Overexpression of S100A14 contributes to malignant progression and predicts poor prognosis of lung adenocarcinoma

Thorac Cancer. 2018 Jul;9(7):827-835. doi: 10.1111/1759-7714.12654. Epub 2018 May 7.

Abstract

Background: S100A14 is a member of the S100 calcium-binding protein family that exerts important phenotypic effects on cell proliferation, apoptosis, differentiation, and motility. However, the functional role and potential clinical significance of S100A14 in lung adenocarcinoma has not yet been clarified.

Methods: We analyzed genomic alterations of S100A14 using The Cancer Genome Atlas lung adenocarcinoma genomic dataset. S100A14 displayed significant copy number amplification in lung adenocarcinoma. We detected S100A14 expression in lung adenocarcinoma and analyzed the correlation between S100A14 expression and clinicopathological characteristics.

Results: Immunohistochemical analysis showed that S100A14 expression was obviously upregulated in lung adenocarcinoma tissues compared to matched normal counterparts. Statistical analysis revealed that S100A14 expression strongly correlated with poor differentiation, metastasis, stage, smoking, and EGFR mutation. Furthermore, our data indicated that S100A14 serum levels were higher in lung adenocarcinoma patients than healthy controls. Intriguingly, S100A14 serum levels were related to distant metastasis (P = 0.028). High S100A14 expression was significantly associated with overall (P = 0.0016) and post progression (P = 0.039) survival. In addition, we investigated the biological functions of S100A14 in lung adenocarcinoma cell lines. The results demonstrated that S100A14 promoted cell migration and invasion of SPCA1 and Glc-82 cells.

Conclusions: S100A14 increases the motility of lung adenocarcinoma cells, and might be a diagnostic and prognostic serum biomarker and potential therapeutic target for lung adenocarcinoma.

Keywords: Diagnosis; S100A14; lung adenocarcinoma; metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / blood*
  • Adenocarcinoma of Lung / epidemiology
  • Adenocarcinoma of Lung / pathology
  • Adult
  • Aged
  • Apoptosis / genetics
  • Biomarkers, Tumor / blood*
  • Calcium-Binding Proteins / blood*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis / genetics
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis*

Substances

  • Biomarkers, Tumor
  • Calcium-Binding Proteins
  • S100A14 protein, human