Prognostic values of vascular endothelial growth factor and matrix metalloproteinase-2 in hepatocellular carcinoma after radiotherapy.
OBJECTIVE
Hepatocellular carcinoma (HCC) is a highly vascularized tumor. In this study, we investigated the prognostic and predictive values of proangiogenic factors in HCC patients receiving radiotherapy.


METHODS
Between September 2008 and December 2009, a total of 50 patients treated with radiotherapy were prospectively enrolled in this study. Serum and urine samples were collected <1 week before and after radiotherapy.


RESULTS
After completion of radiotherapy, serum vascular endothelial growth factor (VEGF)/platelet (Plt) levels were significantly increased (p < 0.01). Patients who experienced hepatic tumor recurrence outside the radiation field showed higher VEGF-A/Plt levels before and after radiotherapy than patients who did not (p = 0.04), whereas patients who had hepatic tumor recurrence inside the radiation field showed significantly higher matrix metalloproteinase (MMP)-2 levels after radiotherapy (p = 0.04). On multivariate analyses, a high level of either VEGF/Plt or MMP-2 (≥median) before radiotherapy was a significant independent prognostic factor for a worse progression-free survival (p = 0.04).


CONCLUSIONS
In HCC patients receiving radiotherapy, levels of VEGF/Plt and MMP-2 before radiotherapy can be useful to predict treatment outcome. This study also suggests the necessity of anti-angiogenic therapy, such as sorafenib, since radiotherapy increases VEGF/Plt levels, and higher levels of VEGF/Plt are associated with a poor outcome.
Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
Yang-Gun
YG
Suh
Eun-Jung
EJ
Lee
Hyejung
H
Cha
Seung-Hyun
SH
Yang
Jinsil
J
Seong
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000401:mortality / Q000532:radiotherapy*; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood / Q000401:mortality / Q000532:radiotherapy*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000652:urine*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D056910:Republic of Korea; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D020778:Matrix Metalloproteinase 2