Genome-wide analysis of gene expression in human intrahepatic cholangiocarcinoma

Abstract

Intrahepatic cholangiocarcinoma is a neoplasm arising in the liver, and its incidence is increasing in Japan as well as in Western countries. Prognosis of patients with this type of tumor remains unsatisfactory because no effective chemotherapeutic drugs are available, we have no sensitive tumor markers to detect this tumor in its early stage, and it is difficult to identify a high-risk group for the disease. To clarify the molecular mechanism of tumorigenesis and identify molecular targets for diagnosis and treatment, we analyzed global gene-expression profiles of 25 intrahepatic cholangiocarcinomas using tumor cell populations purified by laser microbeam microdissection and a cDNA microarray containing 27,648 genes. We identified 52 genes that were commonly upregulated and 421 that were downregulated in intrahepatic cholangiocarcinomas compared with noncancerous biliary epithelial cells. From the 52 upregulated genes, we selected P-cadherin and survivin for further investigation and corroborated enhanced expression of their products in cancer tissues by immunohistochemical staining. Furthermore, comparison between tumors with lymph node metastasis and those without metastasis identified 30 genes that were associated with lymph node involvement. In conclusion, these data should be helpful for a better understanding of the tumorigenesis of intrahepatic cholangiocarcinoma and should contribute to the development of diagnostic and therapeutic strategies for this type of tumor.

Transgenic expression of the forkhead box M1 transcription factor induces formation of lung tumors

“…Consistent with the important role of Foxm1 in cell cycle progression, elevated Foxm1 levels have been found in a variety of tumor cell lines (Korver et al, 1997;Ye et al, 1997) as well as numerous types of human tumors (Teh et al, 2002;van den Boom et al, 2003;Lee et al, 2004;Obama et al, 2005;Wonsey and Follettie, 2005;Kalin et al, 2006). Our recent studies demonstrated that Foxm1 protein is abundantly expressed in highly proliferative human NSCLC as well as in mouse lung tumors induced by urethane (Kim et al, 2006).…”

“…Consistent with an important role of Foxm1 in cell cycle progression, increased expression of Foxm1 was found in human lung adenocarcinomas and squamous cell carcinomas (Kim et al, 2006), prostate adenocarcinomas , basal cell carcinomas (Teh et al, 2002), intrahepatic cholangiocarcinomas (Obama et al, 2005), anaplastic astrocytomas and glioblastomas (van den Boom et al, 2003), infiltrating ductal breast carcinomas (Wonsey and Follettie, 2005), as well as in many other solid tumors (Pilarsky et al, 2004). Foxm1 is also overexpressed in hepatocellular carcinomas from patients who respond poorly to treatment (Lee et al, 2004).…”

Gene Expression Profiling of Intrahepatic Cholangiocarcinoma

“…Gene expression profile of 25 Japanese ICC patients (10 mass-forming, 2 periductal infiltrating, 11 mixed subtypes (mass-forming and periductal infiltrating) and 2 unknown subtype), using an in-house cDNA microarray demonstrated 52 up-regulated and 421 down-regulated genes (Obama et al, 2005). A comparison of global gene expression profiles of 20 Opisthochis viverrini-associated Thai ICC patients [10 mass-forming type and 10 mixed subtype (mass-forming and intraductal growth type)], with 20 Japanese ICC patients [8 mass-forming, 2 intraductal growth type and 10 mixed subtypes (mass-forming and intraductal growth type)], using an in-house cDNA microarray, indicated 77 up-regulated genes and 325 down-regulated genes in common (Jinawath et al, 2006).…”

“…Although various genetic markers in different types cancers and their sub-classification have been widely exploited using this technique (Chee et al, 1996;Golub et al, 1999;Kim et al, 2004), there are only two publications using in-house cDNA microarrays to produce a comprehensive analysis of gene expression profiles in ICC mass forming subtype (Obama et al, 2005;Jinawath ,et al, 2006) and another for gene expression profile in billiary tract cancer (gallbladder carcinoma, ICC and distal bile duct carcinoma) using Affymetrix GeneChip U133A expression array (Hansel et al, 2003).…”

CDC20, a potential cancer therapeutic target, is negatively regulated by p53

“…After amplified RNAs (aRNAs) were labeled with Cy3 or Cy5, respectively, we carried out hybridization between labeled aRNAs and cDNA microarray slides containing 36 864 spots and detected the signals. Expression of CDC20 in various cancer tissues and their corresponding normal tissues were examined by using data sets that were analysed previously (Ono et al, 2000;Kitahara et al, 2001;Okabe et al, 2001;Hasegawa et al, 2002;Kaneta et al, 2002;Kitahara et al, 2002;Nagayama et al, 2002;Okutsu et al, 2002;Kikuchi et al, 2003;Okada et al, 2003;Ashida et al, 2004;Jinawath et al, 2004;Nakamura et al, 2004;Nishidate et al, 2004;Ochi et al, 2004;Obama et al, 2005;Takata et al, 2005;Hirota et al, 2006;Taniwaki et al, 2006;Yamabuki et al, 2006). To select genes that were suppressed by p53 and upregulated in various cancer tissues, the following two criteria were used: (1) genes whose expression were more than threefold decreased by Ad-p53 and (2) genes whose expression were more than threefold increased in various cancer tissues compared with its corresponding normal tissues.…”