Circulating AIM as an indicator of liver damage and hepatocellular carcinoma in humans.
<h4>Background</h4>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...
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2014
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oai:doaj.org-article:f15596b44d6a4b0887f4b037aafb7f1f2021-11-25T05:57:11ZCirculating AIM as an indicator of liver damage and hepatocellular carcinoma in humans.1932-620310.1371/journal.pone.0109123https://doaj.org/article/f15596b44d6a4b0887f4b037aafb7f1f2014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0109123https://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusion</h4>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.Tomoko YamazakiMayumi MoriSatoko AraiRyosuke TateishiMasanori AbeMihoko BanAkemi NishijimaMaki MaedaTakeharu AsanoToshihiro KaiKiyohiro IzuminoJun TakahashiKayo AoyamaSei HaradaToru TakebayashiToshiaki GunjiShin OhnishiShinji SetoYukio YoshidaYoichi HiasaKazuhiko KoikeKen-ichi YamamuraKen-ichiro InoueToru MiyazakiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 10, p e109123 (2014) |
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DOAJ |
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EN |
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Medicine R Science Q |
| spellingShingle |
Medicine R Science Q 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 Hiasa Kazuhiko Koike Ken-ichi Yamamura Ken-ichiro Inoue Toru Miyazaki Circulating AIM as an indicator of liver damage and hepatocellular carcinoma in humans. |
| description |
<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusion</h4>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. |
| format |
article |
| author |
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 Hiasa Kazuhiko Koike Ken-ichi Yamamura Ken-ichiro Inoue Toru Miyazaki |
| author_facet |
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 Hiasa Kazuhiko Koike Ken-ichi Yamamura Ken-ichiro Inoue Toru Miyazaki |
| author_sort |
Tomoko Yamazaki |
| title |
Circulating AIM as an indicator of liver damage and hepatocellular carcinoma in humans. |
| title_short |
Circulating AIM as an indicator of liver damage and hepatocellular carcinoma in humans. |
| title_full |
Circulating AIM as an indicator of liver damage and hepatocellular carcinoma in humans. |
| title_fullStr |
Circulating AIM as an indicator of liver damage and hepatocellular carcinoma in humans. |
| title_full_unstemmed |
Circulating AIM as an indicator of liver damage and hepatocellular carcinoma in humans. |
| title_sort |
circulating aim as an indicator of liver damage and hepatocellular carcinoma in humans. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/f15596b44d6a4b0887f4b037aafb7f1f |
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