Progression markers of human epithelialtype ovarian tumors Guoxiong

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Progression markers of human epithelial-type ovarian tumors Guoxiong Xu Jinshan Hospital, Fudan University Shanghai,

Progression markers of human epithelial-type ovarian tumors Guoxiong Xu Jinshan Hospital, Fudan University Shanghai, China 7 th International Conference and Expo on Molecular & Cancer Biomarkers September 16, 2016

Estimated Incidence and Mortality Worldwide Estimated number of cancer cases Both sexes (total 14,

Estimated Incidence and Mortality Worldwide Estimated number of cancer cases Both sexes (total 14, 067, 894) Estimated number of cancer deaths (total 8, 201, 575) Male (total 7, 410, 376) (total 4, 653, 385) Female (total 6, 657, 518) (total 3, 548, 190) #7 #8 Source: GLOBOCAN 2012

Estimated New Cancer Cases and Deaths Worldwide by Sex and Level of Economic Development

Estimated New Cancer Cases and Deaths Worldwide by Sex and Level of Economic Development Developed Countries Worldwide #5 #7 #8 #6 Developing Countries #8 Source: GLOBOCAN 2012 #8 3

Estimated global number of new cases and deaths with proportions by major world regions,

Estimated global number of new cases and deaths with proportions by major world regions, for ovarian cancer, 2012

Risk Factors for the Development of Ovarian Cancer • Age, especially around the time

Risk Factors for the Development of Ovarian Cancer • Age, especially around the time of menopause • Family history of EOC, FTC, breast cancer • Personal history of breast cancer • Infertility/not bearing children • Endometriosis • Lynch Syndrome • BRCA 1/2 mutation CA CANCER J CLIN 2011; 61: 183– 203

Types of Ovarian Cancer Surface epithelial ovarian cancer (EOC) Most common, about 95% of

Types of Ovarian Cancer Surface epithelial ovarian cancer (EOC) Most common, about 95% of ovarian cancer Sex cord-stromal cell cancer Uncommon Germ cell cancer Uncommon, usually women found in young

Characteristics of the main types of EOC 70% <5% 3% 10%

Characteristics of the main types of EOC 70% <5% 3% 10%

2622 proteins detected by proteomic analysis 2, 484 Differentially expressed between IOSE-b 1 and

2622 proteins detected by proteomic analysis 2, 484 Differentially expressed between IOSE-b 1 and IOSE cells Total Up-regulated P <0. 01 Up-regulated P <0. 05 Down-regulated P <0. 01 Down-regulated P <0. 05 319 44 122 44 197 All proteins 2 -fold up/down proteins, P <0. 05 IOSE-b 1 Total proteins identified 122 PROTEINS UP IN IOSE-b 1 197 PROTEINS DOWN IN IOSE-b 1 IOSE

Heatmap analysis 122 PROTEINS UP IN IOSE-b 1 Selected significant GO-Terms (GOFFA) (P <

Heatmap analysis 122 PROTEINS UP IN IOSE-b 1 Selected significant GO-Terms (GOFFA) (P < 0. 01, E 2. 0) Immune response (27) Cell proliferation (24) Cell motility (14) Programmed cell death (31) Regulation of apoptosis (23) Caspase activation (3) DNA damage response (3) 197 PROTEINS DOWN IN IOSE-b 1 P < 0. 05 IOSE Selected significant GO-Terms (GOFFA) (P < 0. 01, E 2. 0) Protein-RNA complex assembly (6) Interphase of mitotic cell cycle (6) G 1/S transition of mitotic cell cycle (3) Translation Initiation (5) RNA splicing (12) Negative regulation of caspase activity (3)

Validation of selected protein by immunohistochemistry staining (CSTB in EOC)

Validation of selected protein by immunohistochemistry staining (CSTB in EOC)

Adjacent Metastasis PIWIL 1 ++ - ++ + PIWIL 2 +++ - +++ PIWIL

Adjacent Metastasis PIWIL 1 ++ - ++ + PIWIL 2 +++ - +++ PIWIL 3 +++ - +++ + PIWIL 4 Validation of selected proteins by immunohistochemistry staining (EOC, serous) Primary LN (+) +++ - +++

Validation of selected protein by immunohistochemistry staining (B 2 M in EOC)

Validation of selected protein by immunohistochemistry staining (B 2 M in EOC)

Biogenesis and function of mi. RNA

Biogenesis and function of mi. RNA

Role of mi. RNAs in OC tumorigenesis and chemoresistance

Role of mi. RNAs in OC tumorigenesis and chemoresistance

Summary • Human EOC is the most lethal gynaecological malignancy • 319 proteins are

Summary • Human EOC is the most lethal gynaecological malignancy • 319 proteins are differentially expressed between BRCA 1 mutated and non-mutated cells • Using tissue microarray and immunohistochemistry, several potential ovarian tumor progression markers are identified • There is substantial evidence supporting a role of mi. RNAs in the regulation of OC tumorigenesis and chemoresistance

Acknowledgements Jinshan Hospital, Fudan University Lingyun Zhang Wenwen Sun Daibing Zhou Qunbo Lin Weimin

Acknowledgements Jinshan Hospital, Fudan University Lingyun Zhang Wenwen Sun Daibing Zhou Qunbo Lin Weimin Ren Xiaoling Tian Xingxing Wang Department of Gynecology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine Jianhua Liu Chao Chen Grants from the National Natural Science Foundation of China, Shanghai Committee of Science and Technology, Shanghai Municipal Health Bureau

Thank You

Thank You