Evidence map›Paper›PMID 36589727›Full record

ArticleLiver cancer2022

Sulfatase-2 from Cancer Associated Fibroblasts: An Environmental Target for Hepatocellular Carcinoma?

Marco Y W Zaki, Sari F Alhasan, Ruchi Shukla, Misti McCain, Maja Laszczewska, Daniel Geh, Gillian L Patman, Despina Televantou, Anna Whitehead, João P Maurício and 15 more

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

Article in Liver cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.8field-weighted citation impact, top 17% 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

11 citing papers in PubMed, 19 citations in OpenAlex.

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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

25 authors at 4 institutions in 4 countries.

Marco Y W ZakiNewcastle University Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Sari F AlhasanNewcastle University Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Ruchi ShuklaNewcastle University Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Misti McCainNewcastle University Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Maja LaszczewskaNewcastle Fibrosis Research Group, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Daniel GehNewcastle University Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Gillian L PatmanNewcastle University Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Despina TelevantouNewcastle University Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Anna WhiteheadNewcastle University Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
João P MaurícioNewcastle University Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Ben BarksbyNewcastle Fibrosis Research Group, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Lucy M GeeNewcastle Fibrosis Research Group, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Hannah L PaishNewcastle Fibrosis Research Group, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Jack LeslieNewcastle Fibrosis Research Group, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Ramy YounesNewcastle University Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Alastair D BurtNewcastle University Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Lee A BorthwickNewcastle Fibrosis Research Group, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Huw ThomasNewcastle University Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Gary S BealeNewcastle University Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Olivier GovaereNewcastle University Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Daniela SiaDivision of Liver Diseases, Department of Medicine, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Quentin M AnsteeNewcastle University Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Dina TiniakosNewcastle University Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Fiona OakleyNewcastle Fibrosis Research Group, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Helen L ReevesNewcastle University Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Newcastle University · GBNewcastle upon Tyne Hospitals NHS Foundation Trust · GBNational and Kapodistrian University of Athens · GRTisch Hospital · US

Funding

Cancer Research UK 23390Cancer Research UK 26813Medical Research Council G0900535Medical Research Council MR/K001949/1Medical Research Council MR/R023026/1
6 · The paper itself

Abstract

Introduction: Heparin sulphate proteoglycans in the liver tumour microenvironment (TME) are key regulators of cell signalling, modulated by sulfatase-2 (SULF2). SULF2 overexpression occurs in hepatocellular carcinoma (HCC). Our aims were to define the nature and impact of SULF2 in the HCC TME. Methods: In liver biopsies from 60 patients with HCC, expression and localization of SULF2 were analysed associated with clinical parameters and outcome. Functional and mechanistic impacts were assessed with immunohistochemistry (IHC), in silico using The Cancer Genome Atlas (TGCA), in primary isolated cancer activated fibroblasts, in monocultures, in 3D spheroids, and in an independent cohort of 20 patients referred for sorafenib. IHC targets included αSMA, glypican-3, β-catenin, RelA-P-ser536, CD4, CD8, CD66b, CD45, CD68, and CD163. SULF2 impact of peripheral blood mononuclear cells was assessed by migration assays, with characterization of immune cell phenotype using fluorescent activated cell sorting. Results: We report that while SULF2 was expressed in tumour cells in 15% (9/60) of cases, associated with advanced tumour stage and type 2 diabetes, SULF2 was more commonly expressed in cancer-associated fibroblasts (CAFs) (52%) and independently associated with shorter survival (7.2 vs. 29.2 months, Conclusion: SULF2 derived from CAFs modulates glypican-3/β-catenin signalling but also the HCC immune TME, associated with tumour progression and therapy resistance via activation of the TAK1/IKKβ/NF-κB pathway. It is an attractive target for combination therapies for patients with HCC.

Indexed as

BiomarkersGlypican-3Hepatocellular carcinomaInflammationMetabolic diseaseMolecular targetsNASHSpheroidsSulfatase-2Tumour microenvironment

Identifiers

PMID36589727
PMCPMC9801184
OpenAlexW4285391624

What OpenQuestion holds

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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.