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      TFIIB-Related Factor 2 Over Expression Is a Prognosis Marker for Early-Stage Non-Small Cell Lung Cancer Correlated with Tumor Angiogenesis

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          Abstract

          Background

          The aim of this study was to examine BRF2 expression in patients with non-small cell lung cancer (NSCLC) and explore the relationship of BRF2 protein with clinicopathologic factors, tumor angiogenesis and prognosis.

          Methods

          Both BRF2 protein and intratumoral microvessels were examined by immunohistochemical staining in 107 non-small cell lung cancer patients. Intratumoral m icrovessel density (MVD) was measured by counting CD-34 positive immunostained endothelial cells. Western blot and RT-PCR analyses were utilized to investigate the BRF2 expression status in tissues

          Results

          A notably higher level of BRF2 expression was found in NSCLC tissues at protein levels. In addition, univariate and multivariate analysis demonstrated that BRF2 protein over-expression and high MVD were significantly associated with tumor relapse. Although BRF2 overexpression and high MVD indicated poor 5-year overall survival (p = 0.004 and p = 0.019, respectively), multivariate analysis demonstrated that only BRF2 overexpression was an independent prognostic factor for unfavorable overall survival (P = 0.021).

          Conclusions

          BRF2 is a promising biomarker to identify individuals with poor prognostic potential and a possible target for anti-angiogenic therapy for patients with early-stage NSCLC.

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          Most cited references19

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          Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles.

          DNA microarrays have been widely applied to cancer transcriptome analysis; however, the majority of such data are not easily accessible or comparable. Furthermore, several important analytic approaches have been applied to microarray analysis; however, their application is often limited. To overcome these limitations, we have developed Oncomine, a bioinformatics initiative aimed at collecting, standardizing, analyzing, and delivering cancer transcriptome data to the biomedical research community. Our analysis has identified the genes, pathways, and networks deregulated across 18,000 cancer gene expression microarrays, spanning the majority of cancer types and subtypes. Here, we provide an update on the initiative, describe the database and analysis modules, and highlight several notable observations. Results from this comprehensive analysis are available at http://www.oncomine.org.
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            Role of microRNAs in vascular diseases, inflammation, and angiogenesis.

            The integrity of the endothelial monolayer is fundamental for the homoeostasis of the vascular system. Functional endothelial cells are also required for the growth of new blood vessels during neovascularization. Although multiple growth factors have been shown to regulate angiogenesis and vascular development, little is known about the complex upstream regulation of gene expression and translation. MicroRNAs (miRNAs) are an emerging class of highly conserved, non-coding small RNAs that regulate gene expression on the post-transcriptional level by inhibiting the translation of protein from mRNA or by promoting the degradation of mRNA. More than 500 human miRNAs have been identified so far, and increasing evidence indicates that miRNAs have distinct expression profiles and play crucial roles in various physiological and pathological processes such as cardiogenesis, haematopoietic lineage differentiation, and oncogenesis. Meanwhile, a few specific miRNAs that regulate endothelial cell functions and angiogenesis have been described. Let7-f, miR-27b, and mir-130a were identified as pro-angiogenic miRNAs. In contrast, miR-221 and miR-222 inhibit endothelial cell migration, proliferation, and angiogenesis in vitro by targeting the stem cell factor receptor c-kit and indirectly regulating endothelial nitric oxide synthase expression. Moreover, some miRNAs are involved in tumour angiogenesis such as the miR-17-92 cluster and miR-378. Early studies also indicate the contribution of specific miRNAs (e.g. miR-155, miR-21, and miR-126) to vascular inflammation and diseases. Thus, the identification of miRNAs and their respective targets may offer new therapeutic strategies to treat vascular diseases such as atherosclerosis, to improve neovascularization after ischaemia, or to prevent tumour progression.
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              Recruitment of RNA polymerase III to its target promoters.

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                11 February 2014
                : 9
                : 2
                : e88032
                Affiliations
                [1]Department of Thoracic Surgery, Qilu Hospital, Shandong University, Jinan, P. R. China
                University of Texas MD Anderson Cancer Center, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: ML HT. Performed the experiments: ML WY LL SL LQ WH. Analyzed the data: ML HT CG LS SL. Contributed reagents/materials/analysis tools: ML HT. Wrote the paper: ML HT.

                Article
                PONE-D-13-34331
                10.1371/journal.pone.0088032
                3921153
                24523874
                9cf40f91-20f4-4b36-8ab1-065ac313cf34
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 22 August 2013
                : 2 January 2014
                Page count
                Pages: 7
                Funding
                Project supported by the National Natural Science Foundation of China (No. 30571844), and the Science and Technology Development Foundation of Shandong Province (No. 2009GG10002007), and the National Natural Science Foundation of Shandong Province (No. ZR2009CM090), and the Wu Jie Ping Foundation (No. 320.6750.12393). Sponsors had no involvement in the study design, in the collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. The funders had no role in study design, data collection and analysis.
                Categories
                Research Article
                Medicine
                Diagnostic Medicine
                Pathology
                General Pathology
                Biomarkers
                Oncology
                Basic Cancer Research
                Metastasis
                Cancers and Neoplasms
                Lung and Intrathoracic Tumors
                Non-Small Cell Lung Cancer
                Cancer Risk Factors
                Surgery

                Uncategorized
                Uncategorized

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