Copy Number Aberrations of Multiple Genes Identified as Prognostic Markers for Extrahepatic Metastasis-free Survival of Patients with Hepatocellular Carcinoma.

Extrahepatic metastasis confers unfavorable patient prognosis in patients with hepatocellular carcinoma (HCC), however, reliable markers allowing prediction of extrahepatic metastasis at the time of initial diagnosis are still lacking. This study was to identify gene-level copy number aberrations (CNAs) related to extrahepatic metastasis-free survival of HCC patients, and further examine the associations between CNAs and gene expression. Array comparative genomic hybridization (aCGH) and expression array were used to analyze gene CNAs and expression levels, respectively. The associations between CNAs of a panel of 20 genes and extrahepatic metastasis-free survival were analyzed in 66 patients with follow-up period of 1.6-90.5 months. The gene expression levels between HCCs with and without gene CNA were compared in 109 patients with HCC. We observed that gains at MDM4 and BCL2L1, and losses at APC and FBXW7 were independent prognostic markers for extrahepatic metastasis-free survival of HCC patients. Integration analysis of aCGH and expression data showed that MDM4 and BCL2L1 were significantly upregulated in HCCs with gene gain, while APC and FBXW7 were significantly downregulated in HCCs with gene loss. We concluded that gene gains at MDM4 and BCL2L1, and losses at APC and FBXW7, with concordant expression changes, were associated with extrahepatic metastasis-free survival of HCC patients and have potential to act as novel prognostic markers.

Multiple genes identified as targets for 20q13.12-13.33 gain contributing to unfavorable clinical outcomes in patients with hepatocellular carcinoma.

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.

[Phytoplankton distribution and variation in the Yangtze River Estuary and its adjacent sea].

Two cruises were carried out in the Yangtze River Estuary and its adjacent sea (29 degrees 30' - 32 degrees 00'N, west of 123 degrees E) in July (summer) and November (autumn), 2005. A total of 345 phytoplankton species, including 43 species causing red tide, were identified. Skeletonema costatum was the dominant species. The average cell abundance was lower in July (5.48 x 10(4) cells L(-1)) than in November (2.70 x 10(5) cells L-(-1)), but the average chlorophyll a concentration was higher in July (2.34 mg x m(-3)) than in November (1.32 mg x m(-3)). The average diversity index (H) was higher in July (1.51) than in November (0.86), as was average evenness (J) (0.59 and 0.34, respectively). Spatial distribution of phytoplankton featured distinct regionality, and the seasonal variation was controlled by factors such as water source, monsoon, nutrient, suspended matter, etc., and the diurnal variation mainly correlated with tide and stratification. At the same time, an evaluation of long-term monitoring data (1996 - 2005) showed that phytoplankton community structure had been changed. Long-term unbalance of N/P ratio caused dinoflagellates to increasingly dominate the phytoplankton population, and led to an increasing frequency of red tide caused by dinoflagellates. Controlling nutrient ratios is more important than just controlling terrigenous contamination input in improving sea area environmental status.