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https://www.readbyqxmd.com/read/29050224/secreted-mir-210-3p-as-non-invasive-biomarker-in-clear-cell-renal-cell-carcinoma
#1
Vincenzo Petrozza, Antonio Luigi Pastore, Giovanni Palleschi, Claudia Tito, Natale Porta, Serena Ricci, Chiara Marigliano, Manuela Costantini, Giuseppe Simone, Angelina Di Carlo, Michele Gallucci, Antonio Carbone, Francesco Fazi
The most common subtype of renal cell carcinoma (RCC) is clear cell RCC (ccRCC). It accounts for 70-80% of all renal malignancies representing the third most common urological cancer after prostate and bladder cancer. The identification of non-invasive biomarkers for the diagnosis and responsiveness to therapy of ccRCC may represent a relevant step-forward in ccRCC management. The aim of this study is to evaluate whether specific miRNAs deregulated in ccRCC tissues present altered levels also in urine specimens...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29046731/promoter-methylation-inhibits-expression-of-tumor-suppressor-kibra-in-human-clear-cell-renal-cell-carcinoma
#2
Katrin Schelleckes, Boris Schmitz, Giuliano Ciarimboli, Malte Lenders, Hermann J Pavenstädt, Edwin Herrmann, Stefan-Martin Brand, Eva Brand
BACKGROUND: KIBRA has been suggested as a key regulator of the Hippo signaling pathway, regulating organ size, cell contact inhibition, tissue regeneration as well as tumorigenesis and cystogenesis. We recently reported that human KIBRA expression depends on a complex alternative CpG-rich promoter system. Our current study aimed at the identification of epigenetic mechanisms associated with alterations in KIBRA expression regulation. RESULTS: We identified two separated methylation-sensitive CpG islands located to independent KIBRA promoter regions...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/29038551/a-novel-machine-learning-approach-reveals-latent-vascular-phenotypes-predictive-of-renal-cancer-outcome
#3
Nathan Ing, Fangjin Huang, Andrew Conley, Sungyong You, Zhaoxuan Ma, Sergey Klimov, Chisato Ohe, Xiaopu Yuan, Mahul B Amin, Robert Figlin, Arkadiusz Gertych, Beatrice S Knudsen
Gene expression signatures are commonly used as predictive biomarkers, but do not capture structural features within the tissue architecture. Here we apply a 2-step machine learning framework for quantitative imaging of tumor vasculature to derive a spatially informed, prognostic gene signature. The trained algorithms classify endothelial cells and generate a vascular area mask (VAM) in H&E micrographs of clear cell renal cell carcinoma (ccRCC) cases from The Cancer Genome Atlas (TCGA). Quantification of VAMs led to the discovery of 9 vascular features (9VF) that predicted disease-free-survival in a discovery cohort (n = 64, HR = 2...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29036563/loss-of-cd15-expression-in-clear-cell-renal-cell-carcinoma-is-correlated-with-worse-prognosis-in-chinese-patients
#4
Chen-Yan Wu, Jian-Ping Huo, Xin-Ke Zhang, Yi-Jun Zhang, Wan-Ming Hu, Ping Yang, Jia-Bin Lu, Zhi-Ling Zhang, Yun Cao
Purpose: To explore the role of CD15 expression in the prognosis of clear cell renal cell carcinoma (ccRCC) in Chinese patients. Methods: The study included 301 patients who had undergone surgery for localized ccRCC. All paraffin-embedded tumor sections were collected to make a set of tissue microarrays. CD15 expression was assessed by immunohistochemistry. The relationship between CD15 expression and survival parameters, clinicopathology features was assessed. Kaplan-Meier and Cox proportional hazards model were utilized to determine the correlation between CD15 expression and overall survival (OS)...
September 21, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29033582/hif-pathway-and-c-myc-as-biomarkers-for-response-to-sunitinib-in-metastatic-clear-cell-renal-cell-carcinoma
#5
P Maroto, E Esteban, E Fernández Parra, M J Mendez-Vidal, M Domenech, B Pérez-Valderrama, V Calderero, J L Pérez-Gracia, E Grande, F Algaba
BACKGROUND: Clear-cell renal cell carcinoma (ccRCC) is a heterogeneous disease with a different clinical behavior and response to targeted therapies. Differences in hypoxia-inducible factor (HIF) expression have been used to classify von Hippel-Lindau gene (VHL)-deficient ccRCC tumors. c-Myc may be driving proliferation in HIF-2α-expressing tumors in a growth factor-independent manner. OBJECTIVE: To explore the HIF-1α, HIF-2α and c-Myc baseline expression as potential predictors of sunitinib outcome as well as the effectiveness and safety with sunitinib in patients with metastatic ccRCC in routine clinical practice...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29030639/androgen-receptor-increases-hematogenous-metastasis-yet-decreases-lymphatic-metastasis-of-renal-cell-carcinoma
#6
Qingbo Huang, Yin Sun, Xin Ma, Yu Gao, Xintao Li, Yuanjie Niu, Xu Zhang, Chawnshang Chang
Clear cell renal cell carcinoma (ccRCC) is a gender-biased tumor. Here we report that there is also a gender difference between pulmonary metastasis and lymph node metastasis showing that the androgen receptor (AR)-positive ccRCC may prefer to metastasize to lung rather than to lymph nodes. A higher AR expression increases ccRCC hematogenous metastasis yet decreases ccRCC lymphatic metastases. Mechanism dissection indicates that AR enhances miR-185-5p expression via binding to the androgen response elements located on the promoter of miR-185-5p, which suppresses VEGF-C expression via binding to its 3' UTR...
October 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29029447/the-association-between-renal-sinus-fat-area-and-the-progression-free-survival-in-chinese-non-metastatic-clear-cell-renal-cell-carcinoma-patients
#7
Haichao Huang, Shi Chen, Wei Yu, Zirong Ye, Wei Li, Jinchun Xing, Xiurong Wu
In this retrospective study, we evaluated the association between renal sinus fat area (RSFA) and survival in 268 Chinese non-metastatic clear-cell renal cell carcinoma (ccRCC) patients. Patients with high RSFA exhibited better progression-free survival than those with low RSFA in both univariable (HR: 0.240; 95% CI: 0.119-0.482; p < 0.001) and multivariable (HR: 0.432; 95% CI: 0.369-2.749; p = 0.027) analyses. A propensity-score matched (PSM) analysis using Kaplan-Meier curves confirmed our findings (log-rank test; p = 0...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029037/functional-variants-in-the-low-density-lipoprotein-receptor-gene-are-associated-with-clear-cell-renal-cell-carcinoma-susceptibility
#8
Gui-Ming Zhang, Meng-Yun Wang, Ya-Nan Liu, Yao Zhu, Fang-Ning Wan, Qing-Yi Wei, Ding-Wei Ye
Recent studies indicate that abnormal levels of low-density lipoprotein (LDL), which is an important component of dyslipidaemia, are associated with alterations to cancer risk, including that of renal cell carcinoma (RCC). Single nucleotide polymorphisms at microRNA-binding sites contribute to cancer susceptibility and progression by affecting the mRNA function of target genes. In this case-control study, we examined the frequency of six potentially functional single nucleotide polymorphisms in the LDL receptor gene (LDLR) in 1004 clear cell RCC (ccRCC) patients and 1065 cancer-free subjects...
September 22, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29021138/glutamine-addiction-in-kidney-cancer-suppresses-oxidative-stress-and-can-be-exploited-for-real-time-imaging
#9
Omran Abu Aboud, Samy Habib, Josephine F Trott, Benjamin Stewart, Sitai Liang, Abhijit J Chaudhari, Julie L Sutcliffe, Robert H Weiss
Many cancers appear to activate intrinsic antioxidant systems as a means to counteract oxidative stress. Some cancers, such as clear cell renal cell carcinoma (ccRCC), require exogenous glutamine for growth and exhibit reprogrammed glutamine metabolism, at least in part due to the glutathione pathway, an efficient cellular buffering system that counteracts reactive oxygen species (ROS) and other oxidants. We show here that ccRCC xenograft tumors under the renal capsule exhibit enhanced oxidative stress compared to adjacent normal tissue and the contralateral kidney...
October 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/28984183/xbseq2-a-fast-and-accurate-quantification-of-differential-expression-and-differential-polyadenylation
#10
Yuanhang Liu, Ping Wu, Jingqi Zhou, Teresa L Johnson-Pais, Zhao Lai, Wasim H Chowdhury, Ronald Rodriguez, Yidong Chen
BACKGROUND: RNA sequencing (RNA-seq) is a high throughput technology that profiles gene expression in a genome-wide manner. RNA-seq has been mainly used for testing differential expression (DE) of transcripts between two conditions and has recently been used for testing differential alternative polyadenylation (APA). In the past, many algorithms have been developed for detecting differentially expressed genes (DEGs) from RNA-seq experiments, including the one we developed, XBSeq, which paid special attention to the context-specific background noise that is ignored in conventional gene expression quantification and DE analysis of RNA-seq data...
October 3, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28978925/increased-expression-of-fibrinogen-like-protein-2-is-associated-with-poor-prognosis-in-patients-with-clear-cell-renal-cell-carcinoma
#11
Ming Tang, Xu Cao, Peng Li, Kun Zhang, You Li, Quan-You Zheng, Gui-Qing Li, Jian Chen, Gui-Lian Xu, Ke-Qin Zhang
Fibrinogen-like protein 2 (FGL2) is highly expressed in various tumour tissues and plays a vital role in tumour initiation and progression. This study evaluated the clinical significance of FGL2 in patients with clear cell renal cell carcinoma (ccRCC). FGL2 expression in fresh and 170 archived paraffin-embedded ccRCC tissues was measured by quantitative RT-PCR, western blotting, and immunohistochemitry. FGL2 expression was significantly upregulated in ccRCC. Statistical analyses by using Kaplan-Meier method showed that high FGL2 expression was associated with poor overall survival (OS) and recurrence-free survival (RFS) of patients with ccRCC...
October 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28978636/ezh2-modifies-sunitinib-resistance-in-renal-cell-carcinoma-by-kinome-reprogramming
#12
Remi Adelaiye-Ogala, Justin Budka, Nur P Damayanti, Justine Arrington, Mary W Ferris, Chuan-Chih Hsu, Sreenivasulu Chintala, Ashley R Orillion, Kiersten Marie Miles, Li Shen, May Elbanna, Eric Ciamporcero, Sreevani Arisa, Piergiorgio Pettazzoni, Giulio F Draetta, Mukund Seshadri, Bradley A Hancock, Milan Radovich, Janaiah Kota, Michael Buck, Heike Keilhack, Brian P McCarthy, Scott A Persohn, Paul R Territo, Yong Zang, Joseph Irudayaraj, Andy W Tao, Peter Hollenhorst, Roberto Pili
Acquired and intrinsic resistance to receptor tyrosine kinase inhibitors (RTKi) represent a major hurdle in improving the management of clear cell renal cell carcinoma (ccRCC). Recent reports suggest that drug resistance is driven by tumor adaptation via epigenetic mechanisms that activate alternative survival pathways. The histone methyl transferase EZH2 is frequently altered in many cancers including ccRCC. To evaluate its role in ccRCC resistance to RTKi, we established and characterized a spontaneously metastatic, patient-derived xenograft (PDX) model that is intrinsically resistant to the RTKI sunitinib but not to the VEGF therapeutic antibody bevacizumab...
October 4, 2017: Cancer Research
https://www.readbyqxmd.com/read/28977844/high-expression-of-fut3-is-linked-to-poor-prognosis-in-clear-cell-renal-cell-carcinoma
#13
Li Meng, Le Xu, Yuanfeng Yang, Lin Zhou, Yuan Chang, Tianming Shi, Cheng Tan, Huimin An, Yu Zhu, Jiejie Xu
BACKGROUND AND PURPOSE: Some of the fucosylation catalyzed by fucosyltransferase-III mediates the epithelial-mesenchymal transition and enhances tumor cell-macrophage signaling, which promotes malignant transforming and immune evasion. The aim of the study was to investigate the association between the expression of fucosyltransferase-III and clinical outcomes of patients with clear-cell renal cell carcinoma after surgery. RESULTS: High fucosyltransferase-III expression was associated with a greater risk of recurrence (p = 0...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28976794/multicenter-validation-of-enhancer-of-zeste-homolog-2-expression-as-an-independent-prognostic-marker-in-localized-clear-cell-renal-cell-carcinoma
#14
Thai Huu Ho, Payal Kapur, Jeanette E Eckel-Passow, Alana Christie, Richard W Joseph, Daniel J Serie, John C Cheville, R Houston Thompson, Farrah Homayoun, Vandana Panwar, James Brugarolas, Alexander S Parker
Purpose Enhancer of zeste homolog 2 (EZH2), a chromatin remodeler, is implicated in the pathogenesis of clear cell renal cell carcinoma (ccRCC). However, the effect of EZH2 on outcomes in localized ccRCC is unclear, and molecular biomarkers are not currently integrated into prognostic models or adjuvant therapy trials. Methods We performed Cox regression to evaluate the association of tumor-based EZH2 gene and protein expression with survival in three independent cohorts: a cohort from The Cancer Genome Atlas (n = 532), a cohort from University of Texas Southwestern Medical Center (n = 122), and a cohort from Mayo Clinic (n = 1,338)...
October 4, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28976497/kidney-cancer-activation-of-oncogenes-driven-by-vhl-loss-in-ccrcc
#15
Louise Stone
No abstract text is available yet for this article.
October 4, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28975890/identification-and-validation-of-novel-prognostic-markers-in-renal-cell-carcinoma
#16
Maj Rabjerg
Kidney cancer (Renal Cell Carcinoma (RCC)) is one of the most deadly malignancies due to frequent late diagnosis and poor treatment options. Histologically, RCC embraces a wide variety of different subtypes with the clear cell variant (ccRCC) being the most common, accounting for 75-90% of all RCCs. At present, the surveillance protocols for follow-up of RCC patients after radical nephrectomy are based on the American Joint Committee on Cancers (AJCC) pathological tumor-node-metastasis (TNM) classification system...
October 2017: Danish Medical Journal
https://www.readbyqxmd.com/read/28975715/data-independent-acquisition-based-quantitative-proteomic-analysis-reveals-potential-biomarkers-of-kidney-cancer
#17
Yimeng Song, Lijun Zhong, Juntuo Zhou, Min Lu, Tianying Xing, Lulin Ma, Jing Shen
PURPOSE: Renal cell carcinoma (RCC) is a malignant and metastatic cancer with 95% mortality, and clear cell RCC (ccRCC) is the most observed among the five major subtypes of RCC. Specific biomarkers that can distinguish cancer tissues from adjacent normal tissues should be developed to diagnose this disease in early stages and conduct a reliable prognostic evaluation. EXPERIMENTAL DESIGN: Data-independent acquisition (DIA) strategy has been widely employed in proteomic analysis because of various advantages, including enhanced protein coverage and reliable data acquisition...
October 4, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28975613/extracellular-vesicles-isolated-from-human-renal-cell-carcinoma-tissues-disrupt-vascular-endothelial-cell-morphology-via-azurocidin
#18
Kentaro Jingushi, Motohide Uemura, Naomi Ohnishi, Wataru Nakata, Kazutoshi Fujita, Takuya Naito, Risa Fujii, Naomi Saichi, Norio Nonomura, Kazutake Tsujikawa, Koji Ueda
Cancer-associated extracellular vesicles (EVs) are intimately involved in establishment of tumor microenvironment and occurrence of metastasis. However, previous studies have mainly relied on experiments with cultured cell lines or mouse models, making it difficult to gain a full understanding of EV functions in human body. Hence, we extracted EVs directly from surgically resected viable clear cell renal cell carcinoma (ccRCC) tissues and adjacent normal renal tissues (n = 20). Quantitative LC/MS analysis identified 3,871 tissue-exudative EV (Te-EV) proteins, among which azurocidin (AZU1) was highly enriched in tumor Te-EVs (p = 2...
October 4, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28972214/a-computational-method-using-differential-gene-expression-to-predict-altered-metabolism-of-multicellular-organisms
#19
Lvxing Zhu, Haoran Zheng, Xinying Hu, Yang Xu
Altered metabolism is often identified as a cause or an effect of physiology and pathogenesis. But it is difficult to predict the metabolic flux distributions of multicellular organisms due to the lack of an explicit metabolic objective function. Here we present a computational method which can successfully describe the differences in metabolism between two different conditions on a large scale. By integrating gene expression data with an existing comprehensive reconstruction of the global human metabolic network, we qualitatively predicted significantly differential fluxes without prior knowledge or the rate of metabolite uptake and secretion...
October 3, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28968973/mir-367-regulates-cell-proliferation-and-metastasis-by-targeting-metastasis-associated-protein-3-mta3-in-clear-cell-renal-cell-carcinoma
#20
Dexin Ding, Yue Zhang, Lin Wen, Jiangbo Fu, Xue Bai, Yuhua Fan, Yuan Lin, Hongshuang Dai, Qiang Li, Yong Zhang, Ruihua An
Clear-cell renal cell carcinoma (ccRCC) is an aggressive and malignant kidney cancer which has the worst prognosis. Although microRNAs (miRNAs) have recently been identified as a novel class of regulators in oncogenesis and metastasis, there are few studies on their participation in ccRCC. In the present study, we observed that miR-367 expression was increased in both human ccRCC tissues and cell lines. Cell proliferation was evaluated by MTT assay and 5-Ethynyl-2'-deoxyuridine (EdU) assay kit, which indicated that inhibition of miR-367 could suppress the ccRCC proliferation...
September 8, 2017: Oncotarget
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