Clinical significance of CD13 and epithelial mesenchymal transition (EMT) markers in hepatocellular carcinoma

Chihiro Yamanaka, Hiroshi Wada, Hidetoshi Eguchi, Hisanori Hatano, Kunihito Gotoh, Takehiro Noda, Daisaku Yamada, Tadafumi Asaoka, Koichi Kawamoto, Hiroaki Nagano, Yuichiro Doki, Masaki Mori

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background & Aims: To improve prognosis in patients with hepatocellular carcinoma (HCC), the molecular mechanisms of tumor thrombus formation and metastasis must be clarified. The epithelial- mesenchymal transition (EMT) and cancer stem cells (CSCs) play crucial roles in tumor invasion and metastasis. This study aimed to reveal the clinical significance of the expression of the functional CSC marker, CD13, and investigate the correlation between CD13 expression and two EMT markers, E-cadherin and vimentin. Methods: We acquired clinical samples from 86 patients with HCC that underwent radical liver resections. We performed immunohistochemistry to evaluate CD13, E-cadherin and vimentin expression. We investigated the relationships among protein expression levels, clinicopathological factors and prognosis. Results: Based on CD13 expression, patients were categorized into CD13high (n = 30, 34.9%) and CD13low (n = 56, 65.1%) groups. The mean tumor size was significantly larger in the CD13high group than in the CD13low group (P = 0.049). Compared with the CD13low group, the CD13high group showed significantly earlier recurrences and shorter survival times. In the multivariate analysis, CD13high was an independent prognostic factor for overall survival (hazard ratio, 1.98; P = 0.044). The disease-free survival time was shorter in the vimentin-positive group than that in the vimentin-negative group (P = 0.014). In an analysis of the relationship between CD13 and EMT, there was no significant correlation between CD13 and EMT markers. Conclusions: Our findings suggested that CD13 enrichment was correlated with early recurrences, and poor prognosis in patients with HCC and that vimentin was associated with early recurrences. CD13 represents a potential therapeutic target for HCC, because CSC regulation and EMT suppression are essential in cancer therapy.

Original languageEnglish
Pages (from-to)52-60
Number of pages9
JournalJapanese journal of clinical oncology
Volume48
Issue number1
DOIs
Publication statusPublished - Jan 1 2018
Externally publishedYes

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Epithelial-Mesenchymal Transition
Vimentin
Hepatocellular Carcinoma
Neoplastic Stem Cells
Cadherins
Recurrence
Neoplasms
Neoplasm Metastasis
Survival
Mesenchymal Stromal Cells
Disease-Free Survival
Thrombosis
Multivariate Analysis
Immunohistochemistry
Liver
Therapeutics
Proteins

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Clinical significance of CD13 and epithelial mesenchymal transition (EMT) markers in hepatocellular carcinoma. / Yamanaka, Chihiro; Wada, Hiroshi; Eguchi, Hidetoshi; Hatano, Hisanori; Gotoh, Kunihito; Noda, Takehiro; Yamada, Daisaku; Asaoka, Tadafumi; Kawamoto, Koichi; Nagano, Hiroaki; Doki, Yuichiro; Mori, Masaki.

In: Japanese journal of clinical oncology, Vol. 48, No. 1, 01.01.2018, p. 52-60.

Research output: Contribution to journalArticle

Yamanaka, C, Wada, H, Eguchi, H, Hatano, H, Gotoh, K, Noda, T, Yamada, D, Asaoka, T, Kawamoto, K, Nagano, H, Doki, Y & Mori, M 2018, 'Clinical significance of CD13 and epithelial mesenchymal transition (EMT) markers in hepatocellular carcinoma', Japanese journal of clinical oncology, vol. 48, no. 1, pp. 52-60. https://doi.org/10.1093/jjco/hyx157
Yamanaka, Chihiro ; Wada, Hiroshi ; Eguchi, Hidetoshi ; Hatano, Hisanori ; Gotoh, Kunihito ; Noda, Takehiro ; Yamada, Daisaku ; Asaoka, Tadafumi ; Kawamoto, Koichi ; Nagano, Hiroaki ; Doki, Yuichiro ; Mori, Masaki. / Clinical significance of CD13 and epithelial mesenchymal transition (EMT) markers in hepatocellular carcinoma. In: Japanese journal of clinical oncology. 2018 ; Vol. 48, No. 1. pp. 52-60.
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AU - Wada, Hiroshi

AU - Eguchi, Hidetoshi

AU - Hatano, Hisanori

AU - Gotoh, Kunihito

AU - Noda, Takehiro

AU - Yamada, Daisaku

AU - Asaoka, Tadafumi

AU - Kawamoto, Koichi

AU - Nagano, Hiroaki

AU - Doki, Yuichiro

AU - Mori, Masaki

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AB - Background & Aims: To improve prognosis in patients with hepatocellular carcinoma (HCC), the molecular mechanisms of tumor thrombus formation and metastasis must be clarified. The epithelial- mesenchymal transition (EMT) and cancer stem cells (CSCs) play crucial roles in tumor invasion and metastasis. This study aimed to reveal the clinical significance of the expression of the functional CSC marker, CD13, and investigate the correlation between CD13 expression and two EMT markers, E-cadherin and vimentin. Methods: We acquired clinical samples from 86 patients with HCC that underwent radical liver resections. We performed immunohistochemistry to evaluate CD13, E-cadherin and vimentin expression. We investigated the relationships among protein expression levels, clinicopathological factors and prognosis. Results: Based on CD13 expression, patients were categorized into CD13high (n = 30, 34.9%) and CD13low (n = 56, 65.1%) groups. The mean tumor size was significantly larger in the CD13high group than in the CD13low group (P = 0.049). Compared with the CD13low group, the CD13high group showed significantly earlier recurrences and shorter survival times. In the multivariate analysis, CD13high was an independent prognostic factor for overall survival (hazard ratio, 1.98; P = 0.044). The disease-free survival time was shorter in the vimentin-positive group than that in the vimentin-negative group (P = 0.014). In an analysis of the relationship between CD13 and EMT, there was no significant correlation between CD13 and EMT markers. Conclusions: Our findings suggested that CD13 enrichment was correlated with early recurrences, and poor prognosis in patients with HCC and that vimentin was associated with early recurrences. CD13 represents a potential therapeutic target for HCC, because CSC regulation and EMT suppression are essential in cancer therapy.

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