Evidence map›Paper›PMID 29951943›Full record

ArticleHormones & cancer2018

RNA Sequencing of Carboplatin- and Paclitaxel-Resistant Endometrial Cancer Cells Reveals New Stratification Markers and Molecular Targets for Cancer Treatment.

Raffaele Hellweg, Ashley Mooneyham, Zenas Chang, Mihir Shetty, Edith Emmings, Yoshie Iizuka, Christopher Clark, Timothy Starr, Juan H Abrahante, Florian Schütz and 3 more

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

Article in Hormones & cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.7field-weighted citation impact, top 30% 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

12 citing papers in PubMed, 21 citations in OpenAlex.

  1. LncRNANon-coding RNA research · 2025
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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

13 authors at 3 institutions in 2 countries.

Raffaele HellwegMasonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota Twin Cities, Room 490, 420 Delaware Street S.E., Minneapolis, MN, 55455, USA.
Ashley MooneyhamMasonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota Twin Cities, Room 490, 420 Delaware Street S.E., Minneapolis, MN, 55455, USA.
Zenas ChangDepartment of Women's Health, University of Minnesota, Minneapolis, MN, USA.
Mihir ShettyMasonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota Twin Cities, Room 490, 420 Delaware Street S.E., Minneapolis, MN, 55455, USA.
Edith EmmingsMasonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota Twin Cities, Room 490, 420 Delaware Street S.E., Minneapolis, MN, 55455, USA.
Yoshie IizukaMasonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota Twin Cities, Room 490, 420 Delaware Street S.E., Minneapolis, MN, 55455, USA.
Christopher ClarkMasonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota Twin Cities, Room 490, 420 Delaware Street S.E., Minneapolis, MN, 55455, USA.
Timothy StarrMasonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota Twin Cities, Room 490, 420 Delaware Street S.E., Minneapolis, MN, 55455, USA.
Juan H AbrahanteUniversity of Minnesota Informatics Institute, University of Minnesota, Minneapolis, MN, USA.
Florian SchützHeidelberg University Breast Unit, Heidelberg, Germany.
Gottfried KonecnyGynecologic Oncology, Hematology and Oncology Department, UCLA Medical Center, Santa Monica, CA, USA.
Peter ArgentaDepartment of Women's Health, University of Minnesota, Minneapolis, MN, USA.
Martina BazzaroMasonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota Twin Cities, Room 490, 420 Delaware Street S.E., Minneapolis, MN, 55455, USA. mbazzaro@umn.edu.
University of Minnesota · USHeidelberg University · DEUCLA Medical Center · US

Funding

TRAINING GRANT IN MICROBIOLOGY/CANCER RESEARCHT32CA009138 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Scott M. Dehm · 1985 to 2026
$11.3M
NCI NIH HHS T32 CA009138
6 · The paper itself

Abstract

Despite advances in surgical technique and adjuvant treatment, endometrial cancer has recently seen an increase in incidence and mortality in the USA. The majority of endometrial cancers can be cured by surgery alone or in combination with adjuvant chemo- or radiotherapy; however, a subset of patients experience recurrence for reasons that remain unclear. Recurrence is associated with chemoresistance to carboplatin and paclitaxel and consequentially, high mortality. Understanding the pathways involved in endometrial cancer chemoresistance is paramount for the identification of biomarkers and novel molecular targets for this disease. Here, we generated the first matched pairs of carboplatin-sensitive/carboplatin-resistant and paclitaxel-sensitive/paclitaxel-resistant endometrial cancer cells and subjected them to bulk RNA sequencing analysis. We found that 45 genes are commonly upregulated in carboplatin- and paclitaxel-resistant cells as compared to controls. Of these, the leukemia inhibitory factor, (LIF), the protein tyrosine phosphatase type IVA, member 3 (PTP4A3), and the transforming growth factor beta 1 (TGFB1) showed a highly significant correlation between expression level and endometrial cancer overall survival (OS) and can stratify the 545 endometrial cancer patients in the TCGA cohort into a high-risk and low-risk-cohorts. Additionally, four genes within the 45 upregulated chemoresistance-associated genes are ADAMTS5, MICAL2, STAT5A, and PTP4A3 codes for proteins for which small-molecule inhibitors already exist. We identified these proteins as molecular targets for chemoresistant endometrial cancer and showed that treatment with their correspondent inhibitors effectively killed otherwise chemoresistant cells. Collectively, these findings underline the utility of matched pair of chemosensitive and chemoresistant cancer cells to identify markers for endometrial cancer risk stratification and to serve as a pharmacogenomics model for identification of alternative chemotherapy approaches for treatment of patients with recurrent disease.

Indexed as

BiomarkersCarboplatinEndometrial NeoplasmsFemaleHumansPaclitaxelSequence Analysis, RNABiomarkersCarboplatinPaclitaxelChemoresistanceEndometrial cancerGene expressionRecurrence

Identifiers

PMID29951943
PMCPMC10355894
OpenAlexW2810076969

What OpenQuestion holds

Textmetadata
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.