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
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

3. 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

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
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

9. 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

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

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

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

17. Biogenesis and function of miRNA

18. Role of miRNAs in OC tumorigenesis and chemoresistance

19. 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

20. 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

21. Thank You