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Association of insulin-like growth factor binding protein-7 promoter methylation with esophageal cancer in peripheral blood

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Abstract

Background

The insulin-like growth factor (IGF) signaling pathway has an important role in many cancers, including esophageal cancer (EC). IGF-binding protein 7 (IGFBP7) is one of the proteins in this signaling pathway, and its role in cancer has not yet been fully clarified. In the present study, we evaluated the clinical relevance of IGFBP7 methylation status and mRNA expression in EC patients compared to healthy controls. We also investigated whether IGFBP7 methylation status affects mRNA expression.

Methods

The study comprised 100 EC patients and 105 healthy controls. Methylation specific PCR (MSP) was used to examine IGFBP7's promoter methylation and real-time quantitative reverse transcription PCR (qRT-PCR) was used to assess IGFBP7 mRNA expression.

Results

The IGFBP7 promoter methylation was significantly higher in controls than in EC patients (p < 0.05). IGFBP7 mRNA expression was significantly lower in EC patients compared to controls, especially in those over 55 years old (p < 0.0001). The globulin level and reflux were significantly higher in IGFBP7-unmethylated patients compared to IGFBP7 methylated patients (p = 0.01). In EC patients, however, there was no significant relationship between IGFBP7 mRNA expression and methylation in the peripheral blood (p = 0.33). In addition, neither IGFBP7 mRNA expression nor methylation were shown to be linked with survival (p > 0.05).

Conclusion

Our study indicated that promoter unmethylation and mRNA expression of the IGFBP7 promoter in peripheral blood could be different biomarkers for EC. Furthermore, unmethylation of the IGFBP7 promoter in EC patients was associated with reflux and elevated globulin levels. More studies with a larger number of cases is needed to confirm this association.

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Abbreviations

IGF:

Insulin-like growth factor

IGFBP7:

IGF-binding protein 7

IGFBP-rp:

IGFBP-related protein

EC:

Esophageal cancer

qRT-PCR:

Real-time quantitative reverse transcription polymerase chain reaction

MSP:

Methylation specific PCR

ESCC:

Esophageal squamous cell carcinoma

EAC:

Esophageal adenocarcinoma

WHO:

World Health Organization

AFP:

Alfa feta protein

M:

Methylation

U:

Unmethylation

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Funding

This work was supported by grants from the Research Foundation of Van Yüzüncü Yıl University (BAP) (TSA-2018-6583).

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Authors and Affiliations

  1. Department of Medical Biology, Faculty of Medicine, Van Yüzüncü Yıl University, Van, Turkey

    Zehra Kaya, Elif Sena Sahin & Seren Duran

  2. Department of General Surgery, Faculty of Medicine, Van Yüzüncü Yıl University, Van, Turkey

    Necat Almalı

  3. Department of Medical Genetics, Faculty of Medicine, Van Yüzüncü Yıl University, Van, Turkey

    Gökhan Görgisen

  4. Department of Biostatistics, Faculty of Medicine, Aksaray University, Aksaray, Turkey

    Can Ates

Authors
  1. Zehra Kaya
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  2. Necat Almalı
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  5. Gökhan Görgisen
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Corresponding author

Correspondence to Zehra Kaya.

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Conflict of interest

The authors declare that there are no conflicts of interest.

Ethical approval

The study has been approved by the ethics committee of SBU Van Education and Research Hospital (Approval Number: 2017/7, Approval Date: September 28, 2017) with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all study participants.

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Kaya, Z., Almalı, N., Sahin, E.S. et al. Association of insulin-like growth factor binding protein-7 promoter methylation with esophageal cancer in peripheral blood. Mol Biol Rep 49, 3423–3431 (2022). https://doi.org/10.1007/s11033-022-07173-y

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