Purpose:
Olfactomedin 4 (OLFM4) is a secreted glycoprotein predominantly expressed in bone
marrow and gastrointestinal tract. Aberrant expression of OLFM4 in human cancers has
been reported, but its biological function and significance remain poorly understood
in hepatocellular carcinoma (HCC). The purpose of this study is to examine the expression
pattern of OLFM4 and its prognostic significance in patients with HCC.
Experimental design:
Immunohistochemical staining to assess expression and cellular distribution of OLFM4
was performed by using a tissue micro array comprising HCC tissues and matched non-tumor
tissues from 157 HCC patients. Clinicopathologic characteristics and survival were
analysed in 95 patients who underwent partial hepatectomy.
Results:
The fraction of HCC samples exhibiting positive OLFM4 staining in both cytoplasm and
membrane was higher in comparison to that observed in hepatocytes from matched non-tumour
tissue (61% vs. 39%). Cytoplasmic staining for OLFM4 was associated with poorer survival
(p = 0.008), vascular invasion (p = 0.048) and MMP-7 expression (p = 0.002). Multivariate
analysis confirmed that cytoplasmic staining of OLFM4 is significantly correlated
with poorer 5-year survival {58.3 vs. 17.3%; HR: 2.135 [95% confidence interval (CI),
1,135 – 4.015]; p = 0.019}.
Conclusion:
Expression of OLFM4 is associated with poorer survival and markers of invasive growth,
indicating that this protein might play an important role in determining the aggressiveness
of HCC and might serve as a prognostic marker.
