BACKGROUND: Recurrent chromosome 20q gain is implicated in progressive cancer behaviors and has been associated with clinical outcomes in multiple types of cancer; however, its prognostic significance in hepatocellular carcinoma (HCC) and the involved genes remain unclear. METHODS: Array comparative genomic hybridization and expression arrays were used to detect copy number alterations (CNAs) and expression levels, respectively. The associations between CNAs in 20q and outcomes were analyzed on 66 patients, for which the follow-up period was 2.6-73.3 months. One hundred seventeen tumors were further investigated to identify target genes in the potentially outcome-related CNAs. RESULTS: Regional or whole 20q gain was detected in 24 (36.4%) of the 66 HCC cases. The most recurrent gains were 20q11.21-12, 20q12-13.12, 20q13.12-13.33 and 20q13.33. Of the CNAs, 20q13.12-13.33 gain was significantly associated with reduced extrohepatic metastasis-free and overall survival, as well as with elevated postoperative AFP level, tumor vascular invasion and advanced tumor stage. Multivariate Cox analysis identified 20q13.12-13.33 gain as an independent prognostic marker for metastasis (HR 3.73, 95% CI 1.08-12.87) and death (HR 3.00, 95% CI 1.26-7.13). A panel of 19 genes in 20q13.12-13.33 was significantly overexpressed in HCCs with gain compared to HCCs without. High expression (greater than median) for 5 of the 19 genes, DDX27, B4GALT5, RNF114, ZFP64 and PFDN4, correlated significantly with vascular invasion, and high RNF114 expression also with advanced tumor stage. CONCLUSIONS: Gain at 20q13.12-13.33 is a prognostic marker of metastasis and death, and DDX27, B4GALT5, RNF114, ZFP64, and PFDN4 are probable target genes which may be involved together in the unfavorable outcomes of HCC patients.
BACKGROUND: Recurrent chromosome 20q gain is implicated in progressive cancer behaviors and has been associated with clinical outcomes in multiple types of cancer; however, its prognostic significance in hepatocellular carcinoma (HCC) and the involved genes remain unclear. METHODS: Array comparative genomic hybridization and expression arrays were used to detect copy number alterations (CNAs) and expression levels, respectively. The associations between CNAs in 20q and outcomes were analyzed on 66 patients, for which the follow-up period was 2.6-73.3 months. One hundred seventeen tumors were further investigated to identify target genes in the potentially outcome-related CNAs. RESULTS: Regional or whole 20q gain was detected in 24 (36.4%) of the 66 HCC cases. The most recurrent gains were 20q11.21-12, 20q12-13.12, 20q13.12-13.33 and 20q13.33. Of the CNAs, 20q13.12-13.33 gain was significantly associated with reduced extrohepatic metastasis-free and overall survival, as well as with elevated postoperative AFP level, tumor vascular invasion and advanced tumor stage. Multivariate Cox analysis identified 20q13.12-13.33 gain as an independent prognostic marker for metastasis (HR 3.73, 95% CI 1.08-12.87) and death (HR 3.00, 95% CI 1.26-7.13). A panel of 19 genes in 20q13.12-13.33 was significantly overexpressed in HCCs with gain compared to HCCs without. High expression (greater than median) for 5 of the 19 genes, DDX27, B4GALT5, RNF114, ZFP64 and PFDN4, correlated significantly with vascular invasion, and high RNF114 expression also with advanced tumor stage. CONCLUSIONS: Gain at 20q13.12-13.33 is a prognostic marker of metastasis and death, and DDX27, B4GALT5, RNF114, ZFP64, and PFDN4 are probable target genes which may be involved together in the unfavorable outcomes of HCC patients.
Authors: Y Midorikawa; S Yamamoto; S Ishikawa; N Kamimura; H Igarashi; H Sugimura; M Makuuchi; H Aburatani Journal: Oncogene Date: 2006-06-19 Impact factor: 9.867
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