Zinc finger AN1-type containing 4 is a novel marker for predicting metastasis and poor prognosis in oral squamous cell carcinoma

J Clin Pathol. 2018 May;71(5):436-441. doi: 10.1136/jclinpath-2017-204770. Epub 2017 Oct 26.

Abstract

Aims: Head and neck cancer, including oral squamous cell carcinoma (OSCC), is the sixth most common cancer worldwide and has a high potential for locoregional invasion and nodal metastasis. Therefore, discovery of a useful molecular biomarker capable of predicting tumour progression and metastasis of OSCC is crucial. We have previously reported zinc finger AN1-type containing 4 (ZFAND4) as one of the most upregulated genes in recurrent OSCC using a cDNA microarray analysis. Although ZFAND4 has been shown to promote cell proliferation of gastric cancer, its expression and clinicopathological roles in OSCC remain unclear.

Methods: In this study, we examined ZFAND4 expression by immunohistochemistry in 214 cases of OSCC.

Results: High cytoplasmic expression of ZFAND4 was observed in 45 out of 214 (21%) patients with OSCC. Expression levels of ZFAND4 were strongly associated with metastasis to the lymph nodes (p=0.0429) and distant organs (p=0.0068). Cases with high expression of ZFAND4 had a significantly unfavourable prognosis compared with patients with low expression of ZFAND4 (p<0.0001). Furthermore, ZFAND4 overexpression was an independent poor prognostic factor for OSCC as determined by multivariate analysis using the Cox proportional hazards model (p<0.0001).

Conclusions: These results suggest that ZFAND4 is a useful marker for predicting metastasis and poor prognosis in patients with OSCC.

Keywords: ZFAND4; metastasis; oral cancer; prognosis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Squamous Cell / chemistry*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / secondary*
  • Carcinoma, Squamous Cell / therapy
  • Disease-Free Survival
  • Female
  • Head and Neck Neoplasms / chemistry*
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / pathology*
  • Head and Neck Neoplasms / therapy
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mouth Neoplasms / chemistry*
  • Mouth Neoplasms / mortality
  • Mouth Neoplasms / pathology*
  • Mouth Neoplasms / therapy
  • Multivariate Analysis
  • Neoplasm Proteins / analysis*
  • Proportional Hazards Models
  • Risk Factors
  • Squamous Cell Carcinoma of Head and Neck
  • Time Factors
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • Neoplasm Proteins
  • ZFAND4 protein, human