PLOD2 induced under hypoxia is a novel prognostic factor for hepatocellular carcinoma after curative resection.

Abstract

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: Takehiro Noda, Hirofumi Yamamoto, Ichiro Takemasa, Daisaku Yamada, Mamoru Uemura, Hiroshi Wada, Shogo Kobayashi, Shigeru Marubashi, Hidetoshi Eguchi, Masahiro Tanemura, Koji Umeshita, Yuichro Doki, Masaki Mori, Hiroaki Nagano
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 32 Issue 1 Pg. 110-8 (Jan 2012) ISSN: 1478-3231 [Electronic] United States
• PMID: 22098155 (Publication Type: Journal Article)
• Copyright: © 2011 John Wiley & Sons A/S.

Chemical References

• Biomarkers, Tumor
• PLOD2 protein, human
• Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase

Topics

• Biomarkers, Tumor (genetics, metabolism)
• Carcinoma, Hepatocellular (metabolism, mortality, secondary)
• Cell Hypoxia
• Cell Line, Tumor
• Disease-Free Survival
• Gene Expression Regulation, Neoplastic
• Hepatectomy
• Humans
• Japan (epidemiology)
• Liver Neoplasms (metabolism, mortality, pathology)
• Microarray Analysis
• Neoplasm Invasiveness
• Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase (biosynthesis, genetics)
• Survival Rate