CD133 expression is a potential prognostic indicator in intrahepatic cholangiocarcinoma

Shimada, Mitsuo; Sugimoto, Koji; Iwahashi, Shuichi; Utsunomiya, Tohru; Morine, Yuji; Imura, Satoru; Ikemoto, Tetsuya

doi:10.1007/s00535-010-0235-3

Cited by 62 publications

(61 citation statements)

References 27 publications

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“…However, few new markers associated with prognosis or malignant behavior of ICC has been determined (Oishi et al 2012;Shimada et al 2010). In this study we studied Nogo-B, which has recently been identified as a potential marker of hepatic fibrosis (Zhang et al 2011;Gao et al 2013;Tashiro et al 2013;Men et al 2015) and as a potential enhancer of bile duct proliferation (Zhang Each survival rate is shown as % value, based on our analytical software.…”

Section: Macroscopic Findingmentioning

confidence: 99%

Down-Regulation of Nogo-B Expression as a Newly Identified Feature of Intrahepatic Cholangiocarcinoma

Nanashima

Hatachi

Tominaga

et al. 2016

Tohoku J. Exp. Med.

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Nogo-B, located in the endoplasmic reticulum, is an isoform belonging to the reticulon protein family, which is expressed specifically in cholangiocytes and non-parenchymal cells in the liver. Nogo-B expression is down-regulated with the progression of liver fibrosis, but its distinct function in liver malignancies has not been fully clarified. We have hypothesized that Nogo-B expression may be altered in intrahepatic cholangiocarcinoma (ICC), a relatively rare type of primary liver cancer with highly malignant behavior. The present study aimed to investigate the relationship between Nogo-B expression, assessed by immunohistochemical staining, and clinicopathological factors and prognosis in 34 ICC patients. Positive expression was observed in 19 (56%) of 34 ICC specimens: 6 patients (18%) with positivity levels of 1+ (positive cells in 10-50% of cancer cells) and 13 patients (38%) with 2+ (positive cells over 50%). Importantly, the remaining 15 patients (44%) were categorized as negative expression (Nogo-B-positive cells, less than 10%). Conversely, the mass-forming type of ICC tended to express Nogo-B with the degree of 2+ positivity, compared to the periductal infiltration type (p = 0.064), and the mass-forming type showed a better 5-year survival rate (66% vs. 5%) after hepatectomy (p < 0.05). However, the degree of positivity was not associated with tumor relapse rate, disease-free and overall survival, although each of the periductal infiltration type, intrahepatic metastasis, larger tumor size, and lower microvessel counts was associated with lower survival rates. We propose that Nogo-B expression is down-regulated in ICC, the implication of which, however, remains to be investigated.

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Section: Macroscopic Findingmentioning

confidence: 99%

Down-Regulation of Nogo-B Expression as a Newly Identified Feature of Intrahepatic Cholangiocarcinoma

Nanashima

Hatachi

Tominaga

et al. 2016

Tohoku J. Exp. Med.

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“…[19]. Recent studies revealed that CD133 is an important cancer stem cell marker of solid tumors including cholangiocarcinoma [20][21][22] and liver tumors [4,23]. In an in-vitro study using a cholangiocarcinoma cell line, CD133-positive cells had higher invasiveness compared with CD133-negative cells [24].…”

Section: Molecular Cholangiocarcinoma Stem Cell Markersmentioning

confidence: 99%

“…Shimada et al [22] analyzed CD133 expression in 29 patients with intrahepatic cholangiocarcinoma. In their study, the 5-year survival rate in the CD133-positive group (8 %) was worse than that in the CD133-negative group (57 %), and the incidence of intrahepatic metastasis was higher in the CD133-positive group.…”

Section: Hepatic Stem Cellmentioning

confidence: 99%

Recent advances in cancer stem cell research for cholangiocarcinoma

Kokuryo

Yokoyama

Nagino

2012

J Hepato Biliary Pancreat

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Cancer stem cells have been identified as cells with the capacity to self‐renew and differentiate into multiple lineages of human malignancies. Cholangiocarcinoma is one of the most difficult intra‐abdominal malignancies that can be treated using a surgical approach. Chemotherapy in addition to surgery is necessary to improve patient survival. However, its clinical benefit is limited, and, to date, no other effective anticancer drug is available for this disease. Several reports have shown the existence of cholangiocarcinoma stem cells. Cell surface antigens such as CD133, CD24, EpCAM, CD44, and others have been used to isolate cholangiocarcinoma stem cells. In general, enhanced expression of these markers in resected specimens of cholangiocarcinoma was associated with malignant potential. Distinct and specific pathways are expected to be present in cancer stem cells compared to other cancer cells that have no stem cell properties. To date, reports showing possible signaling pathways in cholangiocarcinoma stem cells are limited. More research is anticipated. Targeting therapies for surface molecular markers or specific signaling pathways of cholangiocarcinoma stem cells may be important in order to change the clinical outcome of patients with this disease. However, no clinical trial has been performed so far. This review will focus on the markers and signaling pathways used to define cholangiocarcinoma stem cells. A novel therapeutic approach of targeting cholangiocarcinoma stem cells will also be discussed.

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“…CD133-positive cells showed higher invasiveness compared with CD133-negative cells. Shimada et al [75] analyzed CD133 expression in 29 patients with intrahepatic CCA and found that the 5-year survival rate in the CD133-positive group (8%) was worse than that in the CD133-negative group [76]. However, Fan et al [77] reported contrasting results, in which CD133 expression was correlated with a higher tumor diferentiation status in 54 consecutively analyzed CCA specimens.…”

Section: Csc Markers In Ccamentioning

confidence: 99%

Cancer Stem Cells and Aldehyde Dehydrogenase 1 in Liver Cancers

Tomita¹,

Kanayama²,

Niwa³

et al. 2017

Updates in Liver Cancer

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The cancer stem cell (CSC) theory posits that a small population of cells with stem celllike features is responsible for tumor growth, resistance, and recurrence in many malignancies. This theory could be a useful paradigm for designing innovative targeted drug therapies. Liver cancer is the ifth most common cancer worldwide, with hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) as the predominant forms. Hepatic stem/progenitor cells are believed to be the origin of HCCs and CCAs; however, this remains a controversial topic. Aldehyde dehydrogenase (ALDH) is the main enzymatic system responsible for the clearance of acetaldehyde from the hepatocytes in the liver tissue. Therefore, ALDH1 has been suggested to be a potential, biological and CSC marker in liver cancers. We here provide an overview of the current state of knowledge of CSCs in liver and the role of ALDH1 in the development and progression of liver cancers and discuss its potential value as a prognostic and diagnostic biomarker.

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CD133 expression is a potential prognostic indicator in intrahepatic cholangiocarcinoma

Abstract: CD133 expression tended to be related to higher incidences of intrahepatic metastasis and positive expression of hypoxia-inducible factor-1alpha; furthermore, it was independently related to worse prognosis. Therefore, the CD133 expression is a potential prognostic indicator in IHCC.

Cited by 62 publications

References 27 publications

Down-Regulation of Nogo-B Expression as a Newly Identified Feature of Intrahepatic Cholangiocarcinoma

Down-Regulation of Nogo-B Expression as a Newly Identified Feature of Intrahepatic Cholangiocarcinoma

Recent advances in cancer stem cell research for cholangiocarcinoma

Cancer Stem Cells and Aldehyde Dehydrogenase 1 in Liver Cancers

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