Evidence map›Paper›PMID 38815632›Full record

ArticleBiochemical pharmacology2024

Relaxin-2 is a novel biomarker for differentiated thyroid carcinoma in humans.

Anupam Kotwal, Ronda Simpson, Nicholas Whiteman, Benjamin Swanson, Ana Yuil-Valdes, Madelyn Fitch, Joshua Nguyen, Salma Elhag, Oleg Shats, Whitney Goldner and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochemical pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Role of Relaxin Signaling in Cancer: A Review.Biochemical pharmacology · 2024
    Review
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.

Anupam KotwalDepartment of Internal Medicine, Division of Diabetes, Endocrinology, and Metabolism, University of Nebraska Medical Center, Omaha, NE, USA; VA Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
Ronda SimpsonVA Nebraska-Western Iowa Health Care System, Omaha, NE, USA.
Nicholas WhitemanDepartment of Internal Medicine, Division of Diabetes, Endocrinology, and Metabolism, University of Nebraska Medical Center, Omaha, NE, USA.
Benjamin SwansonBuffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA; Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA.
Ana Yuil-ValdesBuffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA; Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA.
Madelyn FitchDepartment of Internal Medicine, Division of Diabetes, Endocrinology, and Metabolism, University of Nebraska Medical Center, Omaha, NE, USA.
Joshua NguyenDepartment of Internal Medicine, Division of Diabetes, Endocrinology, and Metabolism, University of Nebraska Medical Center, Omaha, NE, USA.
Salma ElhagDepartment of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA.
Oleg ShatsBuffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
Whitney GoldnerDepartment of Internal Medicine, Division of Diabetes, Endocrinology, and Metabolism, University of Nebraska Medical Center, Omaha, NE, USA; Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
Robert BennettDepartment of Internal Medicine, Division of Diabetes, Endocrinology, and Metabolism, University of Nebraska Medical Center, Omaha, NE, USA; VA Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA. Electronic address: rgbennet@unmc.edu.

Funding

Tracking and Evaluation CoreU54GM115458 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI ESTABROOKS, PAUL · 2016 to 2025
$42.8M
The Role of Relaxin Signaling in Adipose Tissue Fibrosis and FunctionI01BX005687 · VA · OMAHA VA MEDICAL CENTER · PI ROBERT G BENNETT · 2022 to 2026
–
BLRD VA I01 BX005687NIGMS NIH HHS U54 GM115458
6 · The paper itself

Abstract

Relaxin's role in differentiated thyroid cancer (DTC) has been suggested but its characterization in a large clinical sample remains limited. We performed immunohistochemistry for relaxin-2 (RLN2), CD68 (total macrophages), CD163 (M2 macrophages) on tissue microarrays from 181 subjects with non-distant metastatic DTC, and 185 subjects with benign thyroid tissue. Mean pixels/area for each marker was compared between tumor and adjacent tissue via paired-t test and between DTC and benign subjects via t-test assuming unequal variances. RNA qPCR was performed for expression of RLN2, RLN1, and RXFP1 in cell lines. Amongst 181 cases, the mean age was 46 years, 75 % were females. Tumoral tissue amongst the DTC cases demonstrated higher mean expression of RLN2 (53.04 vs. 9.79; p < 0.0001) compared to tumor-adjacent tissue. DTC tissue also demonstrated higher mean expression of CD68 (14.46 vs. 4.79; p < 0.0001), and CD163 (23.13 vs. -0.73; p < 0.0001) than benign thyroid. These markers did not differ between tumor-adjacent and benign thyroid tissue groups; and amongst cases, did not differ by demographic or clinicopathologic features. RLN1 and RXFP1 expression was detected in a minority of the cell lines, while RLN2 was expressed by 6/7 cell lines. In conclusion, widespread RLN2 expression in DTC tissue and most cell lines demonstrates that RLN2 acts in a paracrine manner, and that RLN1 and RXFP1 are probably not involved in thyroid cancer cell signaling. RLN2 is a biomarker for thyroid carcinogenesis, being associated with but not secreted by immunosuppressive macrophages. These findings will guide further investigations for therapeutic avenues against thyroid cancer.

Indexed as

Biomarkers, TumorRelaxinThyroid NeoplasmsAdultAgedAntigens, CDAntigens, Differentiation, MyelomonocyticCell Line, TumorFemaleHumansMaleMiddle AgedReceptors, G-Protein-CoupledReceptors, PeptideAntigens, CDAntigens, Differentiation, MyelomonocyticBiomarkers, TumorReceptors, G-Protein-CoupledReceptors, PeptideRelaxinRLN2 protein, humanRXFP1 protein, humanCarcinogenesisMacrophagesRelaxinThyroid carcinomaTumor microenvironment

Identifiers

PMID38815632
PMCPMC11470803

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.