Expression and prognostic significance of placental growth factor in hepatocellular carcinoma and peritumoral liver tissue.
Vascular endothelial growth factor-targeted therapy is a promising treatment for hepatocellular carcinoma (HCC), but its clinical benefit is often accompanied by acquired resistance. In animal studies, antiplacental growth factor therapy is effective with less resistance. The role of placental growth factor (PlGF) in the progression of HCC is not clear. In our study, we used immunohistochemistry in tissue microarrays to investigate PlGF expression in tumor and peritumoral liver tissues from 105 patients with HCC. Intratumoral and peritumoral PlGF mRNA expression was analyzed in another cohort of 37 patients. Peritumoral PlGF expression was significantly higher than intratumoral PlGF expression (p < 0.001). Intratumoral PlGF expression was not associated with patients' overall survival (OS) or time to recurrence (TTR). However, peritumoral PlGF expression, which was associated with tumor size, presence of intrahepatic metastasis, TNM stage and Barcelona Clinic Liver Cancer stage, was an independent risk factor for OS (p = 0.026) and TTR (p = 0.041). The prognostic value of peritumoral PlGF expression was further validated in a validation cohort (n = 394). We inferred that the elevation of PlGF in peritumoral liver might be induced by hypoxia. We found that peritumoral PlGF expression was associated with hypoxia-inducible factor-1α (p = 0.017). PlGF expression was elevated in L02, a hepatic cell line, under hypoxic conditions in vitro. These findings indicate that high peritumoral PlGF expression is associated with tumor recurrence and survival after resection of HCC. PlGF could be a target of adjuvant therapy and deserves further investigations.
Xu
Hua-Xiang
HX
Fudan University, Shanghai, People's Republic of China.
Zhu
Xiao-Dong
XD
Zhuang
Peng-Yuan
PY
Zhang
Ju-Bo
JB
Zhang
Wei
W
Kong
Ling-Qun
LQ
Wang
Wen-Quan
WQ
Liang
Ying
Y
Wu
Wei-Zhong
WZ
Wang
Lu
L
Fan
Jia
J
Tang
Zhao-You
ZY
Sun
Hui-Chuan
HC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000378:metabolism* / Q000601:surgery; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008024:Ligands; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000096:biosynthesis*; D011379:Prognosis
D008024:Ligands; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor