Evidence map›Paper›PMID 32887625›Full record

ArticleJournal of translational medicine2020

Mass spectrometry-based analysis of formalin-fixed, paraffin-embedded distal cholangiocarcinoma identifies stromal thrombospondin-2 as a potential prognostic marker.

Johannes Byrling, Theresa Kristl, Dingyuan Hu, Indira Pla, Aniel Sanchez, Agata Sasor, Roland Andersson, György Marko-Varga, Bodil Andersson

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 7% 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, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

  1. Pooled it
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  8. Thrombospondin-2 as a diagnostic biomarker for distal cholangiocarcinoma and pancreatic ductal adenocarcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022
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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

9 authors at 1 institution in 1 country.

Johannes ByrlingDepartment of Clinical Sciences Lund, Surgery, Lund University, and Skåne University Hospital, Lund, Sweden.
Theresa KristlDepartment of Biomedical Engineering, Clinical Protein Science and Imaging, Lund University, Lund, Sweden.
Dingyuan HuDepartment of Clinical Sciences Lund, Surgery, Lund University, and Skåne University Hospital, Lund, Sweden.
Indira PlaDepartment of Biomedical Engineering, Clinical Protein Science and Imaging, Lund University, Lund, Sweden.
Aniel SanchezDepartment of Biomedical Engineering, Clinical Protein Science and Imaging, Lund University, Lund, Sweden.
Agata SasorDepartment of Clinical Sciences Lund, Pathology, Lund University, and Skåne University Hospital, Lund, Sweden.
Roland AnderssonDepartment of Clinical Sciences Lund, Surgery, Lund University, and Skåne University Hospital, Lund, Sweden.
György Marko-VargaDepartment of Biomedical Engineering, Clinical Protein Science and Imaging, Lund University, Lund, Sweden.
Bodil AnderssonDepartment of Clinical Sciences Lund, Surgery, Lund University, and Skåne University Hospital, Lund, Sweden. bodil.andersson@med.lu.se.ORCID 0000-0001-5591-0659
Lund University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDistal cholangiocarcinoma is an aggressive malignancy with a dismal prognosis. Diagnostic and prognostic biomarkers for distal cholangiocarcinoma are lacking. The aim of the present study was to identify differentially expressed proteins between distal cholangiocarcinoma and normal bile duct samples.

methodsA workflow utilizing discovery mass spectrometry and verification by parallel reaction monitoring was used to analyze surgically resected formalin-fixed, paraffin-embedded samples from distal cholangiocarcinoma patients and normal bile duct samples. Bioinformatic analysis was used for functional annotation and pathway analysis. Immunohistochemistry was performed to validate the expression of thrombospondin-2 and investigate its association with survival.

resultsIn the discovery study, a total of 3057 proteins were identified. Eighty-seven proteins were found to be differentially expressed (q < 0.05 and fold change ≥ 2 or ≤ 0.5); 31 proteins were upregulated and 56 were downregulated in the distal cholangiocarcinoma samples compared to controls. Bioinformatic analysis revealed an abundance of differentially expressed proteins associated with the tumor reactive stroma. Parallel reaction monitoring verified 28 proteins as upregulated and 18 as downregulated in distal cholangiocarcinoma samples compared to controls. Immunohistochemical validation revealed thrombospondin-2 to be upregulated in distal cholangiocarcinoma epithelial and stromal compartments. In paired lymph node metastases samples, thrombospondin-2 expression was significantly lower; however, stromal thrombospondin-2 expression was still frequent (72%). Stromal thrombospondin-2 was an independent predictor of poor disease-free survival (HR 3.95, 95% CI 1.09-14.3; P = 0.037).

conclusionSeveral proteins without prior association with distal cholangiocarcinoma biology were identified and verified as differentially expressed between distal cholangiocarcinoma and normal bile duct samples. These proteins can be further evaluated to elucidate their biomarker potential and role in distal cholangiocarcinoma carcinogenesis. Stromal thrombospondin-2 is a potential prognostic marker in distal cholangiocarcinoma.

Indexed as

Bile Duct NeoplasmsCholangiocarcinomaBile Ducts, IntrahepaticBiomarkers, TumorFormaldehydeHumansMass SpectrometryParaffin EmbeddingPrognosisThrombospondinsBiomarkers, TumorFormaldehydeThrombospondinsBiliary tract cancerBiomarkerDistal cholangiocarcinomaMass spectrometryParallel reaction monitoringStromaThrombospondin-2

Identifiers

PMID32887625
PMCPMC7487897
OpenAlexW3083622579

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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.