Circulating AIM as an indicator of liver damage and hepatocellular carcinoma in humans

Tomoko Yamazaki, Mayumi Mori, Satoko Arai, Ryosuke Tateishi, Masanori Abe, Mihoko Ban, Akemi Nishijima, Maki Maeda, Takeharu Asano, Toshihiro Kai, Kiyohiro Izumino, Jun Takahashi, Kayo Aoyama, Sei Harada, Toru Takebayashi, Toshiaki Gunji, Shin Ohnishi, Shinji Seto, Yukio Yoshida, Yoichi HiasaKazuhiko Koike, Ken Ichi Yamamura, Ken Ichiro Inoue, Toru Miyazaki

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Abstract

Background: Hepatocellular carcinoma (HCC), the fifth most common cancer type and the third highest cause of cancer death worldwide, develops in different types of liver injuries, and is mostly associated with cirrhosis. However, non-alcoholic fatty liver disease often causes HCC with less fibrosis, and the number of patients with this disease is rapidly increasing. The high mortality rate and the pathological complexity of liver diseases and HCC require blood biomarkers that accurately reflect the state of liver damage and presence of HCC. Methods and Findings: Here we demonstrate that a circulating protein, apoptosis inhibitor of macrophage (AIM) may meet this requirement. A large-scale analysis of healthy individuals across a wide age range revealed a mean blood AIM of 4.99±1.8 μg/ml in men and 6.06±2.1 μg/ml in women. AIM levels were significantly augmented in the younger generation (20s-40s), particularly in women. Interestingly, AIM levels were markedly higher in patients with advanced liver damage, regardless of disease type, and correlated significantly with multiple parameters representing liver function. In mice, AIM levels increased in response to carbon tetrachloride, confirming that the high AIM observed in humans is the result of liver damage. In addition, carbon tetrachloride caused comparable states of liver damage in AIM-deficient and wild-type mice, indicating no influence of AIM levels on liver injury progression. Intriguingly, certain combinations of AIM indexes normalized to liver marker score significantly distinguished HCC patients from non-HCC patients and thus could be applicable for HCC diagnosis. Conclusion: AIM potently reveals both liver damage and HCC. Thus, our results may provide the basis for novel diagnostic strategies for this widespread and fatal disease.

Original languageEnglish
Article numbere109123
JournalPloS one
Volume9
Issue number10
DOIs
Publication statusPublished - 2014 Oct 10

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Yamazaki, T., Mori, M., Arai, S., Tateishi, R., Abe, M., Ban, M., Nishijima, A., Maeda, M., Asano, T., Kai, T., Izumino, K., Takahashi, J., Aoyama, K., Harada, S., Takebayashi, T., Gunji, T., Ohnishi, S., Seto, S., Yoshida, Y., ... Miyazaki, T. (2014). Circulating AIM as an indicator of liver damage and hepatocellular carcinoma in humans. PloS one, 9(10), [e109123]. https://doi.org/10.1371/journal.pone.0109123