Gene Expression Profiling of Intrahepatic Cholangiocarcinoma

Subrungruanga, Ittisak; Thawornkunob, Charin; Chawalitchewinkoon-Petmitrc, Porntip; Pairojkul, Chawalit; Wongkham, Sopit; Petmitrb, Songsak

doi:10.7314/apjcp.2013.14.1.557

Cited by 50 publications

(33 citation statements)

References 41 publications

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“…MACC1 mRNA expression was approximately 10 times higher in ICC and Klatskin tumors than in peritumorous normal liver tissue. Gene expression profiling in ICCs also showed elevated MACC1 expression levels . Whereas MACC1 expression in the Klatskin tumor cohort did not differ between UICC tumor stages, we found significantly higher MACC1 expression values in patients with a tumor size of pT3 and pT4, compared to pT1 and pT2.…”

Section: Discussionsupporting

confidence: 91%

Metastasis‐associated in colon cancer 1 is an independent prognostic biomarker for survival in klatskin tumor patients

et al. 2015

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Curative treatment of intrahepatic cholangiocarcinoma (ICC) and hilar cholangiocarcinoma (Klatskin tumors) is limited to surgical resection or orthotopic liver transplantation. However, not all patients benefit from a surgical approach and suffer from early tumor recurrence. Response to chemotherapy is generally poor and, until today, no targeted therapy could be established. Metastasis-associated in colon cancer 1 (MACC1) is a recently discovered regulator of the hepatocyte growth factor (HGF)/Met/mitogen-activated protein kinase pathway, which induces proliferation, migration, and invasion in cell culture, as well as metastasis in mice. MACC1 expression shows a significant correlation with Met expression in colon cancer tissue and is highly prognostic for occurrence of distant metastasis and survival in colon cancer patients. Thus, we aimed to measure the expression of MACC1, Met, and HGF messenger RNA in microdissected tumor tissue and corresponding normal liver tissue of 156 patients with Klatskin tumors (n 5 76) and ICC (n 5 80) using real-time quantitative reverse-transcriptase polymerase chain reaction. We used immunohistochemical staining to validate the results. MACC1 expression in tumor tissue of both tumor entities was significantly higher than in corresponding normal liver tissue (P < 0.001). Klatskin tumor patients with a history of tumor recurrence had significantly higher MACC1 expression than those without tumor recurrence (P 5 0.005). Uni-und multivariate survival analysis showed that Klatskin tumor patients with high MACC1 had a significantly shorter overall (OS) and disease-free survival (DFS; P 5 0.001 and P < 0.001, respectively). The multivariate analysis confirmed MACC1 to be an independent factor for overall survival in Klatskin tumor patients (hazard ratio: 2.777; 95% confidence interval: 1.389-5.555; P 5 0.004). Conclusion: Our study identified MACC1 as a highly prognostic biomarker for OS and DFS in Klatskin tumor patients. MACC1 expression could become an important diagnostic tool and might be a candidate for targeted therapy. (HEPATOLOGY 2015;62:841-850) C holangiocarcinomas (CCAs) are a rare disease, with an incidence rate <1 in 100,000 in Europe and in the United States. However, they are the second-most common primary tumor of the liver after hepatocellular carcinomas (HCCs) and account for approximately 20% of all deaths related to liver malignancies.1,2 CCAs occur at all sites of the biliary tree and can be divided in intrahepatic cholangiocarcinomas

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Section: Discussionsupporting

confidence: 91%

Metastasis‐associated in colon cancer 1 is an independent prognostic biomarker for survival in klatskin tumor patients

et al. 2015

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“…Various ITIH family members are down-regulated in a variety of human malignant tumors [25-27]. Paris et al .…”

Section: Discussionmentioning

confidence: 99%

Genome-wide in vivo RNAi screen identifies ITIH5 as a metastasis suppressor in pancreatic cancer

Sasaki

Kurahara

Young

et al. 2017

Clin Exp Metastasis

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The overwhelming majority of pancreatic ductal adenocarcinoma (PDAC) is not diagnosed until the cancer has metastasized, leading to an abysmal average life expectancy (3-6 months post-diagnosis). Earlier detection and more effective treatments have been hampered by inadequate understanding of the underlying molecular mechanisms controlling metastasis. We hypothesized that metastasis suppressors are involved in controlling metastasis in pancreatic cancer. Using an unbiased genome-wide shRNA screen, an shRNA library was transduced into the non-metastatic PDAC line S2-028 followed by intrasplenic injection. Resulting liver metastases were individually isolated from these mice. One liver metastatic nodule contained shRNA for ITIH5 (Inter-alpha-trypsin inhibitor heavy chain 5), suggesting that ITIH5 may act as a metastasis suppressor. Consistent with this notion, metastatic PDAC cell lines had significantly lower protein expression of ITIH5 compared to immortalized pancreatic ductal epithelial cells and non-/poorly-metastatic PDAC cell lines. By manipulating expression of ITIH5 in different PDAC cell lines (over-expression in metastatic, knockdown in non-metastatic) functional and selective regulation of metastasis was observed for ITIH5. Orthotopic tumor growth of PDAC cells was not blocked following orthotopic injection. In vitro ITIH5 over-expression inhibited motility and invasion. Immunohistochemical analysis of a human PDAC tissue microarray revealed that ITIH5 expression inversely correlated with both survival and invasion/metastasis. ITIH5 is, therefore, functionally validated as a PDAC metastasis suppressor and shows promise as a prognostic biomarker.

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“…This provided exon-level expression profiles, which might be useful for early diagnosis of CCA. 17 Shigehara et al demonstrated that some miRNAs (miR-9, miR-302c, miR199a-3p and miR-222) in human bile were more highly expressed in biliary tract cancer than in benign conditions, so miR-9 might be helpful in the diagnosis and clinical management of biliary tract cancer. 18 Markers for the precise prediction of the prognosis of CCA have been difficult to identify.…”

Section: Diagnosismentioning

confidence: 99%

A review of the clinical diagnosis and therapy of cholangiocarcinoma

2013

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Cholangiocarcinoma (CCA) is the second most common primary hepatic malignancy worldwide. The incidence of intrahepatic CCA is increasing, whereas that of extrahepatic CCA is decreasing. This review looks at the new advances that have been made in the management of CCA, based on a PubMed and Science Citation Index search of results from randomized controlled trials, reviews, and cohort, prospective and retrospective studies. Aggressive interventional approaches and new histopathological techniques have been developed to make a histological diagnosis in patients with high risk factors or suspected CCA. Resectability of the tumour can now be assessed using multiple radiological imaging studies; the main prognostic factor after surgery is a histologically negative resection margin. Biliary drainage and/or portal vein embolization may be performed before extended radical resection, or liver transplantation may be undertaken in combination with neoadjuvant chemotherapy or chemoradiotherapy. Though many advances have been made in the management of CCA, the standard modality of treatment has not yet been established. This review focuses on the clinical options for different stages of CCA.

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Gene Expression Profiling of Intrahepatic Cholangiocarcinoma

Cited by 50 publications

References 41 publications

Metastasis‐associated in colon cancer 1 is an independent prognostic biomarker for survival in klatskin tumor patients

Metastasis‐associated in colon cancer 1 is an independent prognostic biomarker for survival in klatskin tumor patients

Genome-wide in vivo RNAi screen identifies ITIH5 as a metastasis suppressor in pancreatic cancer

A review of the clinical diagnosis and therapy of cholangiocarcinoma

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