Evidence map›Paper›PMID 34215221›Full record

ArticleBMC cancer2021

Differential gene expression identifies a transcriptional regulatory network involving ER-alpha and PITX1 in invasive epithelial ovarian cancer.

Yichao Li, Sushil K Jaiswal, Rupleen Kaur, Dana Alsaadi, Xiaoyu Liang, Frank Drews, Julie A DeLoia, Thomas Krivak, Hanna M Petrykowska, Valer Gotea and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.0field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Epigenetic Modulation of Estrogen Receptor Signaling in Ovarian Cancer.International journal of molecular sciences · 2024
    Review
  6. PITX1 plays essential functions in cancer.Frontiers in oncology · 2023
    Review
  7. Article
  8. Molecular Management of High-Grade Serous Ovarian Carcinoma.International journal of molecular sciences · 2022
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 1 country.

Yichao LiSchool of Electrical Engineering and Computer Science, Ohio University, Athens, OH, USA.
Sushil K JaiswalTranslational Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Rupleen KaurTranslational Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Dana AlsaadiTranslational Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Xiaoyu LiangSchool of Electrical Engineering and Computer Science, Ohio University, Athens, OH, USA.
Frank DrewsSchool of Electrical Engineering and Computer Science, Ohio University, Athens, OH, USA.
Julie A DeLoiaPresent address: Dignity Health Global Education, Roanoke, Virginia, USA.
Thomas KrivakDepartment of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh Medical School, Pittsburgh, PA, USA.
Hanna M PetrykowskaTranslational Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Valer GoteaTranslational Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Lonnie WelchSchool of Electrical Engineering and Computer Science, Ohio University, Athens, OH, USA.
Laura ElnitskiTranslational Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA. elnitski@mail.nih.gov.
National Institutes of Health · USOhio University · USNational Human Genome Research Institute · USDignity Health · USUniversity of Pittsburgh · US

Funding

Regulatory and epigenetic landscapes reveal biological processes, disease mechanisms and diagnostic markersZIAHG200323 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI ELNITSKI, LAURA L · 2009 to 2025
$27.6M
6 · The paper itself

Abstract

backgroundThe heterogeneous subtypes and stages of epithelial ovarian cancer (EOC) differ in their biological features, invasiveness, and response to chemotherapy, but the transcriptional regulators causing their differences remain nebulous.

methodsIn this study, we compared high-grade serous ovarian cancers (HGSOCs) to low malignant potential or serous borderline tumors (SBTs). Our aim was to discover new regulatory factors causing distinct biological properties of HGSOCs and SBTs.

resultsIn a discovery dataset, we identified 11 differentially expressed genes (DEGs) between SBTs and HGSOCs. Their expression correctly classified 95% of 267 validation samples. Two of the DEGs, TMEM30B and TSPAN1, were significantly associated with worse overall survival in patients with HGSOC. We also identified 17 DEGs that distinguished stage II vs. III HGSOC. In these two DEG promoter sets, we identified significant enrichment of predicted transcription factor binding sites, including those of RARA, FOXF1, BHLHE41, and PITX1. Using published ChIP-seq data acquired from multiple non-ovarian cell types, we showed additional regulatory factors, including AP2-gamma/TFAP2C, FOXA1, and BHLHE40, bound at the majority of DEG promoters. Several of the factors are known to cooperate with and predict the presence of nuclear hormone receptor estrogen receptor alpha (ER-alpha). We experimentally confirmed ER-alpha and PITX1 presence at the DEGs by performing ChIP-seq analysis using the ovarian cancer cell line PEO4. Finally, RNA-seq analysis identified recurrent gene fusion events in our EOC tumor set. Some of these fusions were significantly associated with survival in HGSOC patients; however, the fusion genes are not regulated by the transcription factors identified for the DEGs.

conclusionsThese data implicate an estrogen-responsive regulatory network in the differential gene expression between ovarian cancer subtypes and stages, which includes PITX1. Importantly, the transcription factors associated with our DEG promoters are known to form the MegaTrans complex in breast cancer. This is the first study to implicate the MegaTrans complex in contributing to the distinct biological trajectories of malignant and indolent ovarian cancer subtypes.

Indexed as

Carcinoma, Ovarian EpithelialEstrogen Receptor alphaFemaleGene Expression Regulation, NeoplasticGene Regulatory NetworksHumansPaired Box Transcription FactorsESR1 protein, humanEstrogen Receptor alphahomeobox protein PITX1Paired Box Transcription FactorsERαEstrogen receptor-alphaHGSOCHigh-grade serous ovarian cancerLGSOCLow-grade serous ovarian cancerMegaTrans complexPITX1SBTSerous borderline tumor

Identifiers

PMID34215221
PMCPMC8254236
OpenAlexW3174062038

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.