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      Up-Regulation of Angiotensin-Converting Enzyme ( ACE) Enhances Cell Proliferation and Predicts Poor Prognosis in Laryngeal Cancer

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          Abstract

          Background

          The angiotensin-converting enzyme (ACE, CD143) gene plays a crucial role in the pathology of many cancers. Previous studies mostly focused on the gene polymorphism, but the other functions of ACE have rarely been reported. The purpose of this study was to investigate the expression of ACE and its biological function, as well as its prognostic value, in laryngeal cancer.

          Material/Methods

          The expression of ACE was detected by quantitative real-time polymerase chain reaction (qRT-PCR) analysis in 106 patients with laryngeal cancer and 85 healthy people. Then the cell proliferation was estimated after the cell lines Hep-2 were transfected with pGL3-ACE and empty vector, respectively. In addition, the relationship between ACE expression and clinicopathologic characteristics was analyzed. Finally, Kaplan-Meier analysis was used to evaluate the overall survival of patients with different ACE expression, while Cox regression analysis was conducted to reveal the prognostic value of ACE in laryngeal cancer.

          Results

          Our results demonstrate that ACE is over-expressed in laryngeal cancer and thus promotes cell proliferation. The up-regulation of ACE was significantly influenced by tumor stage and lymph node metastasis. Patients with high ACE expression had a shorter overall survival compared with those with low ACE expression according to Kaplan-Meier analysis. The ACE gene was also found to be an important factor in the prognosis of laryngeal cancer.

          Conclusions

          Our study shows that the ACE gene was up-regulated, which promoted the cell proliferation, and it could be an independent prognostic marker in laryngeal cancer.

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          Most cited references34

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          Combined detection of serum exosomal miR-21 and HOTAIR as diagnostic and prognostic biomarkers for laryngeal squamous cell carcinoma.

          Jingting Wang, Yandong Zhou, Jianguang Lu … (2014)
          Serum exosomes containing noncoding RNA (ncRNA) play an important role in both physiological and pathological conditions. However, biological function of exosomal ncRNA remains unclear. The aim of the study was to investigate the prognostic and diagnostic values of exosomal ncRNA by comparing the amounts of exosomal miR-21 and HOTAIR in serum of laryngeal squamous cell carcinoma (LSCC) patients with those of polyps of vocal cords, and by determinating whether combined detection of the two molecules could provide useful information in the diagnosis of LSCC. Exosomes were isolated from the serum samples of 52 LSCC patients and those of 49 patients with polyps of vocal cords. TEM and Western blot were applied for the confirmation of isolated exosomes by observing the ultra structure and testing CD63 marker protein, respectively. RT-PCR was performed to detect the expression of miR-21 and HOTAIR in the exosomes. The receiver-operating characteristic (ROC) curve was generated to examine the prognostic value of the two molecules. The expression of exosomal miR-21 and HOTAIR was significantly higher in patients with LSCC than those with vocal cord polyps. There were significant differences of serum exosomal miR-21 and HOTAIR expressions between the advanced T classifications (T3/T4) or clinical stages (III/IV) and the early stages. The patients with lymph node metastasis had higher serum exosomal miR-21 and HOTAIR expressions than those without. There were no differences between patient sex, tumor locations and differentiations. The area under the ROC curve of combined examination of exosomal HOTAIR and miR-21 for diagnosing LSCC was 87.6 %, which was significantly higher than 80.1 % of miR-21 (p = 0.0359) or 72.7 % of HOTAIR (p = 0.0012), showing 94.2 and 73.5 % of sensitivity and specificity, respectively, in differentiating the malignant from benign laryngeal disease. Serum exosomal miR-21 and HOTAIR were significantly correlated with clinical parameters of LSCC, and combined evaluation of their serum expressions may be a valuable biomarker to screen LSCC and might be a promising predicting tool for LSCC patient.
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            Incidence and survival trends of head and neck squamous cell carcinoma in the Netherlands between 1989 and 2011.

            Boudewijn Braakhuis, C. René Leemans, Otto Visser (2014)
            Incidence and survival trends of head and neck squamous cell carcinoma (HNSCC) are essential knowledge for guiding policy making and research.
            Article 0 comments Cited 74 times – based on 0 reviews     Review now
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              Sequence variation in the human angiotensin converting enzyme.

              Mark J. Rieder, Scott Taylor, Andrew Clark … (1999)
              Angiotensin converting enzyme (encoded by the gene DCP1, also known as ACE) catalyses the conversion of angiotensin I to the physiologically active peptide angiotensin II, which controls fluid-electrolyte balance and systemic blood pressure. Because of its key function in the renin-angiotensin system, many association studies have been performed with DCP1. Nearly all studies have associated the presence (insertion, I) or absence (deletion, D) of a 287-bp Alu repeat element in intron 16 with the levels of circulating enzyme or cardiovascular pathophysiologies. Many epidemiological studies suggest that the DCP1*D allele confers increased susceptibility to cardiovascular disease; however, other reports have found no such association or even a beneficial effect. We present here the complete genomic sequence of DCP1 from 11 individuals, representing the longest contiguous scan (24 kb) for sequence variation in human DNA. We identified 78 varying sites in 22 chromosomes that resolved into 13 distinct haplotypes. Of the variant sites, 17 were in absolute linkage disequilibrium with the commonly typed Alu insertion/deletion polymorphism, producing two distinct and distantly related clades. We also identified a major subdivision in the Alu deletion clade that enables further analysis of the traits associated with this gene. The diversity uncovered in DCP1 is comparable to that described for other regions in the human genome. The highly correlated structure in DCP1 raises important issues for the determination of functional DNA variants within genes and genetic studies in humans based on marker association.
              Article 0 comments Cited 54 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Med Sci Monit
                Journal ID (iso-abbrev): Med. Sci. Monit
                Journal ID (publisher-id): Medical Science Monitor
                Title: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
                Publisher: International Scientific Literature, Inc.
                ISSN (Print): 1234-1010
                ISSN (Electronic): 1643-3750
                Publication date Collection: 2016
                Publication date (Electronic): 01 November 2016
                Volume: 22
                Pages: 4132-4138
                Affiliations
                Department of Otolaryngology, Liaocheng People’s Hospital and EENT Hospital, Liaocheng, Shandong, P.R. China
                Author notes
                Corresponding Author: Wen-sheng Ge, e-mail: wenshengyuner@ 123456sina.com
                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                Article
                Publisher ID: 896933
                DOI: 10.12659/MSM.896933
                PMC ID: 5094469
                PubMed ID: 27801393
                SO-VID: c284a444-cd3e-4d49-8009-41ee747b50aa
                Copyright © © Med Sci Monit, 2016
                License:

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License

                History
                Date received : 01 December 2015
                Date accepted : 18 January 2016
                Categories
                Subject: Clinical Research

                Keywords: angiotensin-converting enzyme inhibitors,cell proliferation,prognosis
                Data availability:
                Keywords: angiotensin-converting enzyme inhibitors, cell proliferation, prognosis

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