SALL4 is a marker of poor prognosis in serous ovarian carcinoma promoting invasion and metastasis

Oncol Rep. 2016 Mar;35(3):1796-806. doi: 10.3892/or.2016.4545. Epub 2016 Jan 5.

Abstract

Spalt-like transcription factor 4 (SALL4) is a transcription factor which is able to regulate development and embryonic stem cell pluripotency, and it is also involved in some tumor progression. However, the role of SALL4 in serous ovarian carcinoma (SOC) is still controversial. In this study, we determined the SALL4 expression in ovarian carcinoma (OC) cell lines and SOC tissues, and explored the clinical value of SALL4 in SOC. The SALL4 mRNA and protein expression in OC cell lines were examined by real-time PCR and western blotting. The SALL4 protein expression of 91 SOC tissue samples were examined by immunohistochemistry, and the correlation with clinicopathologic features as well as the survivals of SOC patients were analyzed. The invasion potential of OC cells were determined by cytoskeleton immunofluorescence, wound-healing, Transwell and colony formation assays. Our study found SALL4 mRNA and protein were highly expressed in OC cell lines, especially in HO-8910PM. SALL4 protein was highly expressed in SOC tissues, and positively associated with advanced FIGO stage, high histological grade, lymph node involvement, distant metastasis, recurrence and death of SOC (all P<0.05). Survival analysis showed that high expression of SALL4 indicated poorer overall and progression-free survival (P<0.05). Univariate and multivariate analysis showed that SALL4 is an independent marker for prognosis prediction (P<0.05). SALL4 ectopic expression significantly increased the migration, invasion and proliferation capacity of OC cells. In contrast, inhibition of SALL4 markedly decreased these capacities in vitro. In addition, SALL4-interference changed critical signaling involved in cancer progression. In conclusion, SALL4 was highly expressed and correlated with poor prognosis in SOC patients, promoting invasion and metastasis of OC cells. SALL4 could be a novel molecular target and prognostic marker for SOC.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Cystadenocarcinoma, Serous / genetics*
  • Cystadenocarcinoma, Serous / pathology
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Prognosis
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics

Substances

  • Biomarkers, Tumor
  • SALL4 protein, human
  • Transcription Factors