SALL4 is a novel therapeutic target in intrahepatic cholangiocarcinoma

Oncotarget. 2015 Sep 29;6(29):27416-26. doi: 10.18632/oncotarget.4862.

Abstract

Intrahepatic cholangiocarcinoma (ICC) is the most common and deadly disease of the biliary tree due to its poor prognosis. Sal-like protein 4 (SALL4), a stem cell marker, has been identified as a potential target for aggressive hepatocellular carcinoma (HCC). In our study, 175 ICC cases with an average age of 55 years were included, and 53% (93/175) were male. And 28 adjacent non-tumor tissues were also collected. The SALL4-positive immunoreactivity was detected in a total of 102 ICC cases (58%), whereas all 28 adjacent tissues showed negative staining. Univariate analysis, showed that the SALL4-positive ICC cases had significantly more frequent lymph nodal metastasis (P = 0.0460), vascular invasion (P < 0.0001), and nerve invasion (P < 0.0001). Furthermore, the strong SALL4-positive cases (n = 7, 5 months) had shorter overall survival, when compared to moderate SALL4-positive (n = 46, 9 months) or SALL4-negative cases (n = 73, 7 months), respectively. Our data also suggest that SALL4 may be involved in the regulation of epithelial-mesenchymal transition (EMT) in ICC. Those results for the first time indicate an oncogenic role of SALL4 in ICC. Therefore, SALL4 may serve as a promising therapeutic target for ICC.

Keywords: SALL4; intrahepatic cholangiocarcinoma; invasion; migration; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Tumor-Associated, Carbohydrate / metabolism
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / therapy
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cholangiocarcinoma / metabolism*
  • Epithelial-Mesenchymal Transition
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / metabolism
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / therapy
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / metabolism*
  • Treatment Outcome
  • Wound Healing

Substances

  • Antigens, Tumor-Associated, Carbohydrate
  • Biomarkers, Tumor
  • Ki-67 Antigen
  • SALL4 protein, human
  • Transcription Factors
  • carbohydrate antigen 199, human