Article on "Plasma free amino acid profiling of five types of cancer patients and its
application for early detection"
Published in Online Scientific Journal PLoS ONE

TOKYO, September 8, 2011 - Ajinomoto Co., Inc. (Ajinomoto), together with a group led by Dr. Yohei Miyagi of the Molecular Pathology and Genetics Division and Dr. Naoyuki Okamoto of the Cancer Prevention and Control Division of Kanagawa Cancer Center Research Institute, has been conducting research on alterations in the plasma amino acid profiles in the cancer patients with five types of cancer (lung, gastric, colorectal, breast and prostate cancer). In a large-scale, multicenter clinical trial, Miyagi, et al. found that the plasma amino acid profiles in cancer patients were significantly different from those in healthy individuals, that these differences were recognizable even in the patients with early stage cancer, and that multivariate analysis of plasma amino acid profiles was potentially applicable in early detection of cancer.
These findings were published on September 7, 2011 in the online journal PLoS ONE.*

* PLoS ONE: An open-access online scientific journal published by the Public Library of Science (PLoS), a nonprofit organization based in San Francisco, California, U.S.A. It is an important media outlet for papers in various fields, particularly biology and medicine.

Ajinomoto has developed "AminoIndex Technology" that statistically analyzes and indexes alterations in the plasma amino acid profiles to clarify health condition and disease risk. Amino acid concentration in the blood is regulated strictly by the body's homeostatic functions, but numerous reports mentioned that this balance was influenced by various diseases, and altered compared to healthy individuals.1

Summary of the Article
Alteration of plasma amino acid profiles of cancer patients have been reported previously, but all of these reports were limited to small-scale studies. This study collected subjects on a larger scale, including early-stage cancer patients, from multiple medical institutes. Case-control studies were then conducted to verify whether plasma amino acid profiles of cancer patients could be discriminated from those of control group statistically.

In the study, plasma amino acid profiles were compared among 928 cancer patients, consisting of 130-200 patients for each type of cancer, and a total of 4,618 healthy subjects comprising 650-1,000 controls for each type of cancer.

The findings showed that
   1)  Amino acid profiles of cancer patients were significantly different from those in healthy individuals, and, further, that there were changes in some amino acids that were common to all cancer types, as well as changes in amino acids that were specific to each cancer type (see figure below).
   2)  Alteration in plasma amino acid profiles in the cancer patients could be detected even in patients with early-stage cancer.
Moreover, discriminant analysis, a type of multivariate analysis, could discriminate clearly the cancer patients from control groups in terms of the area under the ROC curve2 (>0.75 for each cancer). Those results showed the possibility of the early detection of cancer patients using this discriminant function.

Figure  Changes in Amino Acid Concentration Balance in Five Types of Cancer Patients

By applying the knowledge obtained from this study, "AminoIndex Technology" has potential for use in early detection of multiple types of cancer in blood samples with a high degree of precision and convenience. This will increase opportunities for early treatment of cancer which will lead to fewer cancer deaths, the leading cause of death in Japan, and lower medical care expenses related to cancer treatment. In addition to extending the applicability of "AminoIndex Technology" to other diseases, Ajinomoto also plans to determine the mechanism that alterations in plasma amino acid profiles observed in the cancer patients and will conduct further research, including cohort studies.3

Title of the Study and Authors
Plasma free amino acid profiling of five types of cancer patients and its application for early detection
Yohei Miyagi*1, Masahiko Higashiyama2, Akira Gochi3, Makoto Akaike1, Takashi Ishikawa4, Takeshi Miura1, Nobuhiro Saruki5, Etsuro Bando6, Hideki Kimura7, Fumio Imamura2, Masatoshi Moriyama8, Ichiro Ikeda9, Akihiko Chiba1, Fumihiro Oshita1, Akira Imaizumi10, Hiroshi Yamamoto10, Hiroshi Miyano10, Katsuhisa Horimoto11, Osamu Tochikubo12, Toru Mitsushima13, Minoru Yamakado14, and Naoyuki Okamoto1
*1. Kanagawa Cancer Center, 2. Osaka Medical Center for Cancer and Cardiovascular Diseases,
3. Okayama University Hospital, 4. Yokohama City University Medical Center, 5. Gunma Prefectural Cancer Center, 6. Shizuoka Prefectural Cancer Center, 7. Chiba Prefectural Cancer Center, 8. Yokohama Municipal Citizen's Hospital, 9. Yokohama Minami Kyosai Hospital, 10. Institute for Innovation, Ajinomoto Co., Inc., 11. National Institute of Advanced Industrial Science and Technology, 12. Kanagawa Health Service Association, 13. Kameda Medical Center Makuhari, 14. Mitsui Memorial Hospital

   1.  "Amino acids and life-style related diseases: application of new aminograms in life science," Osamu Tochikubo and Toshihiko Ando, Women's Nutrition University Press (2010), was used as a reference. Articles on "AminoIndex Technology" released previously by Ajinomoto:
1) Noguchi, et al. (2006) Am J Clin Nutr 83: 513S-519S.
2) Zhang, et al. (2006) Hepatol Res 34: 170-177.
3) Kimura, et al. (2009) Curr Opin Clin Nutr Metab Care 12: 49-53.

Previously published articles on cancer detection using "AminoIndex Technology:"
1) Okamoto, et al. (2009) Int J Med Med Sci 1 1-8
2) Maeda, et al. (2010) BMC Cancer 10.690
3) Miura, et al. (2011) Ningen Dock 26.51-55
   2.  Area under the ROC Curve
The ROC (receiver operating characteristic) curve is an indicator expressing the probability of a correct diagnosis from a given test. The area under this curve ranges from 0.5 to 1, with the ideal test having a value of 1. In general, a value of 0.7 or higher indicates an effective test, and a value of 0.8 or higher indicates a highly accurate test.
   3.  Cohort Study
An epidemiological approach in which a group of patients is followed over time to check the incidence of disease. For example, trial subjects may be classified into those determined to be at high risk of disease and those determined to be at low risk based on the results of amino acid profiling analysis. The future incidence of disease is then compared to look for a causal relationship between the disease and amino acid profiles.

About Ajinomoto
Ajinomoto is a global manufacturer of high-quality seasonings, processed foods, beverages, amino acids, pharmaceuticals and specialty chemicals. For many decades Ajinomoto has contributed to food culture and human health through wide-ranging application of amino acid technologies. Today, the company is becoming increasingly involved with solutions for improved food resources, human health and global sustainability.
Founded in 1909 and now operating in 25 countries, Ajinomoto had net sales of JPY 1,170.8 billion (USD 12.8 billion) in fiscal 2010. For more about Ajinomoto (TYO: 2802), visit

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