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      SERPINB3 in the Chicken Model of Ovarian Cancer: A Prognostic Factor for Platinum Resistance and Survival in Patients with Epithelial Ovarian Cancer

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          Abstract

          Serine protease inhibitors (SERPINs) appear to be ubiquitously expressed in a variety of species and play important roles in pivotal physiological processes such as angiogenesis, immune responses, blood coagulation and fibronolysis. Of these, squamous cell carcinoma antigen 1 (SCCA1), also known as a SERPINB3, was first identified in squamous cell carcinoma tissue from the cervix of women. However, there is little known about the SERPINB3 expression in human epithelial ovarian cancer (EOC). Therefore, in the present study, we investigated the functional role of SERPINB3 gene in human EOC using chickens, the most relevant animal model. In 136 chickens, EOC was found in 10 (7.4%). SERPINB3 mRNA was induced in cancerous, but not normal ovaries of chickens (P<0.01), and it was abundant only in the glandular epithelium of cancerous ovaries of chickens. Further, several microRNAs, specifically miR-101, miR-1668 and miR-1681 were discovered to influence SERPINB3 expression via its 3′-UTR which suggests that post-transcriptional regulation influences SERPINB3 expression in chickens. SERPINB3 protein was localized predominantly to the glandular epithelium in cancerous ovaries of chickens, and it was abundant in the nucleus of both chicken and human ovarian cancer cell lines. In 109 human patients with EOC, 15 (13.8%), 66 (60.6%) and 28 (25.7%) patients showed weak, moderate and strong expression of SERPINB3 protein, respectively. Strong expression of SERPINB3 protein was a prognostic factor for platinum resistance (adjusted OR; odds ratio, 5.94; 95% Confidence Limits, 1.21–29.15), and for poor progression-free survival (PFS; adjusted HR; hazard ratio, 2.07; 95% CI; confidence interval, 1.03–4.41). Therefore, SERPINB3 may play an important role in ovarian carcinogenesis and be a novel biomarker for predicting platinum resistance and a poor prognosis for survival in patients with EOC.

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          Most cited references 37

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          Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.

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          The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-Delta Delta C(T)) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-Delta Delta C(T)) method. In addition, we present the derivation and applications of two variations of the 2(-Delta Delta C(T)) method that may be useful in the analysis of real-time, quantitative PCR data. Copyright 2001 Elsevier Science (USA).
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            MicroRNAs (miRNAs) are endogenous approximately 22 nt RNAs that can play important regulatory roles in animals and plants by targeting mRNAs for cleavage or translational repression. Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
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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
                2012
                21 November 2012
                : 7
                : 11
                Affiliations
                [1 ]WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Gwanak-gu, Seoul, Korea
                [2 ]Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Jongno-Gu, Seoul, Korea
                [3 ]Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Bundang-Gu, Seoungnam, Korea
                [4 ]Department of Pathology, Seoul National University College of Medicine, Jongno-Gu, Seoul, Korea
                [5 ]Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
                [6 ]Center for Animal Biotechnology and Genomics and Department of Animal Science, Texas A&M University, College Station, Texas, United States of America
                Beckman Research Institute of City of Hope, United States of America
                Author notes

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

                Conceived and designed the experiments: JYH YSS GS. Performed the experiments: WL HSK WJ SEA JK YBK MAK MKK HHC. Analyzed the data: JYH YSS FWB GS. Contributed reagents/materials/analysis tools: JYH YSS FWB GS. Wrote the paper: WL HSK FWB GS.

                Article
                PONE-D-12-12109
                10.1371/journal.pone.0049869
                3503859
                23185467

                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.

                Page count
                Pages: 10
                Funding
                This research was funded by the World Class University (WCU) program (R31-10056) and by Basic Science Research Program (2010-0013078) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology, and also by a grant from the Next-Generation BioGreen 21 Program (No. PJ008142), Rural Development Administration, Republic of Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Anatomy and Physiology
                Reproductive System
                Reproductive Physiology
                Medicine
                Diagnostic Medicine
                Pathology
                General Pathology
                Biomarkers
                Oncology
                Cancer Detection and Diagnosis
                Early Detection
                Cancers and Neoplasms
                Gynecological Tumors
                Ovarian Cancer
                Veterinary Science
                Animal Types
                Laboratory Animals
                Veterinary Anatomy and Physiology
                Veterinary Medicine
                Veterinary Oncology

                Uncategorized

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