Using the differential display method to analyze mRNA expression in hepatocellular carcinoma (HCC) and nontumor livers, we cloned a full-length cDNA of 2263 bp, which was designated GTR2-2 and was identical with MXR7. The MXR7 mRNA was detected in 143 of 191 (74.8%) primary and recurrent HCCs taken from 154 patients but only in 5 (3.2%) nontumor livers. MXR7 mRNA was detected in one of two hepatoblastomas but not in hepatocellular adenoma, cholangiocarcinoma, or metastatic carcinomas to the liver. In human cancer of other anatomical sites, MXR7 mRNA was detected in low levels in one Wilms' tumor and in 4 of 40 gastric adenocarcinomas but not in several other types of cancer and 21 nonhepatocellular human tumor cell lines examined. MXR7 mRNA was expressed in high levels in the placenta, fetal liver, lung, and kidney, but it was undetectable in adult liver and was expressed in very low levels in adult lung and kidney. Our observations suggest that the MXR7 gene is regulated developmentally and expressed preferentially in HCC. To study its potential biological significance, we selected 113 patients who had unicentric primary HCC and had been followed for more than 4 years for further analysis. The MXR7 mRNA expression correlated closely with elevated serum alpha-fetoprotein (AFP) levels (88 versus 55%; P = 0.0001) and with expression of AFP mRNA (87 versus 55%; P = 0.005) and CD24 mRNA in HCC (80 versus 50%; P < 0.04), high tumor grade (76 versus 56%; P = 0.05), and tumor invasion (76 versus 55%; P < 0.05), but not with patient outcome. In HCC < or =3 cm, the frequency (77%) of MXR7 mRNA expression was significantly higher than that of elevated serum AFP (43%; P < 0.007) and AFP mRNA expression in HCC (41%; P < 0.004). Thus, MXR7 may serve as a sensitive early tumor marker for HCC and warrants more study to better understand its biological function.