[Overexpression and genomic amplification of decoy receptor 3 in hepatocellular carcinoma and significance thereof].
OBJECTIVE
To investigate the mRNA expression and genomic amplification of decoy receptor 3 (DcR3) in hepatocellular carcinoma (HCC) and the significance thereof.


METHODS
RT-PCR was used to examine the expression of DcR3 mRNA in 48 cases of HCC tissues and the normal tissues adjacent to the tumor resected in operation and proved pathologically. The DcR3 gene amplification in the cancer tissues was examined by quantitative genomic PCR. The correlation between the DcR3 mRNA expression and genomic amplification of HCC was analyzed statistically. The differences in DcR3 expression and amplification in HCC with different clinical and pathological features were compared.


RESULTS
DcR3 mRNA was detected in 29 out of the 48 HCC cases with a positive rate of 60.4%. No DcR3 mRNA expression was detected in the 48 cases of normal tissues adjacent to tumor. DcR3 mRNA was expressed significantly higher in HCC > 5 mm, at stages and, and with infiltration and metastasis than those <or= 5 cm, at early stages, or without infiltration and metastasis (all P < 0.05). The expression of DcR3 was not related to the existence of membrane of tumor or cancer embolus, and the number of masses (all P > 0.05). The DcR3 gene amplification in 48 cases of HCC ranges from 0.18 to 3.86-fold. Seven of the 48 cases of HCC showed significantly higher DcR3 gene amplification than the normal control tissues. The positive rate of DcR3 mRNA expression was 40% in the 25 HCC patients with the amplification fold < 1.0 (10/25), significantly lower than that in the 23 patients with the amplification fold > 1.0 (82.6%, 19/23), P < 0.01. The average DcR3 gene amplification fold was 1.53 +/- 0.82 in the patients with positive mRNA expression, significantly higher than that in those with negative expression (0.75 +/- 0.33, P < 0.01). The DcR3 gene amplification in HCC showed no relationship with the clinical and pathological feature of the patients (all P > 0.05). Sequencing analysis showed 3 point mutations in the DcR3 gene mRNA of HCC in one case of positive amplification product.


CONCLUSIONS
DcR3 mRNA is overexpressed in HCC, but not in the normal tissues adjacent to the tumor. The expression of DcR3 gene is related to the size, clinical stage, infiltration, and metastasis of HCC. DcR3 gene amplification occurs in HCC and is correlated with the mRNA expression. Point mutation of the DcR3 gene exists in HCC.
Shen
Hong-wei
HW
Department of Surgery, Second Affiliated Hospital of Medical College, Zhejiang University, Hangzhou 310009, China.
Wu
Yu-lian
YL
Peng
Shu-you
SY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D017354:Point Mutation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000235:genetics; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004273:DNA, Neoplasm; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D053323:Receptors, Tumor Necrosis Factor, Member 6b; C505911:TNFRSF6B protein, human