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The prognostic role of FZD6 in esophageal squamous cell carcinoma patients

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Abstract

Background

Esophageal squamous cell carcinoma (ESCC) is a kind of cancer with heterogeneous biological characteristics, which is affected by a complex network of gene interactions. Identification of molecular biomarkers paves the way for individualized therapy based on gene expression profiles, which can overcome the heterogeneity of ESCC.

Methods

In this study, GSE20347, GSE23400 and GSE45670 datasets were retrieved from Gene Expression Omnibus (GEO) database, and the overlapping differentially expressed genes (DEGs) in three datasets were screened. Then the overlapping DEGs function was annotated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-enrichment analysis. The prognostic value of the top five KEGG pathway-related genes were further validated in The Cancer Genome Atlas (TCGA) database. After extensive statistical analysis, four genes (CDC25B, CXCL8, FZD6 and MCM4) were identified as potential prognostic markers. Among the four candidate genes, the prognostic value of FZD6 in ESCC patients has not been evaluated. Therefore, we finally used immunohistochemistry method to evaluate the effect of FZD6 on the prognosis of patients with ESCC. Additionally, we detected the expression level of FZD6 in ESCC cell line and normal esophageal epithelial cell line, and observed the cell viability of ESCC cell line after FZD6 knockdown.

Results

The results showed that the overexpression of FZD6 predicted poor overall survival (OS) (P = 0.005) and progression-free survival (PFS) (P = 0.004) in ESCC patients. COX regression analysis showed that N stage (P = 0.026) and FZD6 expression level (P = 0.001) were independent prognostic factors of OS for ESCC patients. Furthermore, compared with normal esophageal epithelial cell line, the up-regulation of FZD6 was detected in ESCC cell line. Knockdown of FZD6 could significantly inhibit the proliferation of ESCC cells (P < 0.001).

Conclusion

CDC25B, CXCL8, FZD6 and MCM4 were screened as candidate genes for prognosis assessment of patients with ESCC. The prognostic role of FZD6 in ESCC patients was confirmed in current study.

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Funding

This work was supported by the National Natural Science Foundation of China (81502094) and First-Class Discipline Construction Founded Project of NingXia Medical University and the School of Clinical Medicine (NXYLXK2017A05).

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Author notes

  1. J. Zhang, J.-L. Wang and C.-Y. Zhang contributed equally to this work.

Authors and Affiliations

  1. Graduate School, Ningxia Medical University, Yinchuan, 750004, Ningxia, China

    J. Zhang & J.-L. Wang

  2. The First Peoples Hospital of Yinchuan, Yinchuan, 750001, Ningxia, China

    J. Zhang

  3. Department of Radiation Oncology, General Hospital of Ningxia Medical University, No.804 Shengli Str., Yinchuan, 750004, Ningxia, China

    C.-Y. Zhang, R. Zhao & Y.-Y. Wang

  4. Department of Radiation Oncology, General Hospital of Chinese Armed Police Force Border Defence Force, Shenzhen, 518000, Guangdong, China

    C.-Y. Zhang

  5. Department of Thoracic Surgery, General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, China

    Y.-F. Ma

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  1. J. Zhang
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  2. J.-L. Wang
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Correspondence to Y.-Y. Wang.

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The study was reviewed and approved by the Ethics Committee of the General Hospital of Ningxia Medical University. All patients provided written informed consent, and the study was conducted in accordance with the Declaration of Helsinki.

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Zhang, J., Wang, JL., Zhang, CY. et al. The prognostic role of FZD6 in esophageal squamous cell carcinoma patients. Clin Transl Oncol 22, 1172–1179 (2020). https://doi.org/10.1007/s12094-019-02243-3

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