Elevated plasma osteopontin levels in patients with hepatocellular carcinoma.
OBJECTIVE
Osteopontin (OPN) is a secreted glycoprotein, frequently associated with various tumors. We investigated the usefulness of plasma OPN level as a biomarker for hepatocellular carcinoma (HCC).


METHODS
We determined plasma levels of OPN, alpha-fetoprotein (AFP), and prothrombin induced by vitamin K absence II (PIVKA II) in a group of 62 HCC patients, in 60 patients with chronic liver diseases, and in 60 healthy control individuals using a standardized ELISA kit. To determine the source of elevated plasma level of OPN, immunohistochemical analysis of 285 HCC samples on tissue microarray was performed.


RESULTS
Plasma OPN levels in the HCC patients (median 954 ng/mL, range 168-5,742) were significantly higher (p-value < 0.001) than those patients with chronic liver diseases (381 ng/mL, 29-1,688) or of a healthy control group (155 ng/mL, 10-766). Within the HCC patient group, plasma OPN level increased significantly with advancing degree of Child-Pugh class and of tumor stage. Diagnostic sensitivity and specificity of OPN for HCC was 87% and 82%, respectively (cut-off value: 617.6 ng/mL). OPN had a greater area under curve value (0.898) than AFP (0.745) or PIVKA II (0.578), suggesting superior diagnostic accuracy of OPN. Immunohistochemistry of 285 samples of HCC showed that OPN was expressed in 92 of 285 tumors (32.3%). OPN expression was found in the malignant hepatocytes and cancer-infiltrating macrophages, not in the noncancerous hepatocytes or Kupffer cells.


CONCLUSIONS
These data propose elevated plasma OPN levels as a potential biomarker for HCC.
Kim
Jin
J
Department of Internal Medicine, Korea Institute of Radiological and Medical Sciences, Gongneung-dong, Nowon-ku, Seoul, Korea.
Ki
Seung S
SS
Lee
Sang D
SD
Han
Chul J
CJ
Kim
Yu C
YC
Park
Sun H
SH
Cho
Soo Y
SY
Hong
Young-Joon
YJ
Park
Hyo Y
HY
Lee
Myoungjin
M
Jung
Ha H
HH
Lee
Kee H
KH
Jeong
Sook-Hyang
SH
D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000473:pathology / Q000601:surgery; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006498:Hepatectomy; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D053495:Osteopontin; D010750:Phosphoproteins / Q000097:blood*; D011379:Prognosis; D011498:Protein Precursors / Q000097:blood; D011516:Prothrombin; D012372:ROC Curve; D012720:Severity of Illness Index; D012795:Sialoglycoproteins / Q000097:blood*; D000509:alpha-Fetoproteins / Q000378:metabolism
D015415:Biomarkers; D014408:Biomarkers, Tumor; D010750:Phosphoproteins; D011498:Protein Precursors; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D000509:alpha-Fetoproteins; D053495:Osteopontin; C008208:acarboxyprothrombin; D011516:Prothrombin