促肝细胞再生磷酸酶-3基因在结直肠癌组织中的表达及其临床意义

目的检测促肝细胞再生磷酸酶-3(PRL-3)mRNA在结直肠癌(CRC)中的表达,探讨其与CRC发生发展以及侵袭转移的关系。方法半定量PCR测定46例CRC组织及其对应正常黏膜、6例结直肠腺瘤(CRA)及其对应正常黏膜以及18例淋巴结和肝转移灶中PRL-3mRNA相对表达水平,并分析其表达水平与临床病理学指标的关系。单链多态性分析法(PCR-SSCP)检测基因突变情况。结果46例CRC中PRL-3基因表达量较相应正常黏膜组织高,差异有统计学意义(1.6±0.7比0.4±0.1,P<0.01);6例结直肠腺瘤组织与对应的正常黏膜中PRL-3mRNA表达量差异无统计学意义(0.6±0.3比0.5±0.2,P>0.05);12例淋巴结转移灶和6例肝转移灶PRL-3基因表达量分别为2.1±0.8和3.3±1.0,显著高于原发癌肿、正常黏膜、阴性淋巴结组织中的表达(P<0.01)。PRL-3基因表达水平与CRCDukes分期、浸润深度、淋巴结和远处转移有关(P<0.05),与性别、肿瘤大小、分化程度无关(P>0.05)。PCR-SSCP分析发现,6例肝转移灶中有1例出现异常泳动条带。结论PRL-3基因在CRC的发生发展和侵袭转移中起重要作用,其作用可能是通过基因表达上调和基因突变共同实现的。

Expression of phosphatase of regenerating liver- 3 mRNA and its clinical implications in human colorectal carcinoma

OBJECTIVE: To investigate the expression of phosphatase of regenerating liver-3 (PRL- 3) mRNA and evaluate its relationship with tumor invasion and metastasis in human colorectal carcinoma. METHODS: The expression level of PRL-3 mRNA was examined semi-quantitatively in surgically resected tumor specimens, paired paratumor normal tissues from 46 CRC patients, metastatic lymph nodes and liver metastases from 18 cases with metastasis,adenoma tissues from 6 patients with colorectal adenoma (CRA). In addition,the mutation of PRL-3 gene was examined by PCR-SSCP. RESULTS: The PRL-3 mRNA level was increased in primary CRC tissues as compared with paired paratumor normal tissues (1.6+/- 0.7 vs. 0.4+/- 0.1, P< 0.01), while no significant difference of its expression was found between CRA tissues and their adjacent normal mucosae (P> 0.05). However,the PRL-3 mRNA levels of liver metastases (2.1+/- 0.8) in 12 cases and metastatic lymph nodes (3.3+/- 1.0) in 6 cases were significantly higher compared with the matched primary lesions, normal tissues and negative-lymph nodes (P< 0.01). There was significant relation of the expression of PRL-3 mRNA with the clinicopathological features including Dukes stage, invasion depth and metastasis (P< 0.05), but no relation with sex,tumor size,degree of differentiation was found (P> 0.05). Abnormal electroresis band was found in 1 of 6 cases with liver metastasis by PCR-SSCP analysis. CONCLUSION: PRL-3 gene plays an important role in tumor invasion and metastasis and may associated with carcinogenesis and development of CRC. There might exist some unknown mechanisms of overexpression and mutation of PRL-3 gene in CRC.