摘要
Hepatocellular carcinoma(HCC)represents an extremely poor prognostic cancer,which is mainly due to the high frequency of metastasis/recurrence after surgical operation.Exploring the molecular mechanisms involved in HCC metastasis could be helpful in the pre-diction and early diagnosis of HCC recurrence and could also provide new therapeutic targets for HCC metastasis.In the recent decade,we analyzed the genomic aberrations of the clinical specimens,as well as the metastatic models and cell lines of human HCC to identify the genetic mar-kers related to HCC metastasis and to verify their clinical values in the prediction and control of metastasis of HCC.Using the comparative genomic hybridization(CGH)technique,we compared the differences of chromosomal aberrations between primary HCC tumors and their matched metastatic lesions,and found that chromosome 8p deletions might contribute to HCC metastasis.This novel finding was further confirmed by comparison between nude mice models of HCC with different meta-static potentials.By the more sensitive genome-wide microsatellite analysis,8p deletion was defined to 8p23.3 and 8p11.2,which are two likely regions harboring meta-stasis-related genes of HCC.Using‘8p-specific’microar-rays,two novel metastatic suppressors(HTPAP and MRSA)were identified,and were proven to suppress in vitro invasion and in vivo metastasis of HCC.Clinical studies indicate that 8p deletion detected in HCC or cir-culating plasma DNA of patients is a useful predictor for metastatic recurrence and prognosis,even for patients with early stage HCC.These novel findings are regarded as important advances in the study of the molecular mechanisms of HCC metastasis,which provide not only a holistic view on the molecular cytogenetic bases of HCC metastasis,but also candidate regions for further study to identify metastatic suppressor genes.
基金
supported in part by Grants from National Natural Science Foundation for Distinguished Young Scholars(No.30325041)
the National High Technology Research and Development Program of China(863 Program)(No.2006AA02Z473)
the Shanghai Science and Technology Developing Program(No.03DZ14024)
the Foundation for Outstanding Scholars in New Era of the Ministry of Education of China.
