Evidence map›Paper›PMID 32295249›Full record

ArticleCancers2020

Aspartate-β-Hydroxylase: A Promising Target to Limit the Local Invasiveness of Colorectal Cancer.

Roberto Benelli, Delfina Costa, Luca Mastracci, Federica Grillo, Mark Jon Olsen, Paola Barboro, Alessandro Poggi, Nicoletta Ferrari

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
0.7field-weighted citation impact, top 36% 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

17 citing papers in PubMed, 20 citations in OpenAlex.

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  13. Characterization of the Relationship Between the Expression of Aspartate β-Hydroxylase and the Pathological Characteristics of Breast Cancer.Medical science monitor : international medical journal of experimental and clinical research · 2020
    Article
  14. Review
  15. Aspartate β-hydroxylase as a target for cancer therapy.Journal of experimental & clinical cancer research : CR · 2020
    Review
  16. Article
  17. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Roberto BenelliSSD Oncologia Molecolare e Angiogenesi, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genova, Italy.ORCID 0000-0002-9769-0954
Delfina CostaSSD Oncologia Molecolare e Angiogenesi, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genova, Italy.
Luca MastracciAnatomia Patologica, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genova, Italy.
Federica GrilloAnatomia Patologica, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genova, Italy.
Mark Jon OlsenDepartment of Pharmaceutical Sciences, Midwestern University, Campus Glendale, Glendale, AZ 85308, USA.
Paola BarboroClinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genova, Italy.ORCID 0000-0001-9074-9290
Alessandro PoggiSSD Oncologia Molecolare e Angiogenesi, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genova, Italy.ORCID 0000-0002-1860-430X
Nicoletta FerrariSSD Oncologia Molecolare e Angiogenesi, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genova, Italy.ORCID 0000-0002-6027-1035
Ospedale Policlinico San Martino · ITMidwestern University · US

Funding

Ministero fondo 5x1000 Enti della Ricerca Sanitaria 2014, 2015, 2016
6 · The paper itself

Abstract

Colorectal cancer's (CRC) ability to invade local tissues and lymph nodes and generate distant metastases is the key for TNM classification. Aspartate-β-hydroxylase (ASPH), a transmembrane protein that catalyzes Notch receptors and ligand activation, is involved in tumor invasion. Because Notch is involved in gut homeostasis, it could be a target for CRC therapy. ASPH mRNA and protein expression, promoter methylation and gene copy numbers were evaluated using the TCGA and CPTAC human CRC datasets. Using digital pathology, ASPH was scored in the luminal area (LM), center tumor (CT) and invasive margin (IM) of 100 human CRCs. The effect of ASPH targeting on invasiveness and viability was tested by siRNA knockdown and small molecule inhibitors (SMI). Bioinformatics analysis showed increased expression of ASPH mRNA and protein in CRC, paired with a decreased methylation profile. ASPH genetic gain or amplification was frequent (56%), while deletion was rare (0.03%). Digital pathology analysis showed that ASPH exerted its pathological activity in the invasive margin of the tumor, affecting invasive front morphology, tumor budding and patients' overall survival. In vitro, ASPH targeting by siRNA or SMI reduced cell invasion and growth and caused Notch-1 downregulation. This study demonstrates that ASPH targeting by specific inhibitors could improve CRC treatment strategies.

Indexed as

ASPHcell invasioncolorectal cancertumor budding

Identifiers

PMID32295249
PMCPMC7226058
OpenAlexW3016288684

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.