Whole genome oligonucleotide-based array comparative genomic hybridization analysis identified fibroblast growth factor I as a prognostic marker for advanced-stage serous ovarian adenocarcinomas

被引：108

作者：

Birrer, Michael J.

Johnson, Michael E.

Hao, Ke

Wong, Kwong-Kwok

Park, Dong-Choon

Bell, Aaron

Welch, William R.

Berkowitz, Ross S.

Mok, Samuel C.

机构：

[1] Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Gynecol Oncol,Dept Obstet & Gynecol, Boston, MA 02115 USA

[2] NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA

[3] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[4] Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA

[5] Dana Farber Harvard Canc Ctr, Gillette Ctr Womens Canc, Boston, MA USA

[6] Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA

[7] Catholic Univ Korea, St Vincent Hosp, Dept Obstet & Gynecol, Suwon, South Korea

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2007年 / 25卷 / 16期

关键词：

D O I：

10.1200/JCO.2006.09.0795

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose To identify markers that can predict overall survival in patients with high-grade advanced stage serous adenocarcinomas. Patients and Methods Oligonucleotide array comparative genomic hybridization (aCGH) was performed on 42 microdissected high-grade serous ovarian tumor samples. aCGH segments were obtained and a prediction Cox model was built and validated by the standard leave one out analysis. Both DNA and mRNA copy numbers of selected genes located on the candidate aCGH segments were determined by quantitative polymerase chain reaction (qPCR) and quantitative reverse transcriptase PCR (qRT-PCR) analyses. The gene that showed the highest correlation was further validated on an independent set of specimens and was selected for further functional studies. Results Two chromosomal regions, 4p16.3 and 5q31-5q35.3, exhibited the strongest correlation with overall survival (P <.01). From the 5q31 region, fibroblast growth factor 1 (FGF-1) was selected for further validation study. FGF-1 mRNA copy number was significantly correlated with DNA copy number and protein expression levels (P =.021 and <.001), and both FGF-1 mRNA and protein levels were significantly associated with overall survival (P =.018 and.042). This association was validated for protein expression on an independent set of 81 samples, significant to P =.006. Further studies showed significant correlation between FGF-1 protein expression and CD31 + staining in the tumor stroma (P =.024). Finally, both cancer cells and endothelial cells treated with exogenous FGF-1 showed a significant increase in cell motility and survival. Conclusion Amplification of FGF-1 at 5q31 in ovarian cancer tissues, leads to increased angiogenesis, and autocrine stimulation of cancer cells, which may result in poorer overall survival in patents with high-grade advanced stage serous ovarian cancer.

引用

页码：2281 / 2287

页数：7

共 27 条

[1] Comparative genomic hybridization using oligonucleotide microarrays and total genomic DNA [J].

Barrett, MT ;

Scheffer, A ;

Ben-Dor, A ;

Sampas, N ;

Lipson, D ;

Kincaid, R ;

Tsang, P ;

Curry, B ;

Baird, K ;

Meltzer, PS ;

Yakhini, Z ;

Bruhn, L ;

Laderman, S .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (51) :17765-17770

[2] TUMOR INTERACTIONS WITH THE VASCULATURE - ANGIOGENESIS AND TUMOR-METASTASIS [J].

BLOOD, CH ;

ZETTER, BR .

BIOCHIMICA ET BIOPHYSICA ACTA, 1990, 1032 (01) :89-118

[3] Expression profiling of serous low malignant potential, low-grade, and high-grade tumors of the ovary. [J].

Bonome, T ;

Lee, JY ;

Park, DC ;

Radonovich, M ;

Pise-Masison, C ;

Brady, J ;

Gardner, GJ ;

Hao, K ;

Wong, WH ;

Barrett, JC ;

Lu, KH ;

Sood, AK ;

Gershenson, DM ;

Mok, SC ;

Birrer, MJ .

CANCER RESEARCH, 2005, 65 (22) :10602-10612

[4]

Bourdon V, 2002, CANCER RES, V62, P6218

[5] High-resolution global profiling of genomic alterations with long oligonucleotide microarray [J].

Brennan, C ;

Zhang, YY ;

Leo, C ;

Feng, B ;

Cauwels, C ;

Aguirre, AJ ;

Kim, MJ ;

Protopopov, A ;

Chin, L .

CANCER RESEARCH, 2004, 64 (14) :4744-4748

[6]

Buffart TE, 2005, CELL ONCOL, V27, P57

[7] Microvessel density as a prognostic marker in bladder carcinoma: correlation with tumor grade, stage and prognosis. [J].

Canoglu A. ;

Gögüş C. ;

Bedük Y. ;

Orhan D. ;

Tulunay O. ;

Baltaci S. .

International Urology and Nephrology, 2004, 36 (3) :401-405

[8] Angiogenesis in the bone marrow of patients with breast cancer [J].

Chavez-MacGregor, M ;

Aviles-Salas, A ;

Green, D ;

Fuentes-Alburo, A ;

Gómez-Ruiz, C ;

Aguayo, A .

CLINICAL CANCER RESEARCH, 2005, 11 (15) :5396-5400

[9] Contact resistance measurement of bonded copper interconnects for three-dimensional integration technology [J].

Chen, KN ;

Fan, A ;

Tan, CS ;

Reif, R .

IEEE ELECTRON DEVICE LETTERS, 2004, 25 (01) :10-12

[10]

D'Amore P A, 1992, Semin Cancer Biol, V3, P49

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