curatedOvarianData: clinically annotated data for the ovarian cancer transcriptome

Ganzfried, Benjamin Frederick; Riester, Markus; Haibe‐Kains, Benjamin; Risch, Thomas S.; Tyekucheva, Svitlana; Jazić, Ina; Wang, Xin Victoria; Ahmadifar, Mahnaz; Birrer, Michael J.; Parmigiani, Giovanni; Huttenhower, Curtis

doi:10.1093/database/bat013

Cited by 181 publications

(235 citation statements)

References 46 publications

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“…To determine the relationship between the expression of SLC6A12 and overall survival in patients with serous-type OC, we performed meta-analysis using curatedOvarianData, which includes more than 2000 expression profiles and clinical data from OC patients 10. The results of the meta-analysis showed that high expression of SLC6A12 was significantly associated with poor prognosis in serous-type OC patients (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The association between the expression level of SLC6A12 and prognosis in serous-type OC was validated using a recently developed meta-analysis package, curatedOvarianData,10 composed of 2066 expression profiles and clinical data of OC patients from 13 datasets including only serous OC. Cox proportional hazards model was used to determine hazard ratio (HR) for overall survival in each dataset, and univariate meta-analysis was performed using fixed effect model for combining HRs.…”

Section: Methodsmentioning

confidence: 99%

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Aberrant Hypomethylation ofSolute Carrier Family 6 Member 12Promoter Induces Metastasis of Ovarian Cancer

et al. 2017

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PurposeOvarian cancer (OC) is the most fatal of gynecological malignancies with a high rate of recurrence. We aimed to evaluate the expression of solute carrier family 6, member 12 (SLC6A12) and methylation of its promoter CpG sites in a xenograft mouse model of metastatic OC, and to investigate the regulatory mechanisms that promote aggressive properties during OC progression.Materials and MethodsExpression of SLC6A12 mRNA was determined by reverse-transcription quantitative polymerase chain reaction (RT-qPCR), and DNA methylation status of its promoter CpGs was detected by quantitative methylation-specific PCR. The metastatic potential of SLC6A12 was evaluated by in vitro migration/invasion transwell assays. Gene expression and DNA methylation of SLC6A12 and clinical outcomes were further investigated from publicly available databases from curatedOvarianData and The Cancer Genome Atlas.ResultsSLC6A12 expression was 8.1–14.0-fold upregulated and its DNA methylation of promoter CpG sites was 41–62% decreased in tumor metastases. After treatment with DNA methyltransferase inhibitor and/or histone deacetylase inhibitor, the expression of SLC6A12 was profoundly enhanced (~8.0-fold), strongly supporting DNA methylation-dependent epigenetic regulation of SLC6A12. Overexpression of SLC6A12 led to increased migration and invasion of ovarian carcinoma cells in vitro, approximately 2.0-fold and 3.3-fold, respectively. The meta-analysis showed that high expression of SLC6A12 was significantly associated with poor overall survival [hazard ratio (HR)=1.07, p value=0.016] and that low DNA methylation levels of SLC6A12 at specific promoter CpG site negatively affected patient survival.ConclusionOur findings provide novel evidence for the biological and clinical significance of SLC6A12 as a metastasis-promoting gene.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Aberrant Hypomethylation ofSolute Carrier Family 6 Member 12Promoter Induces Metastasis of Ovarian Cancer

et al. 2017

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“…NUAK1 transcript expression was assessed in a cohort of 1,262 patients assembled from seven publicly available, ovarian cancer Affymetrix microarray data sets downloaded from the curatedOvarianData database (14) and an independent cohort of 174 HGSOC patients with Agilent gene expression data (8) (Table 1). Of the ovarian cancer patients with Affymetrix data, 802 also had PFS data.…”

Section: Resultsmentioning

confidence: 99%

NUAK1 (ARK5) Is Associated with Poor Prognosis in Ovarian Cancer

et al. 2016

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Background and objectiveNua kinase 1 (NUAK1) was identified in multigene signatures of survival and suboptimal debulking in high-grade serous ovarian cancer (HGSOC). This study investigates the individual clinical and biologic contributions of NUAK1 in HGSOC patients and cell lines.MethodsPublic transcript expression, clinical, and outcome data were used to interrogate the relationship between NUAK1 and clinicopathologic factors and patient outcomes including progression-free survival (PFS) and molecular subtypes using logistic and Cox modeling. Analysis of NUAK1 transcript expression was performed in primary tumors from 34 HGSOC patients with < or ≥2 years PFS. The impact of silencing NUAK1 by RNA interference (RNAi) on the migratory potential and chemosensitivity of SOC cells was assessed in vitro.ResultsElevated NUAK1 transcript expression was associated with worse PFS (hazard ratio = 1.134), advanced stage (odds ratio, OR = 1.7), any residual disease (OR = 1.58), and mesenchymal disease subtype (OR = 7.79 ± 5.89). Elevated NUAK1 transcript expression was observed in HGSOC patients with < vs. ≥2 years PFS (p < 0.045). RNAi-mediated silencing of NUAK1 expression attenuated migration of OV90 and E3 HGSOC cells in vitro, but did not modulate sensitivity to cisplatin or paclitaxel.ConclusionElevated NUAK1 was associated with poor survival as well as advanced stage, residual disease after cytoreductive surgery and mesenchymal molecular subtype. NUAK1 impacted migration, but not chemosensitivity, in vitro. Additional studies are needed to further develop the concept of NUAK1 as a clinically deployable biomarker and therapeutic target in HGSOC.

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“…The Ovarian Tumor Tissue Consortium (OTTA) includes tissue-based studies and focuses on tumor biomarkers and survival [106,107], with several large efforts underway. Compilations of systematically harmonized public gene expression datasets such as curatedOvarianData [108] are complementary resources. Although these consortia and compendia represent large numbers of studies, analyses of the rarer histotypes, MC, LGSC, and CCC, remain underpowered.…”

Section: Challenges and Limitations In Studying Epidemiology Of Cancementioning

confidence: 99%

Challenges and Opportunities in Studying the Epidemiology of Ovarian Cancer Subtypes

et al. 2017

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Purpose of review Only recently has it become clear that epithelial ovarian cancer (EOC) is comprised of such distinct histotypes--with different cells of origin, morphology, molecular features, epidemiologic factors, clinical features, and survival patterns—that they can be thought of as different diseases sharing an anatomical location. Herein, we review opportunities and challenges in studying EOC heterogeneity, Recent findings The 2014 World Health Organization diagnostic guidelines incorporate accumulated evidence that high- and low-grade serous tumors have different underlying pathogenesis, and that, on the basis of shared molecular features, most high grade tumors, including some previously classified as endometrioid, are now considered to be high-grade serous. At the same time, several studies have reported that high-grade serous EOC, which is the most common histotype, is itself made up of reproducible subtypes discernable by gene expression patterns. Summary These major advances in understanding set the stage for a new era of research on EOC risk and clinical outcomes with the potential to reduce morbidity and mortality. We highlight the need for multidisciplinary studies with pathology review using the current guidelines, further molecular characterization of the histotypes and subtypes, inclusion of women of diverse racial/ethnic and socioeconomic backgrounds, and updated epidemiologic and clinical data relevant to current generations of women at risk of EOC.

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curatedOvarianData: clinically annotated data for the ovarian cancer transcriptome

Cited by 181 publications

References 46 publications

Aberrant Hypomethylation ofSolute Carrier Family 6 Member 12Promoter Induces Metastasis of Ovarian Cancer

Aberrant Hypomethylation ofSolute Carrier Family 6 Member 12Promoter Induces Metastasis of Ovarian Cancer

NUAK1 (ARK5) Is Associated with Poor Prognosis in Ovarian Cancer

Challenges and Opportunities in Studying the Epidemiology of Ovarian Cancer Subtypes

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