Project description:To demonstrate CD133+CD44+ and CD133+CD44- subpopulations of hepatocellular carcinoma as distinct subgroups, we have employed whole genome microarray expression profiling as a discovery platform to reveal the gene profiles of different subgroups and identify genes responsible for the enhanced metastatic potentials of CD133+CD44+ tumor cells. CD133+CD44+ and CD133+CD44- tumor cells were isolated from three human metastatic hepatocellular carcinoma specimens. A 76-gene consensus signature was identified that distinguished between CD133+CD44+ and CD133+CD44- subgroups. CD133+CD44+ and CD133+CD44- subgroups from different patients were well clustered as two distinct classes according to this signature, and many genes in this signature were reported involved in tumor metastasis. Expression of four genes (CCL4, DKK3, CCR5 and MMP12) from this signature was confirmed in another three metastatic HCC specimens by real-time PCR. CD133+CD44+ and CD133+CD44- subpopulations of hepatocellular carcinoma were isolated from three metastatic hepatocellular carcinoma specimens by flow cytometry. A total of 30K to 50K cells for each subgroup was obtained for each microarray.
Project description:Aberrant expression of LncRNAs might be responsible for the HCC invasion and metastasis. we employed the LncRNAs microarray technology to study the LncRNAs expression profiles at genome-wide in hepatocellular carcinoma (HCC)tissue samples with early recurrence (less than 1 year, with invasion and metastasis out of liver) and late recurrence (longer than 2 years, without invasion and metastasis out of liver), which had different recurrent/metastatic potentials, by using normal liver tissue as control to screen the dysregulated LncRNAs which are potentially involved in the recurrence, invasion and metastasis process of HCC
Project description:To reduce cancer mortality, understanding of mechanisms of cancer metastasis is crucial. We have established 6 rat hepatocellular carcinoma (HCC) cell lines, which exhibit differing metastatic potential to the lung after inoculation into the tail veins of nude mice. Micorarray analysis of 4 kinds of HCC cells and rat normal liver tissue was performed to find a potent molecular target for prevention of cancer metastasis. By the microarray analysis, mRNA expression was compared among two low-metastatic rat HCC cell lines (C5F and C6) and two high-metastatic rat HCC cell lines (N1 and L2) as well as non-treated rat liver tissue (as a reference sample).
Project description:Hepatectomy generally offers the best chance of long-term survival for patients with hepatocellular carcinoma (HCC). Many studies have shown that hepatectomy accelerates tumor metastasis, but the mechanism remains unclear. In this study, palliative hepatectomy was performed in an orthotopic nude mice model of HCC (MHCC97H) with high metastatic potential. Using Human Tumor Metastasis Microarray, we screened the metastasis-related genes in tumor tissues following palliative resection, and found that Metastasis suppressor 1 (MTSS1) located in the central position of gene function net of residual HCC; MTSS1 was up-regulated in residual tumor after palliative resection. Further studies found that MTSS1 enhanced the metastasis of residual HCC. In hepatitis B-related HCC patients undergone palliative hepatectomy, those with higher MTSS1 mRNA expression accompanied by the activation of matrix metalloproteinase 2 (MMP2) in residual HCC, had earlier residual HCC detection after hepatectomy and poorer survival when compared to those with lower MTSS1 level. In different cell lines, the levels of MTSS1 mRNA increased in parallel with metastatic potential. MTSS1 down regulation via siRNA decreased MMP2 activity, reduced invasive potentials of HCC by 28.9% in vitro, and averted the deteriorated lung metastatic extent in vivo. In conclusion, the poor prognosis of hepatitis B-related HCC patients following palliative hepatectomy associates with elevated MTSS1 mRNA expression; therefore, MTSS1 may provide a new research field for HCC diagnosis and treatment. Eighteen nude mice bearing HCC xenografts were randomized into three groups 14 days after orthotopic implantation: palliative resection group (mice received partial HCC resection with preservation of 2 mm tumor pedicles), sham operation group (mice only undergone an exposure of liver but without resection), and blank control group (mice without further surgical intervention). All mice were sacrificed by cervical dislocation 14 days following palliative resection based on pre-experimental results. The first time surgically removed HCC tissues were named tumor tissues T1; the second time surgically removed HCC tissues from sham operation group were named tumor tissues T2; Tissues from blank control group were named tumor tissues T3; Tissues from palliative resection group were named tumor tissues T4 that was residual HCC. Randomly selected 5 tumor specimens from each group were used for the screen of genes related to metastasis by microarray techniques.
Project description:To demonstrate CD133+CD44+ and CD133+CD44- subpopulations of hepatocellular carcinoma as distinct subgroups, we have employed whole genome microarray expression profiling as a discovery platform to reveal the gene profiles of different subgroups and identify genes responsible for the enhanced metastatic potentials of CD133+CD44+ tumor cells. CD133+CD44+ and CD133+CD44- tumor cells were isolated from three human metastatic hepatocellular carcinoma specimens. A 76-gene consensus signature was identified that distinguished between CD133+CD44+ and CD133+CD44- subgroups. CD133+CD44+ and CD133+CD44- subgroups from different patients were well clustered as two distinct classes according to this signature, and many genes in this signature were reported involved in tumor metastasis. Expression of four genes (CCL4, DKK3, CCR5 and MMP12) from this signature was confirmed in another three metastatic HCC specimens by real-time PCR.
Project description:HCC cell lines with different metastatic potential (HepG2, Huh7, MHCC97 and PVTT cells) were treated with TGFbeta1 for 8 h We used microarrays to discover the long non-coding RNAs (lncRNAs) expression underlying Hepatocellular carcinoma (HCC) TGFbeta1 treated and non-treated control cells to identify distinct lncRNAs during this process.