Clinicopathological and prognostic significance of Yes-associated protein expression in hepatocellular carcinoma and hepatic cholangiocarcinoma

Tumour Biol. 2016 Oct;37(10):13499-13508. doi: 10.1007/s13277-016-5211-y. Epub 2016 Jul 28.

Abstract

Hepatocellular carcinoma (HCC) and hepatic cholangiocarcinoma (CC) are the most aggressive malignancies with a poor prognosis in humans, and hepatic cholangiocarcinoma (CC) exhibits greater malignant behaviour. Yes-associated protein (YAP) is an important downstream target of the Hippo signalling pathway. As an oncogene, it plays a vital role in the occurrence and development of tumours. Our study focuses on the clinical significance of YAP protein expression in HCC and CC. Furthermore, we sought to explore the different survival rates between HCC and CC. A total of 137 patients with HCC and 122 with CC after resection were evaluated by immunohistochemistry for the expression of YAP. Our results showed that positive expression rates of YAP were more frequently noted in CC 67.2 % (82/122) than in HCC 56.9 % (78/137) (P = 0.024). High YAP expression in HCC and CC was significantly associated with tumour size (P < 0.001 and P = 0.019, respectively), liver cirrhosis (P = 0.002 and P = 0.009, respectively), vascular invasion (P = 0.047 and P = 0.018, respectively), multiplicity (P = 0.019 and P = 0.015, respectively), and intrahepatic metastasis (P = 0.015 and P = 0.047, respectively). Importantly, recurrence-free survival and disease-specific survival rates were lower in CC with high YAP expression than in HCC with high YAP expression (P < 0.001 and P < 0.001, respectively). Overall, high YAP expression was more frequently found in CC than in HCC, and YAP overexpression was associated with poor survival rates in patients with HCC and CC. Targeting YAP treatment requires further prospective investigations in larger patient populations.

Keywords: Hepatic cholangiocarcinoma; Hepatocellular carcinoma; Immunohistochemistry; Yes-associated protein(YAP).

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Bile Duct Neoplasms / metabolism
  • Bile Duct Neoplasms / pathology
  • Bile Duct Neoplasms / surgery
  • Bile Ducts, Intrahepatic / metabolism
  • Bile Ducts, Intrahepatic / pathology
  • Bile Ducts, Intrahepatic / surgery
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / secondary*
  • Carcinoma, Hepatocellular / surgery
  • Cholangiocarcinoma / metabolism
  • Cholangiocarcinoma / pathology*
  • Cholangiocarcinoma / surgery
  • Combined Modality Therapy
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / surgery
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology*
  • Neoplasm Recurrence, Local / surgery
  • Neoplasm Staging
  • Phosphoproteins / metabolism*
  • Prognosis
  • Signal Transduction
  • Survival Rate
  • Transcription Factors
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • Phosphoproteins
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human