Lysyl oxidase induces epithelial‐mesenchymal transition and predicts intrahepatic metastasis of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) has high recurrence rates even after curative hepatectomy. Drug therapy for recurrence of HCC is still limited; therefore, identifying new therapeutic targets is urgently needed. We searched for genes that would predict HCC recurrence from intrahepatic metastasis in an...

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Bibliographic Details
Published in:Cancer science 2019-06, Vol.110 (6), p.2033-2043
Main Authors: Umezaki, Naoki, Nakagawa, Shigeki, Yamashita, Yo‐ichi, Kitano, Yuki, Arima, Kota, Miyata, Tatsunori, Hiyoshi, Yukiharu, Okabe, Hirohisa, Nitta, Hidetoshi, Hayashi, Hiromitsu, Imai, Katsunori, Chikamoto, Akira, Baba, Hideo
Format: Article
Language:English
Subjects:
Aged
Antigens
Cancer therapies
Carcinoma, Hepatocellular - enzymology
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - pathology
Cell Line, Tumor
Cell Movement - genetics
DNA microarrays
Drug therapy
early recurrence
Epithelial-Mesenchymal Transition - genetics
epithelial‐mesenchymal transition
Female
Gene Expression Regulation, Neoplastic
Hepatectomy
Hepatitis
Hepatocellular carcinoma
Humans
Hypoxia
Hypoxia-Inducible Factor 1, alpha Subunit - genetics
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
intrahepatic metastasis
Liver cancer
Liver diseases
Liver Neoplasms - enzymology
Liver Neoplasms - genetics
Liver Neoplasms - pathology
Lysyl oxidase
Male
Medical imaging
Medical prognosis
Mesenchyme
Metastases
Metastasis
Middle Aged
Migration
Multivariate analysis
Neoplasm Metastasis
Neoplasm Recurrence, Local
NMR
Nuclear magnetic resonance
Original
Patients
Prognosis
Protein-Lysine 6-Oxidase - genetics
Protein-Lysine 6-Oxidase - metabolism
Risk factors
Survival
Therapeutic applications
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Summary:Hepatocellular carcinoma (HCC) has high recurrence rates even after curative hepatectomy. Drug therapy for recurrence of HCC is still limited; therefore, identifying new therapeutic targets is urgently needed. We searched for genes that would predict HCC recurrence from intrahepatic metastasis in an exhaustive DNA microarray database by searching genes associated with high early recurrence rate and having higher expression in the tumor area compared to background liver. We detected lysyl oxidase (LOX) and validated the clinical significance of LOX in 358 patients who underwent hepatectomy. Expression of LOX was evaluated by qRT‐ PCR, and immunohistochemical (IHC) staining. High LOX expression group had a significantly higher recurrence rate than the low LOX expression group (2‐year recurrence rate was 64.0% vs 24.2%, P 
ISSN:1347-9032
1349-7006
DOI:10.1111/cas.14010