Genome-wide gene expression profiles of ovarian carcinoma: Identification of molecular targets for the treatment of ovarian carcinoma

Nikolova, Dragomira; Doganov, N; Dimitrov, Rumen; Angelov, Krasimir; Low, Siew‐Kee; Dimova, Ivanka; Тончева, Драга; Nakamura, Yusuke; Zembutsu, Hitoshi

doi:10.3892/mmr_00000109

Cited by 9 publications

(5 citation statements)

References 48 publications

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“…CHMP4C is involved in the final steps of cell division, co-ordinating midbody resolution with the abscission checkpoint 13 and its transcription is regulated by TP53 to enhance exosome production 14 . A more recently study has shown that CHMP4C is frequently overexpressed in ovarian tumor tissues, with the suggestion that it may represent a diagnostic tumor marker and therapeutic -target for patients with the disease 15 .…”

Section: Resultsmentioning

confidence: 99%

GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

Pharoah¹,

Tsai²,

Ramus³

et al. 2013

Nat Genet

340

380

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Genome wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC) with another two loci being close to genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the United Kingdom. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. Follow-up genotyping was carried out in 18,174 cases and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 previously near genome-wide significance and identified three novel loci associated with risk; two loci associated with all EOC subtypes, at 8q21 (rs11782652, P=5.5×10-9) and 10p12 (rs1243180; P=1.8×10-8), and another locus specific to the serous subtype at 17q12 (rs757210; P=8.1×10-10). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility that implicates CHMP4C in the pathogenesis of ovarian cancer.

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Section: Resultsmentioning

confidence: 99%

GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

Pharoah¹,

Tsai²,

Ramus³

et al. 2013

Nat Genet

340

380

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“…SLC16A14 belongs to the group of monocarboxylate transporters 38 . It is downregulated in ovarian tumors compared to normal tissues 39 , and it is related to drug resistance of ovarian cancer cells in vitro 11 . We did not corroborate the role of SLC16A14 in drug resistance of ovarian cancer; however, we found association of high SLC16A14 expression level with longer PFS.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling Reveals Novel Candidate Markers of Ovarian Carcinoma Intraperitoneal Metastasis

Elsnerová¹,

Bartáková²,

Tihlarik³

et al. 2017

J. Cancer

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Epithelial ovarian cancer (EOC) has the highest mortality among gynecological carcinomas. The lack of specific markers for prognostic determination of EOC progression hinders the search for novel effective therapies.The aim of the present study was (i) to explore differences in expressions of ATP-binding cassette (ABC) and solute carrier (SLC) transporter genes, genes associated with drug metabolism and cell cycle regulation between control ovarian tissues (n = 14), primary EOCs (n = 44) and intraperitoneal metastases (n = 29); (ii) to investigate associations of gene expression levels with prognosis of patients with intraperitoneal metastases.In all tissue samples, transcript levels of the above target genes were assessed using quantitative real-time PCR. Gene expression levels were compared between particular tissue types and evaluated with regard to progression-free survival (PFS) and drug-resistance status of patients with metastases.Gene expression of ABCA7 significantly increased and that of ESR2 decreased in the order control ovarian tissues - primary EOCs - metastases. High expressions of ABCA2/8/9/10, ABCB1, ABCC9, ABCG2, ATP7A, SLC16A14, and SOD3 genes were significantly associated with longer progression-free survival of patients. In intraperitoneal metastases, expression of all of these genes highly correlated and indicated prognostic profile. Transporters from the ABCA family, ABCG2, and ESR2 are involved mainly in lipid metabolism, membrane transport, and cell proliferation. These processes are thus probably the most important for EOC progression.Based on these results, we have proposed novel markers of ovarian carcinoma progression and metastatic spread which might be potentially useful as therapeutic targets. Their significance should be further explored on a larger independent set of patients.

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“…Its protein expression was mostly reduced in various pancreatic ductal adenocarcinomas compared with normal ducts (Li et al, 2008). Another ESCRT-III subunit, Chmp4C, was frequently overexpressed in ovarian carcinoma tissue, and not expressed in control tissues (Nikolova et al, 2009). Genome wide association studies identified Chmp4C as a candidate susceptibility gene contributing to an excess familial risk to epithelial ovarian cancers (EOC) and found it to be overexpressed in two epithelial ovarian cancer cell lines and in primary EOC tissues (Pharoah et al, 2013).…”

Section: Tumor Samplesmentioning

confidence: 99%

The role of the endosomal sorting complexes required for transport (ESCRT) in tumorigenesis

Mattissek

Teis

2014

Molecular Membrane Biology

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The endosomal sorting complexes required for transport (ESCRT) are needed for three distinct cellular functions in higher eukaryotes: (i) Multivesicular body formation for the degradation of transmembrane proteins in lysosomes, (ii) midbody abscission during cytokinesis and (iii) retroviral budding. Not surprisingly, loss of ESCRT function has severe consequences, which include the failure to down-regulate growth factor receptors leading to deregulated mitogenic signaling. While it is clear that the function of the ESCRT machinery is important for embryonic development, its role in cancer is more controversial. Various experimental approaches in different model organisms arrive at partially divergent conclusions regarding the contribution of ESCRTs to tumorigenesis. Therefore the aim of this review is to provide an overview on different model systems used to study the role of the ESCRT machinery in cancer development, to highlight common grounds and present certain controversies in the field.

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Genome-wide gene expression profiles of ovarian carcinoma: Identification of molecular targets for the treatment of ovarian carcinoma

Cited by 9 publications

References 48 publications

GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

Gene Expression Profiling Reveals Novel Candidate Markers of Ovarian Carcinoma Intraperitoneal Metastasis

The role of the endosomal sorting complexes required for transport (ESCRT) in tumorigenesis

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