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The role of Wnt pathway antagonists in early-stage lung adenocarcinoma

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Abstract

Purpose

We aimed to examine the expression levels of the genes encoding adenomatous polyposis coli (APC) 1, APC-2, Dickkopf related protein (DKK)-1, DKK-3, secreted frizzled-related protein (SFRP)-2, SFRP-4, and SFRP-5, which play roles in the Wnt signaling pathway, in lung adenocarcinoma and adjacent normal lung tissues and to evaluate their relationships with clinicopathologic factors.

Materials and methods

The expression levels of genes in formalin-fixed paraffin-embedded samples of tumor tissue and adjacent intact lung tissue from 57 patients who underwent surgery for lung adenocarcinoma between 2011 and 2018 were determined by real-time PCR analysis.

Results

The expression levels of the DKK-1 in tumor tissue, especially in stage I–II tumor tissue, were significantly suppressed compared to those in normal tissue (p < 0.025). Whereas DKK-1 expression was suppressed in the tumor tissue of patients with early-stage lung adenocarcinoma, expression of the SFRP-5 in these patients was significantly higher in tumor tissue than in normal tissue (p < 0.039).

Conclusion

In our study, opposing regulation was found between the SFRP-5 and DKK-1, which are known to be extracellular antagonists of the Wnt signaling pathway. The SFRP-5 was found to have an oncogenic role in adenocarcinoma development. Studies of the opposing regulation between these genes in early-stage lung adenocarcinoma may shed light on the mechanisms associated with the development of carcinogenesis. The relationships or interactions of these genes may serve as potential therapeutic targets.

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Abbreviations

SFRP:

Secreted frizzled-related protein

DKK:

Dickkopf-related protein

FZD:

Frizzled receptor

GSK3β:

Glycogen synthase kinase 3 beta

LRP:

Lipoprotein receptor-related protein

NSCLC:

Non-small cell lung cancer

APC:

Adenomatous polyposis coli

DVL:

Disheveled-related protein

CK1α:

Casein-kinase 1α protein

WIF:

Wnt inhibitory factor

CSC:

Cancer stem cell

EMT:

Epithelial-to-mesenchymal transition

JNK:

C-Jun N-terminal kinase protein

RYK:

Receptor tyrosine kinase protein

ROS:

Reactive oxygen species

ROR:

Receptor tyrosine kinase-like orphan receptor

AXIN:

Axis inhibition protein

TKI:

Tyrosine kinase receptor inhibitor

EGFR:

Epidermal growth factor receptor

BAX:

BCL2-associated X

Bcl-2:

B-cell lymphoma

KEGG:

Kyoto encyclopedia of genes and genomes

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Funding

This work was supported by Mugla Sıtkı Koçman University (Project Number 19/087/07/3/4).

Author information

Authors and Affiliations

  1. Department of Thoracic Surgery, Medical Faculty, School of Medicine, Mugla Sıtkı Kocman University, Mugla, Turkey

    Arife Zeybek

  2. Department of Thoracic Surgery, Private Antalya Med-Star Hospital, Antalya, Turkey

    Necdet Öz

  3. Department of Chest Disease, Kocaeli Medikal Park Hospital, Kocaeli, Turkey

    Serdar Kalemci

  4. School of Science, Siena College, New York, USA

    Kürşad Tosun

  5. Department of Medical Biology, Medical Faculty, Mugla Sıtkı Kocman University, Mugla, Turkey

    Tuba Gökdoğan Edgünlü

  6. Department of Medical Biology, Mersin University Medical Faculty, Mersin, Turkey

    Mehmet Tuğhan Kızıltuğ & Mehmet Emin Erdal

  7. Department of Medical Pathology, Medical Faculty, Mugla Sıtkı Kocman University, Mugla, Turkey

    Leyla Tekin

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  1. Arife Zeybek
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Contributions

AZ: project administration, investigation, writing—original draft. NÖ: data curation, resources. SK: data curation, resources, English editing. KT: formal analysis. GTE: writing, review, editing. TMK: resources, analysis. LT: resources. EME: conceptualization, methodology.

Corresponding author

Correspondence to Arife Zeybek.

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Conflict of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethical approval

All procedures performed in our study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards The study protocol (no. 169) was approved by the Ethics Committee of Human Investigations of Muğla Sıtkı Koçman University on 13.12.2018.Declaration of competing interests.

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Zeybek, A., Öz, N., Kalemci, S. et al. The role of Wnt pathway antagonists in early-stage lung adenocarcinoma. Mol Biol Rep 49, 9–17 (2022). https://doi.org/10.1007/s11033-021-06759-2

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