BACKGROUND: Under hypoxia, tumour cells undergo genetic and adaptive changes that allow their survival. Previously, we reported that high expression of hypoxia-inducible factor (HIF)-1 was a significant predictive factor for recurrence in hepatocellular carcinoma (HCC). Hypoxia also stimulates expression of procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) genes via the HIF-1 pathway. AIMS: The aim was to evaluate the relationship between hypoxia stress and expression of PLOD genes in HCC in vitro and to identify a new prognostic marker in HCC patients. METHODS: The PLOD2 expression was assessed under hypoxia in hepatoma cell lines and characterized in 139 HCC samples following hepatic resection using microarray experiments, quantitative RT-PCR and immunohistochemistry. Prognostic factors in HCC patients were assessed using univariate and multivariate analyses. RESULTS: The PLOD2 expression was induced under the hypoxia in vitro. Disease-free survival in the high PLOD2 expression group of HCC patients was significantly shorter when compared with the low-expression group (P = 0.002). In a subset of HCCs, we found that the PLOD2 expression of microarray was correlated with data of quantitative RT-PCR and immunohistochemistry. Of clinicopathological factors, PLOD2 expression was significantly correlated with tumour size (P = 0.022) and macroscopic intrahepatic metastasis (P = 0.049). In univariate analysis, six prognostic factors (tumour multiplicity, macroscopic intrahepatic metastasis, histological grade, microscopic portal invasion, microscopic intrahepatic metastasis and PLOD2 expression) were significant for disease-free survival. PLOD2 expression was identified as a significant, independent factor of poor prognosis (P = 0.013). CONCLUSIONS: PLOD2 is a potential novel prognostic factor for HCC patients following surgery.
BACKGROUND: Under hypoxia, tumour cells undergo genetic and adaptive changes that allow their survival. Previously, we reported that high expression of hypoxia-inducible factor (HIF)-1 was a significant predictive factor for recurrence in hepatocellular carcinoma (HCC). Hypoxia also stimulates expression of procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) genes via the HIF-1 pathway. AIMS: The aim was to evaluate the relationship between hypoxia stress and expression of PLOD genes in HCC in vitro and to identify a new prognostic marker in HCC patients. METHODS: The PLOD2 expression was assessed under hypoxia in hepatoma cell lines and characterized in 139 HCC samples following hepatic resection using microarray experiments, quantitative RT-PCR and immunohistochemistry. Prognostic factors in HCC patients were assessed using univariate and multivariate analyses. RESULTS: The PLOD2 expression was induced under the hypoxia in vitro. Disease-free survival in the high PLOD2 expression group of HCC patients was significantly shorter when compared with the low-expression group (P = 0.002). In a subset of HCCs, we found that the PLOD2 expression of microarray was correlated with data of quantitative RT-PCR and immunohistochemistry. Of clinicopathological factors, PLOD2 expression was significantly correlated with tumour size (P = 0.022) and macroscopic intrahepatic metastasis (P = 0.049). In univariate analysis, six prognostic factors (tumour multiplicity, macroscopic intrahepatic metastasis, histological grade, microscopic portal invasion, microscopic intrahepatic metastasis and PLOD2 expression) were significant for disease-free survival. PLOD2 expression was identified as a significant, independent factor of poor prognosis (P = 0.013). CONCLUSIONS:PLOD2 is a potential novel prognostic factor for HCC patients following surgery.
Authors: T S Karin Eisinger-Mathason; Minsi Zhang; Qiong Qiu; Nicolas Skuli; Michael S Nakazawa; Tatiana Karakasheva; Vera Mucaj; Jessica E S Shay; Lars Stangenberg; Navid Sadri; Ellen Puré; Sam S Yoon; David G Kirsch; M Celeste Simon Journal: Cancer Discov Date: 2013-08-01 Impact factor: 39.397
Authors: Daniele M Gilkes; Saumendra Bajpai; Carmen C Wong; Pallavi Chaturvedi; Maimon E Hubbi; Denis Wirtz; Gregg L Semenza Journal: Mol Cancer Res Date: 2013-02-01 Impact factor: 5.852
Authors: Roberto A Lleras; Richard V Smith; Leslie R Adrien; Nicolas F Schlecht; Robert D Burk; Thomas M Harris; Geoffrey Childs; Michael B Prystowsky; Thomas J Belbin Journal: Clin Cancer Res Date: 2013-07-26 Impact factor: 12.531
Authors: Daniel M Lewis; Hawley Pruitt; Nupur Jain; Mark Ciccaglione; J Michael McCaffery; Zhiyong Xia; Kristy Weber; T S Karin Eisinger-Mathason; Sharon Gerecht Journal: Cancer Res Date: 2019-02-18 Impact factor: 12.701