1. Academic Validation
  2. ZFX promotes tumorigenesis and confers chemotherapy resistance in esophageal squamous cell carcinoma

ZFX promotes tumorigenesis and confers chemotherapy resistance in esophageal squamous cell carcinoma

  • Clin Res Hepatol Gastroenterol. 2021 Sep;45(5):101586. doi: 10.1016/j.clinre.2020.101586.
Jingjing Wu 1 Yu Zhou 2 Tao Wang 2 Chao Jiang 2 Yong Gao 3 Bin Wei 4
Affiliations

Affiliations

  • 1 Department of Oncology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an 223300, China; Department of Hematology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an 223300, China.
  • 2 Department of Oncology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an 223300, China.
  • 3 Department of Oncology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an 223300, China. Electronic address: hayy_gy@163.com.
  • 4 Department of Oncology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an 223300, China. Electronic address: binweichn@yeah.net.
Abstract

Introduction: Zinc finger X-chromosomal protein (ZFX) has been shown to be essential for the development and progression of multiple types of human cancers. However, its potential roles in esophageal squamous cell carcinoma (ESCC) have not yet been elucidated.

Materials and methods: Eighty-three pairs of frozen ESCC samples and their para-cancer samples and 24 fresh ESCC samples were collected. In vitro chemosensitivity was tested using the histoculture drug response assay. Quantitative RT-PCR and western blotting were used to measure the expression of functional genes. The effects of ZFX on cell growth, cell Apoptosis, and chemosensitivity of the esophageal Cancer cells were assessed.

Results: We found that ZFX was more upregulated in ESCC tissues than in the para-cancer tissues, and its high expression was correlated with inferior clinicopathological characteristics and overall survival. Multivariate analysis revealed that ZFX was an independent prognostic factor in ESCC patients. In ESCC cell lines, ZFX silencing suppressed cell growth and induced cell Apoptosis. In addition, ZFX expression was negatively correlated with the sensitivity of fresh ESCC tissues to chemotherapeutic drugs, including cisplatin, docetaxel, fluorouracil, and irinotecan. Furthermore, the depletion of ZFX sensitized ESCC cells to cisplatin, and docetaxel treatment. Mechanistically, ZFX silencing resulted in the inactivation of the MEK/ERK pathway, which mediated the downregulation of P-glycoprotein expression.

Conclusion: Our study therefore indicates that ZFX possibly plays a critical role in ESCC tumorigenesis and chemotherapy resistance and could be a significant prognostic biomarker and therapeutic target for ESCC.

Keywords

Chemotherapy resistance; Esophageal squamous cell carcinoma; Prognosis; Tumorigenesis; ZFX.

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