Reduced expression of SOX7 in ovarian cancer: a novel tumor suppressor through the Wnt/β-catenin signaling pathway

Abstract

BackgroundProducts of the SOX gene family play important roles in the life process. One of the members, SOX7, is associated with the development of a variety of cancers as a tumor suppression factor, but its relevance with ovarian cancer was unclear. In this study, we investigated the involvement of SOX7 in the progression and prognosis of epithelial ovarian cancer (EOC) and the involved mechanisms.MethodsExpression profiles in two independent microarray data sets were analyzed for SOX7 between malignant and normal tissues. The expression levels of SOX7 in EOC, borderline ovarian tumors and normal ovarian tissues were measured by immunohistochemistry. We also measured levels of COX2 and cyclin-D1 to examine their possible involvement in the same signal transduction pathway as SOX7.ResultsThe expression of SOX7 was significantly reduced in ovarian cancer tissues compared with normal controls, strongly indicating that SOX7 might be a negative regulator in the Wnt/β-catenin pathway in ovarian cancer. By immunohistochemistry staining, the protein expression of SOX7 showed a consistent trend with that of the gene expression microarray analysis. By contrast, the protein expression level of COX2 and cyclin-D1 increased as the tumor malignancy progressed, suggesting that SOX7 may function through the Wnt/β-catenin signaling pathway as a tumor suppressor. In comparison between the protein expression levels of SOX7 with pathological features of the cancer, we found that SOX7 was down-regulated mainly in serous cystadenocarcinoma and advanced stages of the cancers.ConclusionsThe expression of SOX7 correlates with tumor progression as a tumor suppressor, possibly through the Wnt/β-catenin signaling pathway in ovarian cancers, suggesting that SOX7 may be a promising prognostic marker.Electronic supplementary materialThe online version of this article (doi:10.1186/s13048-014-0087-1) contains supplementary material, which is available to authorized users.

β-Catenin expression is regulated by an IRES-dependent mechanism and stimulated by paclitaxel in human ovarian cancer cells

“…It is hardly detectable at the early stage, largely due to the lack of specific symptoms and reliable screening [2], so, surgical resection and subsequent chemotherapy are still the major therapeutic strategies [3]. However, the efficacy of chemotherapy is limited by chemoresistance [4].…”

Sex-determining region Y box-containing genes: regulators and biomarkers in gynecological cancers

“…Low level of SOX7 together with increased cyclooxygenase-2 and cyclin-D1 were detected in tissues from patients with epithelial OC, especially in patients with advanced serous cystadenocarcinoma 10 . This suggested that SOX7 might regulate cell proliferation by influencing the Wnt/β-catenin signaling pathway.…”

“…Thus, there is an urgent need to find novel diagnostic biomarkers for detecting OC at a premalignant stage 33 . SOX genes are identified as such biomarkers that can contribute to early screening and the prediction of clinical features in patients with OC, and regulation of SOX gene expression could influence cell proliferation and treatment efficacy at the cellular level 9,10,16,18,31,34 . …”

“…Researchers identified SOX1 , SOX7 , and SOX11 as tumor suppressor genes, with low expression level in patient samples due to aberrant CpG island hyper-methylation or unclear mechanisms 17,18 . Low expression level of these genes in cancerous tissues or serum was detected more frequently in patients with more advanced stage, higher grade, more aggressive tumor behavior, and shorter recurrence-free survival (RFS), while higher level was associated with the opposite clinical features 10,17,18,35,40 . These results suggested that analyzing SOX gene expression might be a good biomarker for predicting the prognosis of patients.…”

“…Additionally, analysis of abnormal SOX genes expression in patient samples contributed to the detection of early GC lesions 14-16 . Expression level of SOX genes was also considered as biomarkers associated with clinical features in patients with GCs, including International Federation of Gynecology and Obstetrics (FIGO) stage, histopathologic grade, and disease-free survival (DFS), as well as treatment response 10,15,17-19 . Understanding the mechanisms whereby SOX genes regulate the progression of GCs is therefore valuable and may facilitate the development of novel diagnostic, therapeutic, and prognostic strategies which aimed at improving the prognosis of women with GCs.…”