CLONING AND EXPRESSION OF A DEVELOPMENTALLY-REGULATED TRANSCRIPT MXR7IN HEPATOCELLULAR-CARCINOMA - BIOLOGICAL SIGNIFICANCE AND TEMPOROSPATIAL DISTRIBUTION

Using the differential display method to analyze mRNA expression in he patocellular carcinoma (HCC) and nontumor livers, we cloned a full-len gth cDNA of 2263 bp, which was designated GTR2-2 and was identical wit h MXR7. The MXR7 mRNA was detected in 143 of 191 (74.8%) primary and r ecurrent HCCs taken from 154 patients but only in 5 (3.2%) nontumor li vers. MXR7 mRNA was detected in one of two hepatoblastomas but not in hepatocellular adenoma, cholangiocarcinoma, or metastatic carcinomas t o the liver. Tn human cancer of other anatomical sites, MXR7 mRNA was detected in low levels in one Wilms' tumor and in 4 of 40 gastric aden ocarcinomas but not in several other types of cancer and 21 nonhepatoc ellular human tumor cell lines examined. MXR7 mRNA was expressed in hi gh levels in the placenta, fetal liver, lung, and kidney, but it was u ndetectable in adult liver and was expressed in very low levels in adu lt lung and kidney. Our observations suggest that the MXR7 gene is reg ulated developmentally and expressed preferentially in HCC. To study i ts potential biological significance, we selected 113 patients who had unicentric primary HCC and had been followed for more than 4 years fo r further analysis. The MXR7 mRNA expression correlated closely with e levated serum alpha-fetoprotein (AFP) levels (88 versus 55%; P = 0.000 1) 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 wi th patient outcome. In HCC less than or equal to 3 cm, the frequency ( 77%) of MXR7 mRNA expression was significantly higher than that of ele vated serum AFP (43%; P < 0.007) and AFP mRNA expression in HCC (41%; P < 0.001). Thus, MXR7 may serve as a sensitive early tumor marker for HCC and warrants more study to better understand its biological funct ion.