Evidence map›Paper›PMID 37006231›Full record

ArticleFrontiers in immunology2023

Fueling the flames of colon cancer - does CRP play a direct pro-inflammatory role?

Anne Helene Køstner, Anniken Jørlo Fuglestad, Jeanette Baehr Georgsen, Patricia Switten Nielsen, Kristina Bang Christensen, Helle Zibrandtsen, Erik Thorlund Parner, Ibraheem M Rajab, Lawrence A Potempa, Torben Steiniche and 1 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

6 citing papers in PubMed, 6 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

11 authors at 6 institutions in 3 countries.

Anne Helene KøstnerCenter for Cancer Treatment, Sorlandet Hospital, Kristiansand, Norway.
Anniken Jørlo FuglestadCenter for Cancer Treatment, Sorlandet Hospital, Kristiansand, Norway.
Jeanette Baehr GeorgsenDepartment of Pathology, Aarhus University Hospital, Aarhus, Denmark.
Patricia Switten NielsenDepartment of Pathology, Aarhus University Hospital, Aarhus, Denmark.
Kristina Bang ChristensenDepartment of Pathology, Aarhus University Hospital, Aarhus, Denmark.
Helle ZibrandtsenDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Erik Thorlund ParnerSection for Biostatistics, Department of Public Health, Aarhus University, Aarhus, Denmark.
Ibraheem M RajabCollege of Science, Health and Pharmacy, Roosevelt University Schaumburg, Schaumburg, IL, United States.
Lawrence A PotempaCollege of Science, Health and Pharmacy, Roosevelt University Schaumburg, Schaumburg, IL, United States.
Torben SteinicheDepartment of Pathology, Aarhus University Hospital, Aarhus, Denmark.
Christian KerstenCenter for Cancer Treatment, Sorlandet Hospital, Kristiansand, Norway.
Aarhus University Hospital · DKAarhus University · DKRoosevelt University · USAkershus University Hospital · NOSørlandet Sykehus · NOUniversity of Bergen · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Systemic inflammation, diagnostically ascribed by measuring serum levels of the acute phase reactant C-reactive protein (CRP), has consistently been correlated with poor outcomes across cancer types. CRP exists in two structurally and functionally distinct isoforms, circulating pentameric CRP (pCRP) and the highly pro-inflammatory monomeric isoform (mCRP). The aim of this pilot study was to map the pattern of mCRP distribution in a previously immunologically well-defined colon cancer (CC) cohort and explore possible functional roles of mCRP within the tumor microenvironment (TME). Methods: Formalin-fixed, paraffin-embedded (FFPE) tissue samples from 43 stage II and III CC patients, including 20 patients with serum CRP 0-1 mg/L and 23 patients with serum CRP >30 mg/L were immunohistochemically (IHC) stained with a conformation-specific mCRP antibody and selected immune and stromal markers. A digital analysis algorithm was developed for evaluating mCRP distribution within the primary tumors and adjacent normal colon mucosa. Results: mCRP was abundantly present within tumors from patients with high serum CRP (>30 mg/L) diagnostically interpreted as being systemically inflamed, whereas patients with CRP 0-1 mg/L exhibited only modest mCRP positivity (median mCRP per area 5.07‰ (95%CI:1.32-6.85) vs. 0.02‰ (95%CI:0.01-0.04), p<0.001). Similarly, tissue-expressed mCRP correlated strongly with circulating pCRP (Spearman correlation 0.81, p<0.001). Importantly, mCRP was detected exclusively within tumors, whereas adjacent normal colon mucosa showed no mCRP expression. Double IHC staining revealed colocalization of mCRP with endothelial cells and neutrophils. Intriguingly, some tumor cells also colocalized with mCRP, suggesting a direct interaction or mCRP expression by the tumor itself. Conclusion: Our data show that the pro-inflammatory mCRP isoform is expressed in the TME of CC, primarily in patients with high systemic pCRP values. This strengthens the hypothesis that CRP might not only be an inflammatory marker but also an active mediator within tumors.

Indexed as

Colonic NeoplasmsC-Reactive ProteinEndothelial CellsHumansPilot ProjectsProtein IsoformsTumor MicroenvironmentC-Reactive ProteinProtein Isoformsbiomarkerscolon cancerC-reactive protein (CRP)CRP isoformsimmunohistochemistry (IHC)monomeric CRPsystemic inflammationtumor microenvironment

Identifiers

PMID37006231
PMCPMC10065292
OpenAlexW4327735563

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.