- 作者：Douglas C. Marchion ; Yin Xiong ; Hye Sook Chon ; Entidhar Al Sawah ; Nadim Bou Zgheib ; Ingrid J. Ramirez ; Forough Abbasi ; Xiaomang B. Stickles ; Patricia L. Judson ; Ardeshir Hakam ; Jesus Gonzalez-Bosquet ; Robert M. Wenham ; Sachin M. Apte ; Anders E. Berglund ; Johnathan M. Lancaster
- 关键词：gene expression ; p53 mutation ; serous ovarian cancer ; unifocal
- 刊名：American Journal of Obstetrics and Gynecology
- 出版年：December, 2013
- 年：2013
- 卷：209
- 期：6
- 页码：576.e1-576.e16
- 全文大小：2775 K
Objective
The objective of the study was to evaluate the biological validity of ovarian cancer (OVCA) screening and early detection efforts and to characterize signaling pathways associated with human cancer metastasis and patient survival.Study Design
Using genome-wide expression profiling and deoxyribonucleic acid sequencing, we compared pelvic and matched extrapelvic implants from 30 patients with advanced-stage OVCA for expression of molecular signaling pathways and p53 gene mutations. Differentially expressed pathways were further evaluated in a series of primary or early-stage vs metastatic or recurrent cancer samples from 389 ovarian, prostate, and oral cancer patients. Metastasis pathways were also evaluated for associations with survival in 9 independent clinicogenomic datasets from 1691 ovarian, breast, colon, brain, and lung cancer and leukemia patients. The inhibitory effects of 1 pathway (transforming growth factor [TGF]-WNT) on in聽vitro OVCA cell migration were studied.
Results
Pelvic and extrapelvic OVCA implants demonstrated similar patterns of signaling pathway expression and identical p53 mutations. However, we identified 3 molecular pathways/cellular processes that were differentially expressed between pelvic and extrapelvic OVCA samples and between primary/early-stage and metastatic/advanced or recurrent ovarian, oral, and prostate cancers. Furthermore, their expression was associated with overall survival from ovarian cancer (P聽= .006), colon cancer (1 pathway at P聽= .005), and leukemia (P聽= .05). Artesunate-induced TGF-WNT pathway inhibition impaired OVCA cell migration.
Conclusion
Advanced-stage OVCA has a unifocal origin in the pelvis. Molecular pathways associated with extrapelvic OVCA spread are also associated with metastasis from other human cancers and with overall patient survival. Such pathways represent appealing therapeutic targets for patients with metastatic disease.