Brief Article
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World J Gastroenterol. Sep 28, 2013; 19(36): 6084-6092
Published online Sep 28, 2013. doi: 10.3748/wjg.v19.i36.6084
Overexpression of insulin-like growth factor-I receptor as a pertinent biomarker for hepatocytes malignant transformation
Xiao-Di Yan, Min Yao, Li Wang, Hai-Jian Zhang, Mei-Juan Yan, Xing Gu, Yun Shi, Jie Chen, Zhi-Zhen Dong, Deng-Fu Yao
Xiao-Di Yan, Hai-Jian Zhang, Deng-Fu Yao, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Min Yao, Li Wang, Mei-Juan Yan, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
Xing Gu, Yun Shi, Jie Chen, Department of Clinical Oncology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Zhi-Zhen Dong, Department of Diagnostics, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Author contributions: Yan XD and Yao M contributed equally to this work, designed research, analyzed data and wrote the paper; Wang L, Yan MJ and Gu X carried out the experiments; Yao M, Shi Y, Chen J, Zhang HJ and Yan XD performed the experiments; Xing Gu completed immunohistochemical and HE staining; Dong ZZ made critical review of the manuscript; Yao DF is the guarantor.
Supported by The Society Development of Nantong, HS2012039; Jiangsu Health Projects, BL2012053, K201102; the Priority Academic Program Development of Jiangsu, and the International S and T Cooperation Program, 2013DFA32150 of China
Correspondence to: Deng-Fu Yao, MD, PhD, Professor, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, 20 West Temple Road, Nantong 226001, Jiangsu Province, China. yaodf@ahnmc.com
Telephone: +86-513-85052297 Fax: +86-513-85052254
Received: June 15, 2013
Revised: July 20, 2013
Accepted: August 20, 2013
Published online: September 28, 2013
Processing time: 103 Days and 4.1 Hours
Abstract

AIM: To investigate the dynamic features of insulin-like growth factor-I receptor (IGF-IR) expression in rat hepatocarcinogenesis, and the relationship between IGF-IR and hepatocytes malignant transformation at mRNA or protein level.

METHODS: Hepatoma models were made by inducing with 2-fluorenylacetamide (2-FAA) on male Sprague-Dawley rats. Morphological changes of hepatocytes were observed by pathological Hematoxylin and eosin staining, the dynamic expressions of liver and serum IGF-IR were quantitatively analyzed by an enzyme-linked immunosorbent assay. The distribution of hepatic IGF-IR was located by immunohistochemistry. The fragments of IGF-IR gene were amplified by reverse transcription-polymerase chain reaction, and confirmed by sequencing.

RESULTS: Rat hepatocytes after induced by 2-FAA were changed dynamically from granule-like degeneration, precancerous to hepatoma formation with the progressing increasing of hepatic mRNA or IGF-IR expression. The incidences of liver IGF-IR, IGF-IR mRNA, specific IGF-IR concentration (ng/mg wet liver), and serum IGF-IR level (ng/mL) were 0.0%, 0.0%, 0.63 ± 0.17, and 1.33 ± 0.47 in the control; 50.0%, 61.1%, 0.65 ± 0.2, and 1.51 ± 0.46 in the degeneration; 88.9%, 100%, 0.66 ± 0.14, and 1.92 ± 0.29 in the precancerosis; and 100%, 100%, 0.96 ± 0.09, and 2.43 ± 0.57 in the cancerous group, respectively. IGF-IR expression in the cancerous group was significantly higher (P < 0.01) than that in any of other groups at mRNA or protein level. The closely positive IGF-IR relationship was found between livers and sera (r = 0.91, t = 14.222, P < 0.01), respectively.

CONCLUSION: IGF-IR expression may participate in rat hepatocarcinogenesis and its abnormality should be an early marker for hepatocytes malignant transformation.

Keywords: Hepatoma; Insulin-like growth factor-I receptor; Immunohistochemistry; Gene amplification; Sequencing; Rat hepatoma model

Core tip: The abnormality of insulin-like growth factor-I receptor (IGF-IR) expression was progressively increased in hepatocarcinogenesis at mRNA or protein level, and there was a positive correlation between circulating blood and liver IGF-IR, suggesting that the over-expression of liver IGF-IR release into blood, and serum IGF-IR should be an early useful marker for monitoring malignant transformation of rat hepatocytes.