Gene expression signatures of primary and metastatic uterine leiomyosarcoma.
Leiomyosarcoma (LMS) is the most common uterine sarcoma. Although the disease is relatively rare, it is responsible for considerable mortality due to frequent metastasis and chemoresistance. The molecular events related to LMS metastasis are unknown to date. The present study compared the global gene expression patterns of primary uterine LMSs and LMS metastases. Gene expression profiles of 13 primary and 15 metastatic uterine LMSs were analyzed using the HumanRef-8 BeadChip from Illumina. Differentially expressed candidate genes were validated using quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry. To identify differently expressed genes between primary and metastatic tumors, we performed one-way analysis of variance with Benjamini-Hochberg correction. This led to identification of 203 unique probes that were significantly differentially expressed in the 2 tumor groups by greater than 1.58-fold with P < .01, of which 94 and 109 were overexpressed in primary and metastatic LMSs, respectively. Genes overexpressed in primary uterine LMSs included OSTN, NLGN4X, NLGN1, SLITRK4, MASP1, XRN2, ASS1, RORB, HRASLS, and TSPAN7. Genes overexpressed in LMS metastases included TNNT1, FOLR3, TDO2, CRYM, GJA1, TSPAN10, THBS1, SGK1, SHMT1, EGR2, and AGT. Quantitative real-time PCR confirmed significant anatomical site-related differences in FOLR3, OSTN, and NLGN4X levels; and immunohistochemistry showed significant differences in TDO2 expression. Gene expression profiling differentiates primary uterine LMSs from LMS metastases. The molecular signatures unique to primary and metastatic LMSs may aid in understanding tumor progression in this cancer and in providing a molecular basis for prognostic studies and therapeutic target discovery.
Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, N-0424 Oslo, Norway; The Medical Faculty, University of Oslo, N-0316 Oslo, Norway. Electronic address: bend@medisin.uio.no.
Ben
B
Davidson
Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, N-0424 Oslo, Norway.
Vera Maria
VM
Abeler
Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, N-0424 Oslo, Norway.
Mette
M
Førsund
Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, N-0424 Oslo, Norway.
Arild
A
Holth
Genomic Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Yanqin
Y
Yang
Departments of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA; Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
Yusuke
Y
Kobayashi
Departments of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA; Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
Lily
L
Chen
Department of Gynecologic Oncology, Norwegian Radium Hospital, Oslo University Hospital, N-0424 Oslo, Norway; Institute for Medical Informatics, Norwegian Radium Hospital, Oslo University Hospital, N-0424 Oslo, Norway.
Gunnar B
GB
Kristensen
Departments of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA; Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
Ie-Ming
IeM
Shih
Departments of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA; Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA. Electronic address: tlw@welch.jhu.edu.
Tian-Li
TL
Wang
D016000:Cluster Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007890:Leiomyosarcoma / Q000235:genetics* / Q000556:secondary; D009362:Neoplasm Metastasis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome; D014594:Uterine Neoplasms / Q000235:genetics* / Q000473:pathology; D000090803:mu-Crystallins
Gene expression array; Metastasis; Uterine leiomyosarcoma