Abstract 4633: A novel screening marker for breast cancer composed of plasma free amino acid concentrations “AminoIndex”
Authors: Daisuke Shimizu, Takashi Ishikawa, Akihiko Chiba, Yasuhiro Yanagida, Akimitsu Yamada, Yohei Miyagi, Keiichi Kondo, Nobuhiro Saruki, Minoru Yamakado, Toru Mitsushima, Akira Imaizumi, Hiroshi Yamamoto, Naoyuki Okamoto
Journal: Cancer Research (2010)

Abstract Introduction Amino acids balance is changed in patients of various diseases due to metabolic transition while it is maintained in healthy human. For example, it is known to change in liver dysfunction, renal failure, and cancers. Therefore, it is expected that the detection of metabolic transition using amino acid profiles is a promising screening marker of various cancers. We previously showed significant changes of plasma amino acid profiles and discriminating functions using plasma amino acid concentrations “AminoIndex” in various cancer patients including breast cancer. In this study, further possibilities of “AminoIndex” for breast cancer were investigated by case-control study from multiple medical facilities. Subjects and Methods Plasma samples were collected from Japanese breast cancer patients those were hospitalized in three hospitals and finally diagnosed before any medical treatment (N=295). Those of controls were also collected from subjects who were undergone comprehensive medical examination at two hospitals (N=2,147). Plasma amino acid concentrations were measured by LC-MS. Among them, 90 patients (30 from each hospital) in chronological order and 450 age-matched control subjects were chosen as training data set. And the rest (205 patients and 1,697 controls, respectively) were used as test data set to valid the inferred “AminoIndex”. Using training data set, plasma amino acid concentration were compared and then “AminoIndex”, multivariate logistic regression function composed of plasma amino acid concentrations, was inferred to discriminate breast cancer from control subjects. Results Plasma concentrations of several amino acids were significantly changed in breast cancer patients compared to control subjects. Predicted “AminoIndex” for breast cancer was resulted the multivariate logistic function composed with six amino acids. To evaluate the performance of the index predicted, the ROC curve for each predictive score was calculated, and this gave an AUC of ROC of 0.764 using the study data. Then, validation of predicted “AminoIndex” was performed using test data set, resulting almost same diagnostic performance. Furthermore, predicted “AminoIndex” showed notably features; the index could discriminate breast cancer patients almost equally in any stages, and the index showed not only higher discrimination performance than those of existing tumor markers but also distributed independently of the levels of various tumor markers. Therefore, predicted “AminoIndex” would be suitable for screening and early detection of breast cancer patients. Conclusion and Perspectives In this study, we demonstrated that change of plasma amino acid profile would be an indicator of breast cancer and a helpful tool for early detection of breast cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4633.