Tubal Origin of "Ovarian" Low-Grade Serous Carcinoma: A Gene Expression Profile Study.

Yiying Wang,Shuhui Hong,Jayanthi Lea,Jingyi Mu,Beihua Kong,Yue Wang,Wenxin Zheng

doi:10.1155/2019/8659754

Abstract

Objective Ovarian low-grade serous carcinomas are thought to evolve in a stepwise fashion from ovarian epithelial inclusions, serous cystadenomas, and serous borderline tumors. Our previous study with clinicopathological approach showed that the majority ovarian epithelial inclusions are derived from the fallopian tubal epithelia rather than from ovarian surface epithelia. This study was designed to gain further insight into the cellular origin of ovarian low-grade serous carcinomas by differential gene expression profiling studies. Methods Gene expression profiles were studied in 43 samples including 11 ovarian low-grade serous carcinomas, 7 serous borderline tumors, 6 serous cystadenomas, 6 ovarian epithelial inclusions, 7 fallopian tubal epithelia, and 6 ovarian surface epithelia. Comprehensive analyses with hierarchical clustering, Rank-sum analysis and Pearson correlation tests were performed. Final validation was done on selected genes and corresponding proteins. Results The gene expression profiles distinguished ovarian low-grade serous carcinomas from ovarian surface epithelia, but not from fallopian tubal epithelia cells. Hierarchical clustering analysis showed ovarian serous tumors and ovarian epithelial inclusions were clustered closely in a branch, but separated from ovarian surface epithelia. The results were further validated by selected proteins of OVGP1, WT-1, and FOM3, which were highly expressed in the samples of the fallopian tube, ovarian epithelial inclusions, and ovarian serous tumors, but not in ovarian surface epithelia. The reverse was true for the protein expression patterns of ARX and FNC1. Conclusions This study provides evidence in a molecular level that ovarian low-grade serous carcinomas likely originate from the fallopian tube rather than from ovarian surface epithelia. Similar gene expression profiles among fallopian tube, ovarian epithelial inclusions, and serous tumors further support that ovarian low-grade serous carcinomas develop in a stepwise fashion. Such findings may have a significant implication for “ovarian” cancer-prevention strategies.

Highlights

Ovarian cancer is a leading cause of cancer deaths among women
Unsupervised hierarchical clustering of the individual low-grade serous carcinomas (LGSC) samples after robust multiarray average normalization showed that the samples of fallopian tube epithelia (FTE) and LGSC had closely related global gene expression profiles
No clustering association was found from the samples of LGSC, serous borderline tumor (SBT), serous cystadenoma, and OEI compared with the samples of ovarian surface epithelia (OSE) (Figure 1)

Summary

Introduction

Among all types of ovarian cancers, ovarian epithelial cancers (OEC), those with serous histology, are responsible for the majority of cancer related mortality [1]. Serous carcinomas of the ovary are divided into high-grade serous carcinomas (HGSC) and low-grade serous carcinomas (LGSC)[2]. This categorization arises from the difference seen with regard to epidemiological and genetic risk factors, precursor lesions, patterns of spreading, molecular events during oncogenesis, response to chemotherapy, and prognosis [3,4,5]. The cell of origin of ovarian serous cancers was thought to be derived from ovarian surface epithelia (OSE)[6, 7]

Methods

Results

Discussion

Conclusion