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Tumor Progression Markers in Human Ovarian Tumors

Investigating epithelial-type ovarian tumors to identify progression markers, risk factors, and protein expression for potential treatment strategies and understanding ovarian cancer characteristics.

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Tumor Progression Markers in Human Ovarian Tumors

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  1. 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

  2. Estimated Incidence and Mortality Worldwide Estimated number of cancer cases Estimated number of cancer deaths Both sexes (total 14,067,894) (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

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

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

  5. 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

  6. 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

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

  8. 2622 proteins detected by proteomic analysis All proteins 2-fold up/down proteins, P <0.05 122 PROTEINS UP IN IOSE-b1 IOSE-b1 197 PROTEINS DOWN IN IOSE-b1 IOSE

  9. 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 Selected significant GO-Terms (GOFFA) (P < 0.01, E  2.0) 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

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

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

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

  13. Biogenesis and function of miRNA

  14. Role of miRNAs in OC tumorigenesis and chemoresistance

  15. 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

  16. 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

  17. Thank You

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