Evidence map›Paper›PMID 33824478›Full record

ArticleBritish journal of cancer2021

α-Fetoprotein mRNA in situ hybridisation is a highly specific marker of hepatocellular carcinoma: a multi-centre study.

Shi-Xun Lu, Yu-Hua Huang, Li-Li Liu, Chris Zhiyi Zhang, Xia Yang, Yuan-Zhong Yang, Chun-Kui Shao, Jian-Ming Li, Dan Xie, Xuchen Zhang and 2 more

Open access · hybridAbstract readValidation Study
In one paragraph

Article in British journal of cancer, 2021. 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
2.7field-weighted citation impact, top 8% 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, 20 citations in OpenAlex.

  1. Article
  2. Exposure to low levels of hexavalent chromium in drinking water alters diet-induced steatotic liver disease in male rats.Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) · 2025
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  6. mJournal of hepatocellular carcinoma · 2024
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  8. Review
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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

12 authors at 3 institutions in 2 countries.

Shi-Xun Lu *Department of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Yu-Hua Huang *Department of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Li-Li Liu *Department of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Chris Zhiyi ZhangKey Laboratory of Functional Protein Research of Guangdong Higher Education Institutes and MOE Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China.
Xia YangDepartment of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Yuan-Zhong YangDepartment of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Chun-Kui ShaoDepartment of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Jian-Ming LiDepartment of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Dan XieDepartment of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Xuchen ZhangDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Dhanpat JainDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Jing-Ping YunDepartment of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. yunjp@sysucc.org.cn.ORCID http://orcid.org/0000-0002-1001-0769
Sun Yat-sen University · CNYale University · USJinan University · CN

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Liver CenterP30DK034989 · NIDDK · YALE UNIVERSITY · PI YASUKO IWAKIRI · 1986 to 2026
$31.1M
NCATS NIH HHS UL1 TR001863NIDDK NIH HHS P30 DK034989
6 · The paper itself

Abstract

backgroundPathologic diagnosis of hepatocellular carcinoma (HCC) can be challenging in differentiating from benign and non-hepatocytic malignancy lesions. The aim of this study was to investigate the potential utility of α-fetoprotein (AFP) mRNA RNAscope, a sensitive and specific method, in the diagnosis of HCC.

methodsThree independent retrospective cohorts containing 2216 patients with HCC, benign liver lesions, and non-hepatocytic tumours were examined. AFP was detected using ELISA, IHC (Immunohistochemistry), and RNAscope. Glypican3 (GPC3), hepatocyte paraffin-1 (HepPar-1), and arginase-1 (Arg-1) proteins were detected using IHC.

resultsAFP RNAscope improved the HCC detection sensitivity by 24.7-32.7% compared with IHC. In two surgical cohorts, a panel of AFP RNAscope and GPC3 provided the best diagnostic value in differentiating HCC from benign hepatocytic lesions (AUC = 0.905 and 0.811), and a panel including AFP RNAscope, GPC3, HepPar-1, and Arg-1 yielded the best AUC (0.971 and 0.977) when distinguishing HCC from non-hepatocytic malignancies. The results from the liver biopsy cohort were similar, and additional application of AFP RNAscope improved the sensitivity by 18% when distinguishing HCC from benign hepatocytic lesions.

conclusionsAFP mRNA detected by RNAscope is highly specific for hepatocytic malignancy and may serve as a novel diagnostic biomarker for HCC.

Indexed as

alpha-FetoproteinsBiomarkers, TumorCarcinoma, HepatocellularCohort StudiesDiagnosis, DifferentialHumansImmunohistochemistryIn Situ HybridizationLiver NeoplasmsPredictive Value of TestsRetrospective StudiesRNA, MessengerSensitivity and SpecificityTissue Array AnalysisAFP protein, humanalpha-FetoproteinsBiomarkers, TumorRNA, Messenger

Identifiers

PMID33824478
PMCPMC8184895
OpenAlexW3150773867

What OpenQuestion holds

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Registered trials

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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.