Expression Profiles of Genes Involved in Poor Prognosis of Epithelial Ovarian Carcinoma

Yoshida, Shozo; Furukawa, Naoto; Shoji, Hirokazu; Tanase, Yasuhito; Kanayama, Seiji; Noguchi, Taketoshi; Sakata, Mariko; Yamada, Yoshihiko; Oi, Hidekazu; Kobayashi, Hiroshi

doi:10.1111/igc.0b013e3181aaa93a

Cited by 53 publications

(52 citation statements)

References 33 publications

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“…The genetic basis of epithelial ovarian carcinomas is too complex to be reviewed in detail here, but numerous excellent reviews exist on this subject [60][61][62]. Recently, lncRNAs, as well as epithelial ovarian cancer disease progression and the prognosis of patients, have attracted great interest.…”

Section: Tumorigenesismentioning

confidence: 99%

Mechanism for the Decision of Ovarian Surface Epithelial Stem Cells to Undergo Neo-Oogenesis or Ovarian Tumorigenesis

Zheng

Hong

et al. 2018

Cell Physiol Biochem

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The ovary is surrounded by a whitish layer of mesodermally derived ovarian surface epithelium (OSE) that lines the intraembryonic celom and comprises simple squamous to cuboidal to low pseudostratified columnar epithelial cells. Its integrity is maintained by simple desmosomes, incomplete tight junctions, several integrins and cadherins. Recent research has found that ovarian stem cells (OSCs) exist within the OSE and may be responsible for both neo-oogenesis and ovarian cancer during adult life. The factors determining whether OSCs undergo neo-oogenesis or ovarian cancer are of great interest to researchers and clinicians. Accumulating evidence suggests the mechanism for the decision of ovarian surface epithelial stem cells to undergo either neo-oogenesis or ovarian cancer transformation may comprise both internal and external factors. Here, we review recent progress on how the internal factors, including genes, signaling pathways and lncRNA: OSE stem cells mediate the development and progression of ovarian cancer through various genes such as p53, KRAS, BRAF, and PTEN, and mutations in PIK3CA, and through various signaling pathways, including TGF-B pathway, Wnt signaling pathway, Notch signaling pathway, NF-kB signal transducer and transcriptional activator 3 (STAT3) pathway and Hedghog (HH) pathway. A series of expressions of IncRNA have changed in epithelial ovarian cancer tissues and cell lines compared to normal ovarian tissues and cell lines. As well as external factors, including incessant ovulation, gonadotropin and chronicinflammation: Frequent ovulation, without long-term dormancy, increases the risk of illness, because repeated rupture and repair at the ovulation site provides an opportunity for the accumulation of genetic aberrations; FSH affects all aspects of ovarian cancer metastasis, such as inhibition of apoptosis, through Induction of increased expression of VEGFA (VEGF) to support tumor growth, promote vascular growth, and possibly alter certain oncogenic pathways, thereby promoting proliferation and invasive phenotypic inflammation contributes to tumorigenesis, which help determine whether OSCs undergo neo-oogenesis or ovarian tumorigenesis. Understanding this issue is critical for developing novel strategies for premature ovarian failure and ovarian cancer prevention and therapy.

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Section: Tumorigenesismentioning

confidence: 99%

Mechanism for the Decision of Ovarian Surface Epithelial Stem Cells to Undergo Neo-Oogenesis or Ovarian Tumorigenesis

Zheng

Hong

et al. 2018

Cell Physiol Biochem

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“…A frequent alteration observed in poorly differentiated carcinomas in any tissue involves a reduction in E-cadherin expression, a master regulator of cell adhesion and polarity encoded by the CDH1 gene. [6][7][8] Dampening E-cadherin expression can occur in several ways, transcriptional repression being one of the most important. Known repressors of E-cadherin include zinc-finger transcription factors (Snail1 (SNAI1), Slug/Snail2 (SNAI2), ZEB2 (SIP1), and ZEB1 (d-EF1)), and basic helix-loop-helix transcription factors (E47 (TCF3), E2-2 (TCF4), or Twist).…”

mentioning

confidence: 99%

ZEB1 overexpression associated with E-cadherin and microRNA-200 downregulation is characteristic of undifferentiated endometrial carcinoma

et al. 2013

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Undifferentiated endometrial carcinomas are very aggressive high-grade endometrial carcinomas that are frequently under-recognized. This study aimed to analyze the molecular alterations underlying the development of these endometrial carcinomas, focusing on those related to dedifferentiation. We assessed a series of 120 tumors: 57 grade 1 and 2 endometrioid endometrial carcinomas, 15 grade 3 endometrioid endometrial carcinomas, 27 endometrial serous carcinomas, and 21 undifferentiated endometrial carcinomas. We found a high frequency of DNA mismatch repair deficiency (38%) and moderate rate of p53 overexpression (B33%) in undifferentiated carcinomas. In contrast to the characteristic endometrioid phenotype, there was a dramatic downregulation of E-cadherin expression in the undifferentiated subtype. Quantitative methylation studies dismissed CDH1 promoter hypermethylation as the mechanism responsible for this change in gene expression, while immunohistochemistry revealed that the E-cadherin repressor ZEB1 was frequently overexpressed (62%) in undifferentiated endometrial carcinomas. This finding was accompanied by a sharp downregulation in the expression of the miR-200 family of microRNAs, well-known targets of ZEB1. Furthermore, there was enhanced expression of epithelialto-mesenchymal transition markers in undifferentiated endometrial carcinomas, such as N-cadherin, cytoplasmic p120, and osteonectin. In addition, HMGA2, a regulator of epithelial-to-mesenchymal transition that is expressed in aggressive endometrial tumors, such as endometrial serous carcinomas and carcinosarcomas, was expressed in 420% of undifferentiated carcinomas. These results suggest that ZEB1 overexpression, associated with E-cadherin and miR-200s downregulation, and the expression of mesenchymal markers might enhance the metastatic potential of undifferentiated endometrial carcinomas, leading to a poor prognosis. In addition, our observations suggest that the immnohistochemical analysis of E-cadherin and ZEB1 can aid in the differential diagnosis of the more agressive undifferentiated endometrial carcinomas from grade 3 endometrioid carcinomas.

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“…Moreover, among 154 genes in aggressive ovarian cancers, 108 (70.1%) were associated with epithelial-mesenchymal transition (EMT)-related genes [82]. Further, detailed transcriptome analysis of chromosome 3 genes in serous epithelial ovarian cancers including EOC cell lines and malignant tumors revealed among 278 differentially expressed genes, three genes (RIS1, GBE1 and HEG1) that were similarly under-expressed in all the cancer samples studied [83], hower still without further detailed evidence in other investigations.…”

Section: Cd24mentioning

confidence: 99%

Ovarian cancer: Origin and factors involved in carcinogenesis with potential use in diagnosis, treatment and prognosis of the disease

Záveský

Jancárková²,

Kohoutová³

2011

neo

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Ovarian cancer representing the most lethal gynecologic malignancy escapes from the efforts to manage the disease. We reviewed the current state of the research considering three main concepts on origin of ovarian cancer including epithelialmesenchymal transition, secondary origin from Müllerian system and cancer stem cell hypothesis. Cytogenetic and molecular characteristics of ovarian cancer are focused particularly on microRNA expression studies revealing huge potential in recent years, although other transcriptomic, proteomic, epigenetic, epidemiologic and immunological factors are touched upon, too. Routine and investigated diagnostic and treatment methods are outlined and several factors revealed to be associated with prognosis of the disease. Despite the huge progress on elucidating factors involved in ovarian cancer carcinogenesis, still remains urgent need to improve both the diagnostics as well as the treatment.

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Expression Profiles of Genes Involved in Poor Prognosis of Epithelial Ovarian Carcinoma

Abstract: This review summarizes recent advances in prognosis-related molecular biology. Collectively, molecular changes possibly through EMT are considered to be a major contributor to the poor prognosis of EOC.

Cited by 53 publications

References 33 publications

Mechanism for the Decision of Ovarian Surface Epithelial Stem Cells to Undergo Neo-Oogenesis or Ovarian Tumorigenesis

Mechanism for the Decision of Ovarian Surface Epithelial Stem Cells to Undergo Neo-Oogenesis or Ovarian Tumorigenesis

ZEB1 overexpression associated with E-cadherin and microRNA-200 downregulation is characteristic of undifferentiated endometrial carcinoma

Ovarian cancer: Origin and factors involved in carcinogenesis with potential use in diagnosis, treatment and prognosis of the disease

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