Gene expression data reveal common pathways that characterize the unifocal nature of ovarian cancer.
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.


METHODS
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 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 = .006), colon cancer (1 pathway at P = .005), and leukemia (P = .05). Artesunate-induced TGF-WNT pathway inhibition impaired OVCA cell migration.


CONCLUSIONS
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.
Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Experimental Therapeutics Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
Douglas C
DC
Marchion
Yin
Y
Xiong
Hye Sook
HS
Chon
Entidhar
E
Al Sawah
Nadim
N
Bou Zgheib
Ingrid J
IJ
Ramirez
Forough
F
Abbasi
Xiaomang B
XB
Stickles
Patricia L
PL
Judson
Ardeshir
A
Hakam
Jesus
J
Gonzalez-Bosquet
Robert M
RM
Wenham
Sachin M
SM
Apte
Anders E
AE
Berglund
Johnathan M
JM
Lancaster
D000328:Adult; D055088:Early Detection of Cancer; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D016158:Genes, p53; D006801:Humans; D009154:Mutation; D009362:Neoplasm Metastasis / Q000235:genetics / Q000503:physiopathology; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D025341:Principal Component Analysis; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology; D016019:Survival Analysis; D046888:Tissue Array Analysis
gene expression; p53 mutation; serous ovarian cancer; unifocal