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

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

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

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 of menopause Family history of EOC, FTC, breast cancer Personal history of breast cancer Infertility/not bearing children Endometriosis Lynch Syndrome BRCA1/2 mutation CA CANCER J CLIN 2011;61:183–203

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 found in young women

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

2622 proteins detected by proteomic analysis Total proteins identified Differentially expressed between IOSE-b1 and IOSE cells Total Up-regulated P <0.01 P <0.05 Down-regulated 2,484 319 44 122 197 122 PROTEINS UP IN IOSE-b1 197 PROTEINS DOWN IN IOSE-b1 IOSE-b1 IOSE All proteins 2-fold up/down proteins, P <0.05

197 PROTEINS DOWN IN IOSE-b1 Heatmap analysis 122 PROTEINS UP IN IOSE-b1 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-b1 Protein-RNA complex assembly (6) Interphase of mitotic cell cycle (6) G1/S transition of mitotic cell cycle (3) Translation Initiation (5) RNA splicing (12) Negative regulation of caspase activity (3) IOSE-b1 IOSE P < 0.05

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

Validation of selected proteins by immunohistochemistry staining (EOC, serous) Primary Adjacent Metastasis LN (+) PIWIL1 ++ - ++ + PIWIL2 +++ - +++ +++ PIWIL3 +++ - +++ + PIWIL4 +++ - +++ +++

Validation of selected protein by immunohistochemistry staining (B2M in EOC)

Biogenesis and function of miRNA

Role of miRNAs in OC tumorigenesis and chemoresistance

Summary Human EOC is the most lethal gynaecological malignancy 319 proteins are differentially expressed between BRCA1 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 miRNAs in the regulation of OC tumorigenesis and chemoresistance

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

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