Jian Gao1,2, Liancheng Zhu1,2, Huiyu Zhuang3, Bei Lin4,5. 1. Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, 110004, Liaoning, China. 2. Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Benxi, Liaoning, China. 3. Department of Obstetrics and Gynecology, Beijing Chaoyang Hospital Affiliated To Capital Medical University, Beijing, 100043, China. 4. Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, 110004, Liaoning, China. prof_linbei@126.com. 5. Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Benxi, Liaoning, China. prof_linbei@126.com.
Abstract
INTRODUCTION: Ovarian cancer has a high mortality rate due to difficulties in early detection and chemotherapy resistance. Human epididymal protein 4 (HE4) has been adopted as a novel serum biomarker for early ovarian cancer diagnosis, and the presence of Lewis y antigen modifications on HE4 in ovarian cancer cell lines has been detected in previous studies. The aim of this study was to analyze the expression of HE4 and Lewis y antigen in human ovarian cancer in order to find a correlation between them, as well as with the clinical pathological parameters of patients with ovarian cancer. METHODS: Immunohistochemistry was used to detect the respective expression of these compounds in two patient groups (chemotherapy-resistant and chemotherapy-sensitive) containing a total of 95 patients. Then, a bioinformatic approach was adopted and online large sample databases (TCGA, CCLE, and GTEx; Metascape, Cytoscape) were used to explore the potential mechanisms of action of these compounds. RESULTS: The results of this study demonstrate that high HE4 and Lewis y expression could be used as markers for chemotherapy resistance and poor prognosis in patients with ovarian cancer. These two expression events were widely correlated in various cancer tissues and are thought to act by activating the p38 mitogen-activated protein kinases (MAPK) pathway and inducing Vascular Endothelial Growth Factor A (VEGFA), Prostaglandin-Endoperoxide Synthase 2 (PTGS2), Early Growth Response 1 (EGR1), and Hypoxia-Inducible Factor 1-Alpha (HIFI1A), thereby promoting malignant biological behavior and resistance in ovarian cancer. CONCLUSIONS: These findings not only reveal the possible mechanism by which HE4 and Lewis y antigen affect ovarian cancer but also identify a four-gene signature that could be very useful in ovarian cancer detection and/or the development of new targeted therapies.
INTRODUCTION: Ovarian cancer has a high mortality rate due to difficulties in early detection and chemotherapy resistance. Human epididymal protein 4 (HE4) has been adopted as a novel serum biomarker for early ovarian cancer diagnosis, and the presence of Lewis y antigen modifications on HE4 in ovarian cancer cell lines has been detected in previous studies. The aim of this study was to analyze the expression of HE4 and Lewis y antigen in human ovarian cancer in order to find a correlation between them, as well as with the clinical pathological parameters of patients with ovarian cancer. METHODS: Immunohistochemistry was used to detect the respective expression of these compounds in two patient groups (chemotherapy-resistant and chemotherapy-sensitive) containing a total of 95 patients. Then, a bioinformatic approach was adopted and online large sample databases (TCGA, CCLE, and GTEx; Metascape, Cytoscape) were used to explore the potential mechanisms of action of these compounds. RESULTS: The results of this study demonstrate that high HE4 and Lewis y expression could be used as markers for chemotherapy resistance and poor prognosis in patients with ovarian cancer. These two expression events were widely correlated in various cancer tissues and are thought to act by activating the p38 mitogen-activated protein kinases (MAPK) pathway and inducing Vascular Endothelial Growth Factor A (VEGFA), Prostaglandin-Endoperoxide Synthase 2 (PTGS2), Early Growth Response 1 (EGR1), and Hypoxia-Inducible Factor 1-Alpha (HIFI1A), thereby promoting malignant biological behavior and resistance in ovarian cancer. CONCLUSIONS: These findings not only reveal the possible mechanism by which HE4 and Lewis y antigen affect ovarian cancer but also identify a four-gene signature that could be very useful in ovarian cancer detection and/or the development of new targeted therapies.
Authors: Ronny Drapkin; Hans Henning von Horsten; Yafang Lin; Samuel C Mok; Christopher P Crum; William R Welch; Jonathan L Hecht Journal: Cancer Res Date: 2005-03-15 Impact factor: 12.701
Authors: K Kitamura; E Stockert; P Garin-Chesa; S Welt; K O Lloyd; K L Armour; T P Wallace; W J Harris; F J Carr; L J Old Journal: Proc Natl Acad Sci U S A Date: 1994-12-20 Impact factor: 11.205
Authors: Ingegerd Hellström; John Raycraft; Martha Hayden-Ledbetter; Jeffrey A Ledbetter; Michèl Schummer; Martin McIntosh; Charles Drescher; Nicole Urban; Karl Erik Hellström Journal: Cancer Res Date: 2003-07-01 Impact factor: 12.701