The predictive value of chromosome 8p deletion for metastasis of hepatocellular carcinoma: a summary of works in 10 years

The predictive value of chromosome 8p deletion for metastasis of hepatocellular carcinoma: a summary of works in 10 years

Abstract

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 prediction 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 markers 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 metastatic 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 metastasis-related genes of HCC. Using ‘8p-specific’ microarrays, 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 circulating 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.

参考文献

1. Qin L X, Tang Z Y . Metastasis and recurrenceafter surgical resection of hepatocellular carcinoma: recent progressin clinical and related basic aspects. Crit Rev Cancer Ther, 2005, 1(1): 71–80. doi:10.2174/1573394052952492
2. Qin L X, Tang Z Y . Recent progress in predictivebiomarkers for metastatic recurrence of human hepatocellular carcinoma:a review of the literature. J Cancer ResClin Oncol, 2004, 130(9): 497–513. doi:10.1007/s00432‐004‐0572‐9
3. Qin L X, Tang Z Y . The prognostic molecularmarkers in hepatocellular carcinoma. WorldJ Gastroenterol, 2002, 8(3): 385–392
4. Qin L X, Tang Z Y . The prognostic significanceof clinical and pathological features in hepatocellular carcinoma. World J Gastroenterol, 2002, 8(2): 193–199
5. Qin L X . Chromosomal aberrations related to metastasis of human solid tumors. World J Gastroenterol, 2002, 8(5): 769–776
6. Qin L X, Tang Z Y, Sham J S, Ma Z C, Ye S L, Zhou X D, Wu Z Q, Trent J M, Guan X Y . The associationof chromosome 8p deletion and tumor metastasis in human hepatocellularcarcinoma. Cancer Res, 1999, 59(22): 5662–5665
7. Qin L X, Tang Z Y, Ye S L, Liu Y K, Ma Z C, Zhou X D, Wu Z Q, Lin Z Y, Sun F X, Tian J, Guan X Y, Park S D, Zhuang Z P . Chromosome 8p deletion is also associated with metastasisof human hepatocellular carcinoma when comparison was made betweenhigh and low metastatic models. J CancerRes Clin Oncol, 2001, 127(8): 482–488. doi:10.1007/s004320100236
8. Yang J, Qin L X, Ye S L, Liu Y K, Li Y, Gao D M, Chen J, Tang Z Y . The aberrations of chromosome 8 in two hepatocellular carcinoma cellclones with the same genetic background and different metastatic potential. J Cancer Res Clin Oncol, 2003, 129(5): 303–308
9. Yang J, Qin L X, Li Y, Ye S L, Liu Y K, Gao D M, Chen J, Tang Z Y . Molecular cytogenetic characteristics of the human hepatocellularcarcinoma cell line HCCLM3 with high metastatic potential: comparativegenomic hybridization and multiplex fluorescence in situ hybridization. Cancer Genet Cytogenet, 2005, 158(2): 180–183. doi:10.1016/j.cancergencyto.2004.05.010
10. Zhang L H, Qin L X, Ma Z C, Ye S L, Liu Y K, Ye Q H, Wu X, Huang W, Tang Z Y . Allelic imbalanceregions on chromosomes 8p, 17p and 19p related to metastasis of hepatocellularcarcinoma: comparison between matched primary and metastatic lesionsin 22 patients by genome-wide microsatellite analysis. J Cancer Res Clin Oncol, 2003, 129(5): 279–286
11. Wu X, Jia H L, Wang Y F, Ren N, Ye Q H, Sun H C, Wang L, Liu Y K, Tang Z Y, Qin L X . HTPAP gene on chromosome 8p is a candidatemetastasis suppressor for human hepatocellular carcinoma. Oncogene, 2006, 25(12): 1832–1840. doi:10.1038/sj.onc.1209191
12. Lei K F, Wang Y F, Zhu X Q, Lu P C, Sun B S, Jia H L, Ren N, Ye Q H, Sun H C, Wang L, Tang Z Y, Qin L X . Identification of MSRA gene on chromosome 8p as a candidatemetastasis suppressor for human hepatitis B virus-positive hepatocellularcarcinoma. BMC Cancer, 2007, 7: 172. doi: 10.1186/1471‐2407‐7‐172
13. Pang J Z, Qin L X, Ren N, Ye Q H, Jia W D, Sun B S, Lin G L, Liu D Y, Liu Y K, Tang Z Y . Loss of heterozygosity at D8S298 is apredictor for long-term survival of patients with TNM stage I of hepatocellularcarcinoma. Clin Cancer Res, 2007, 13(24): 7363–7369. doi:10.1158/1078‐0432.CCR‐07‐0593
14. Ren N, Qin L X, Tu H, Liu Y K, Zhang B H, Tang Z Y . The prognostic value of circulating plasma DNA level and its allelicimbalance on chromosome 8p in patients with hepatocellular carcinoma. J Cancer Res Clin Oncol, 2006, 132(6): 399–407. doi:10.1007/s00432‐005‐0049‐5