independent indicators adjusting for other haematological and laboratory markers of systemic inflammation responses and traditional clinicopathological features. A high SIS was significantly associated with aggressive tumour behaviours and served as an independent prognostic factor of reduced OS. Furthermore, the SIS could significantly stratify patient prognosis in different tumour stages and Mayo Clinic stage, size, grade and necrosis scores. Incorporation of the SIS into a prognostic model including TNM stage, Fuhrman grade and lymphovascular invasion generated a nomogram, which predicted accurately 3- and 5-year survival for ccRCC patients.

Conclusions:

The SIS as a potentially powerful prognostic biomarker might improve traditional clinicopathological analysis to refine clinical outcome prediction for ccRCC patients after surgery.     

Measurement of progesterone receptor in human renal cell carcinoma and normal renal tissue

Progesterone receptor was measured in eight samples of renal cell carcinoma, nine samples of normal renal tissue, and one sample of melanoma tissue. Progesterone receptor was identified in all samples, with the exception of one renal cell carcinoma. Three patients, all with receptor-positive tumors, were treated with medroxyprogesterone acetate for metastatic disease. In one of these patients there was a partial objective response to treatment. Further research regarding progesterone receptor in renal cell carcinoma is indicated.     

Tumor miR‐125b predicts recurrence and survival of patients with clear‐cell renal cell carcinoma after surgical resection

The present study aims to evaluate the impact of tumor microRNA‐125b (miR‐125b) on recurrence and survival of patients with clear‐cell renal cell carcinoma (ccRCC) following surgery. We retrospectively enrolled 276 patients (200 in the training cohort and 76 in the validation cohort) with ccRCC undergoing nephrectomy at a single institution. Clinicopathologic features, cancer‐specific survival (CSS) and recurrence‐free survival (RFS) were recorded. Tumor miR‐125b levels were assessed by in situ hybridization (ISH) in specimens of patients. The Kaplan–Meier method was applied to compare survival curves. Cox regression models were used to analyze the impact of prognostic factors on CSS and RFS. A concordance index (C‐index) was calculated to assess predictive accuracy. In both cohorts, tumor miR‐125b positively correlated with Fuhrman grade. High tumor miR‐125b indicated poor survival and early recurrence for patients with ccRCC, especially with advanced stage disease. After multivariable adjustment, tumor miR‐125b was identified as an independent adverse prognostic factor for survival and recurrence. The predictive accuracy of traditional TNM and UCLA Integrated Staging System prognostic models was improved when tumor miR‐125b was added. The results showed that tumor miR‐125b is a potential independent adverse prognostic biomarker for recurrence and survival of patients with ccRCC after nephrectomy.     

MicroRNAs as prognostic molecular signatures in renal cell carcinoma: a systematic review and meta-analysis

This is a systematic review of studies investigating the prognostic value of different microRNAs (miRs) in renal cell carcinoma (RCC). Twenty-seven relevant studies were identified, with a total of 2578 subjects. We found that elevated expression of miR-21, miR-1260b, miR-210, miR-100, miR-125b, miR-221, miR-630, and miR-497 was associated with a poor prognosis in RCC patients. Conversely, decreased expression of miR-106b, miR-99a, miR-1826, miR-215, miR-217, miR-187, miR-129–3p, miR-23b, miR-27b, and miR-126 was associated with a worse prognosis. We performed meta-analyses on studies to address the prognostic value of miR-21, miR-126, miR-210, and miR-221. This revealed that elevated miR-21 expression was associated with shorter overall survival (OS; hazard ratio [HR], 2.29; 95% confidence interval [CI], 1.28–4.08), cancer specific survival (CSS; HR, 4.16; 95% CI, 2.49–6.95), and disease free survival (DFS; HR, 2.15; 95% CI, 1.16–3.98). The decreased expression of miR-126 was associated with shorter CSS (HR, 0.35; 95% CI, 0.15–0.85), OS (HR, 0.45; 95% CI, 0.30–0.69), and DFS (HR 0.30; 95% CI, 0.18–0.50). Our comprehensive systematic review reveals that miRs, especially miR-21 and miR-126, could be promising prognostic markers and useful therapeutic targets in RCC.     

NDUFA4 expression in clear cell renal cell carcinoma is predictive for cancer-specific survival

Like other cancers, renal cell carcinoma (RCC) derives the essential energy for proliferation and survival from high rates of glycolysis rather than from oxidative phosphorylation of the mitochondrial respiration pathway. NDUFA4 (NADH Dehydrogenase (Ubiquinone) 1 Alpha Subcomplex, 4) is encoding a protein belonging to the respiratory chain of mitochondria. For a better understanding of the tumor biology and for identification of a potential new biomarker, we analyzed the regulation of NDUFA4 in RCC compared to normal tissue cells. Downregulation of NDUFA4 mRNA and protein was detected in RCC compared to normal renal tissues in quantitative real-time PCR as well as in western blot and immunohistochemical staining. Histological analysis revealed higher NDUFA4 expression in the distal tubules compared to the proximal tubules and the loop of Henle. A higher molecular weight of the NDUFA4 protein was discovered in RCC samples, possibly indicating a posttranslational modification. Moreover, NDUFA4 protein expression was predictive for cancer-specific survival. Our analysis revealed a potential new biomarker, but future studies are warranted to investigate the prognostic value of NDUF4A expression.