A Specific Gene Expression Signature Characterizes Metastatic Potential in Clear Cell Renal Cell Carcinoma

Sanjmyatav, Jimsgene; Steiner, Thomas; Wunderlich, Heiko; Diegmann, Julia; Gajda, Mieczysław; Junker, Kerstin

doi:10.1016/j.juro.2011.03.033

Cited by 37 publications

(25 citation statements)

References 29 publications

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“…3C). Significant underexpression of NFKBIA/IKBa, an inhibitor of NF-kB, harbored in the frequently lost 14q region, was able to discriminate metastatic ccRCCs from nonmetastatic tumors in a previous study (48), suggesting deletion and subsequent underexpression of NFKBIA to be indicative of metastatic potential in ccRCCs. A recent study associated deletions and low expression of NFKBIA with resistance to treatment and worse survival in glioblastomas (49).…”

Section: Discussionmentioning

confidence: 73%

Multilevel Whole-Genome Analysis Reveals Candidate Biomarkers in Clear Cell Renal Cell Carcinoma

et al. 2012

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Renal cell carcinoma (RCC) is the most common neoplasm of the kidney. We conducted an integrated analysis of copy number, gene expression (mRNA and miRNA), protein expression, and methylation changes in clear cell renal cell carcinoma (ccRCC). We used a stepwise approach to identify the most significant copy number aberrations (CNA) and identified regions of peak and broad copy number gain and loss, including peak gains (3q21, 5q32, 5q34-q35, 7p11, 7q21, 8q24, 11q13, and 12q14) and deletions (1p36, 2q34-q37, 3p25, 4q33-q35, 6q23-q27, and 9p21). These regions harbor novel tumor-related genes and miRNAs not previously reported in renal carcinoma. Integration of genome-wide expression data and gene set enrichment analysis revealed 75 gene sets significantly altered in tumors with CNAs compared with tumors without aberration. We also identified genes located in peak CNAs with concordant methylation changes (hypomethylated in copy number gains such as STC2 and CCND1 and hypermethylated in deletions such as CLCNKB, VHL, and CDKN2A/2B). For other genes, such as CA9, expression represents the net outcome of opposing forces (deletion and hypomethylation) that also significantly influences patient survival. We also validated the prognostic value of miRNA let-7i in RCCs. miR-138, located in chromosome 3p deletion, was also found to have suppressive effects on tumor proliferation and migration abilities. Our findings provide a significant advance in the delineation of the ccRCC genome by better defining the impact of CNAs in conjunction with methylation changes on the expression of cancer-related genes, miRNAs, and proteins and their influence on patient survival. Cancer Res; 72(20); 5273-84. Ó2012 AACR.

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Section: Discussionmentioning

confidence: 73%

Multilevel Whole-Genome Analysis Reveals Candidate Biomarkers in Clear Cell Renal Cell Carcinoma

et al. 2012

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“…Biomarker role. Microarray analysis of renal cell carcinoma showed an over-expression of MMP-16 in metastatic primary tumors, suggesting that MMP-16 is one of the potential biomarker for metastatic clear cell renal cell carcinoma (Sanjmyatav et al, 2011).…”

Section: Neoplastic Diseasesmentioning

confidence: 99%

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Sbardella

Fasciglione

Gioia

et al. 2012

Molecular Aspects of Medicine

209

212

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a b s t r a c tHuman matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn 2+ atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes.

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“…MMP16 not only activates pro-MMP2 by proteolytic cleavage, but is also known to degrade ECM proteins, especially basement membrane components, which facilitates cancer cell migration and tumor spreading (36). Although MMP16 protein has not been previously analyzed in endometrial tumors, its overexpression has been associated with malignant behavior and poor prognosis in numerous human malignancies, including colorectal cancer, gastric cancer, hepatocellular carcinoma, melanoma and renal cell carcinoma (36)(37)(38)(39)(40)(41). For instance, MMP16 has been reported as a β-catenin target gene in human gastric cancer, which induction is relevant for the Wnt-mediated invasion and metastasis in gastric cancer cells (38).…”

Section: Discussionmentioning

confidence: 99%

Post-transcriptional Regulation of MMP16 and TIMP2 Expression via miR-382, miR-410 and miR-200b in Endometrial Cancer

Rak

Mehlich

Garbicz

et al. 2017

CGP

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A Specific Gene Expression Signature Characterizes Metastatic Potential in Clear Cell Renal Cell Carcinoma

Abstract: We determined a metastatic signature of clear cell renal cell carcinoma by microarray analysis. Our data provide the possibility of defining the metastatic potential of primary clear cell renal cell carcinoma based on a select number of genes even in a localized situation.

Cited by 37 publications

References 29 publications

Multilevel Whole-Genome Analysis Reveals Candidate Biomarkers in Clear Cell Renal Cell Carcinoma

Multilevel Whole-Genome Analysis Reveals Candidate Biomarkers in Clear Cell Renal Cell Carcinoma

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Post-transcriptional Regulation of MMP16 and TIMP2 Expression via miR-382, miR-410 and miR-200b in Endometrial Cancer

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