Background: Hepatocellular carcinoma (HCC) tends to develop in the liver when there
is a high level of background inflammation (cirrhosis). Treatment options are limited and mainly
based on systemic therapies such as anti-angiogenic drugs (e.g. sorafenib). Connective tissue
growth factor (CTGF) is a matricellular protein involved in inflammation, tumour growth and
angiogenesis. The aim of this study is to determine the expression of CTGF and hypoxia inducible
factors (HIF) in HCC and to clarify its impact on relapse and survival.
Material and Methods: Eligibility criteria for the study consisted of patients with a diagnosis of HCC, formalin-fixed and
paraffin-embedded (FFPE) biopsy tissue, as well as relapse and available survival data. A tissue microarray was constructed
from ≥70% tumoural sections. The expressions of CTGF, HIF1α and HIF2α were analysed by immunohistochemistry.
The relationship between expression of CTGF/HIF1α and CTGF/HIF2α were analysed. Univariate and multivariate
analyses were performed.
Results: Fifty-three patients were screened; 39 patients were eligible for this study. Patients were treated with radical
intent. At the end of follow up, 59% patients relapsed (28.2% locally, 10.3% multicentric liver relapse and 7.7% distant
metastases). Estimated median disease-free survival (DFS) and overall survival (OS) were 23.4 (95%CI 7.18-39.66) and
38.6 months (95%CI 30.7-46.6), respectively. Expression of CTGF was: negative 23.1%, focal 48.7% and diffuse 23.1%.
A non-statistically significant relationship between expression of CTGF and HIF was shown supporting an alternative
pathway for CTGF expression in HCC. In multivariate analysis CTGF expression was an independent factor related to
OS, with shorter survival in those patients with focal/diffuse CTGF expression (HR 2.46; 95%CI 1.18-5.15).
Conclusions: Our results support that expression of CTGF is an independent factor associated with shorter OS in HCC.
Further analysis of CTGF expression in a larger series of HCC patients is required to confirm CTGF as a prognostic
biomarker in HCC.