Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

The significance and robustness of a plasma free amino acid (PFAA) profile-based multiplex function for detecting lung cancer

Authors: Masato Shingyoji, Toshihiko Iizasa, Masahiko Higashiyama, Fumio Imamura, Nobuhiro Saruki, Akira Imaizumi, Hiroshi Yamamoto, Takashi Daimon, Osamu Tochikubo, Toru Mitsushima, Minoru Yamakado, Hideki Kimura

Published in: BMC Cancer | Issue 1/2013

Login to get access

Abstract

Background

We have recently reported on the changes in plasma free amino acid (PFAA) profiles in lung cancer patients and the efficacy of a PFAA-based, multivariate discrimination index for the early detection of lung cancer. In this study, we aimed to verify the usefulness and robustness of PFAA profiling for detecting lung cancer using new test samples.

Methods

Plasma samples were collected from 171 lung cancer patients and 3849 controls without apparent cancer. PFAA levels were measured by high-performance liquid chromatography (HPLC)–electrospray ionization (ESI)–mass spectrometry (MS).

Results

High reproducibility was observed for both the change in the PFAA profiles in the lung cancer patients and the discriminating performance for lung cancer patients compared to previously reported results. Furthermore, multivariate discriminating functions obtained in previous studies clearly distinguished the lung cancer patients from the controls based on the area under the receiver-operator characteristics curve (AUC of ROC = 0.731 ~ 0.806), strongly suggesting the robustness of the methodology for clinical use. Moreover, the results suggested that the combinatorial use of this classifier and tumor markers improves the clinical performance of tumor markers.

Conclusions

These findings suggest that PFAA profiling, which involves a relatively simple plasma assay and imposes a low physical burden on subjects, has great potential for improving early detection of lung cancer.
Appendix
Available only for authorised users
Literature
1.
Hunter MP, Ismail N, Zhang X, Aguda BD, Lee EJ, Yu L, Xiao T, Schafer J, Lee ML, Schmittgen TD, et al: Detection of microRNA expression in human peripheral blood microvesicles. PLoS One. 2008, 3 (11): e3694-10.1371/journal.pone.0003694.CrossRefPubMedPubMedCentral
2.
Roth C, Kasimir-Bauer S, Pantel K, Schwarzenbach H: Screening for circulating nucleic acids and caspase activity in the peripheral blood as potential diagnostic tools in lung cancer. Mol Oncol. 2011, 5 (3): 281-291. 10.1016/j.molonc.2011.02.002.CrossRefPubMed
3.
Roth C, Rack B, Muller V, Janni W, Pantel K, Schwarzenbach H: Circulating microRNAs as blood-based markers for patients with primary and metastatic breast cancer. Breast Canc Res. 2010, 12 (6): R90-10.1186/bcr2766.CrossRef
4.
Chadeau-Hyam M, Ebbels TM, Brown IJ, Chan Q, Stamler J, Huang CC, Daviglus ML, Ueshima H, Zhao L, Holmes E, et al: Metabolic profiling and the metabolome-wide association study: significance level for biomarker identification. J Proteome Res. 2010, 9 (9): 4620-4627. 10.1021/pr1003449.CrossRefPubMedPubMedCentral
5.
Lee K, Hwang D, Yokoyama T, Stephanopoulos G, Stephanopoulos GN, Yarmush ML: Identification of optimal classification functions for biological sample and state discrimination from metabolic profiling data. Bioinformatics. 2004, 20 (6): 959-969. 10.1093/bioinformatics/bth015.CrossRefPubMed
6.
Kim Y, Koo I, Jung BH, Chung BC, Lee D: Multivariate classification of urine metabolome profiles for breast cancer diagnosis. BMC Bioinforma. 2010, 11 (2): S4-CrossRef
7.
Nolen B, Velikokhatnaya L, Marrangoni A, De Geest K, Lomakin A, Bast RC, Lokshin A: Serum biomarker panels for the discrimination of benign from malignant cases in patients with an adnexal mass. Gynecol Oncol. 2010, 117 (3): 440-445. 10.1016/j.ygyno.2010.02.005.CrossRefPubMedPubMedCentral
8.
Pasikanti KK, Esuvaranathan K, Ho PC, Mahendran R, Kamaraj R, Wu QH, Chiong E, Chan EC: Noninvasive urinary metabonomic diagnosis of human bladder cancer. J Proteome Res. 2010, 9 (6): 2988-2995. 10.1021/pr901173v.CrossRefPubMed
9.
Qiu Y, Cai G, Su M, Chen T, Zheng X, Xu Y, Ni Y, Zhao A, Xu LX, Cai S, et al: Serum metabolite profiling of human colorectal cancer using GC-TOFMS and UPLC-QTOFMS. J Proteome Res. 2009, 8 (10): 4844-4850. 10.1021/pr9004162.CrossRefPubMed
10.
Qiu Y, Patwa TH, Xu L, Shedden K, Misek DE, Tuck M, Jin G, Ruffin MT, Turgeon DK, Synal S, et al: Plasma glycoprotein profiling for colorectal cancer biomarker identification by lectin glycoarray and lectin blot. J Proteome Res. 2008, 7 (4): 1693-1703. 10.1021/pr700706s.CrossRefPubMedPubMedCentral
11.
Rocha CM, Barros AS, Gil AM, Goodfellow BJ, Humpfer E, Spraul M, Carreira IM, Melo JB, Bernardo J, Gomes A, et al: Metabolic profiling of human lung cancer tissue by 1H high resolution magic angle spinning (HRMAS) NMR spectroscopy. J Proteome Res. 2010, 9 (1): 319-332. 10.1021/pr9006574.CrossRefPubMed
12.
Urayama S, Zou W, Brooks K, Tolstikov V: Comprehensive mass spectrometry based metabolic profiling of blood plasma reveals potent discriminatory classifiers of pancreatic cancer. Rapid Commun Mass Spectrom. 2010, 24 (5): 613-620. 10.1002/rcm.4420.CrossRefPubMed
13.
Felig P, Marliss E, Ohman JL, Cahill CF: Plasma amino acid levels in diabetic ketoacidosis. Diabetes. 1970, 19 (10): 727-728.CrossRefPubMed
14.
Felig P, Wahren J, Raf L: Evidence of inter-organ amino-acid transport by blood cells in humans. Proc Natl Acad Sci USA. 1973, 70 (6): 1775-1779. 10.1073/pnas.70.6.1775.CrossRefPubMedPubMedCentral
15.
Fischer JE, Funovics JM, Aguirre A, James JH, Keane JM, Wesdorp RI, Yoshimura N, Westman T: The role of plasma amino acids in hepatic encephalopathy. Surgery. 1975, 78 (3): 276-290.PubMed
16.
Fischer JE, Rosen HM, Ebeid AM, James JH, Keane JM, Soeters PB: The effect of normalization of plasma amino acids on hepatic encephalopathy in man. Surgery. 1976, 80 (1): 77-91.PubMed
17.
Kimura T, Noguchi Y, Shikata N, Takahashi M: Plasma amino acid analysis for diagnosis and amino acid-based metabolic networks. Curr Opin Clin Nutr Metab Care. 2009, 12 (1): 49-53. 10.1097/MCO.0b013e3283169242.CrossRefPubMed
18.
Noguchi Y, Zhang QW, Sugimoto T, Furuhata Y, Sakai R, Mori M, Takahashi M, Kimura T: Network analysis of plasma and tissue amino acids and the generation of an amino index for potential diagnostic use. Am J Clin Nutr. 2006, 83 (2): 513S-519S.PubMed
19.
Cascino A, Cangiano C, Ceci F, Franchi F, Mineo T, Mulieri M, Muscaritoli M, Rossi Fanelli F: Increased plasma free tryptophan levels in human cancer: a tumor related effect?. Anticancer Res. 1991, 11 (3): 1313-1316.PubMed
20.
Cascino A, Muscaritoli M, Cangiano C, Conversano L, Laviano A, Ariemma S, Meguid MM, Rossi Fanelli F: Plasma amino acid imbalance in patients with lung and breast cancer. Anticancer Res. 1995, 15 (2): 507-510.PubMed
21.
Kubota A, Meguid MM, Hitch DC: Amino acid profiles correlate diagnostically with organ site in three kinds of malignant tumors. Cancer. 1992, 69 (9): 2343-2348. 10.1002/1097-0142(19920501)69:9<2343::AID-CNCR2820690924>3.0.CO;2-S.CrossRefPubMed
22.
Lai HS, Lee JC, Lee PH, Wang ST, Chen WJ: Plasma free amino acid profile in cancer patients. Semin Canc Biol. 2005, 15 (4): 267-276. 10.1016/j.semcancer.2005.04.003.CrossRef
23.
Laviano A, Cascino A, Muscaritoli M, Fanfarillo F, Rossi Fanelli F: Tumor-induced changes in host metabolism: a possible role for free tryptophan as a marker of neoplastic disease. Adv Exp Med Biol. 2003, 527: 363-366. 10.1007/978-1-4615-0135-0_41.CrossRefPubMed
24.
Naini AB, Dickerson JW, Brown MM: Preoperative and postoperative levels of plasma protein and amino acid in esophageal and lung cancer patients. Cancer. 1988, 62 (2): 355-360. 10.1002/1097-0142(19880715)62:2<355::AID-CNCR2820620221>3.0.CO;2-E.CrossRefPubMed
25.
Norton JA, Gorschboth CM, Wesley RA, Burt ME, Brennan MF: Fasting plasma amino acid levels in cancer patients. Cancer. 1985, 56 (5): 1181-1186. 10.1002/1097-0142(19850901)56:5<1181::AID-CNCR2820560535>3.0.CO;2-8.CrossRefPubMed
26.
Proenza AM, Oliver J, Palou A, Roca P: Breast and lung cancer are associated with a decrease in blood cell amino acid content. J Nutr Biochem. 2003, 14 (3): 133-138. 10.1016/S0955-2863(02)00225-5.CrossRefPubMed
27.
Vissers YL, Dejong CH, Luiking YC, Fearon KC, von Meyenfeldt MF, Deutz NE: Plasma arginine concentrations are reduced in cancer patients: evidence for arginine deficiency?. Am J Clin Nutr. 2005, 81 (5): 1142-1146.PubMed
28.
Fontana S, Alessandro R, Barranca M, Giordano M, Corrado C, Zanella-Cleon I, Becchi M, Kohn EC, De Leo G: Comparative proteome profiling and functional analysis of chronic myelogenous leukemia cell lines. J Proteome Res. 2007, 6 (11): 4330-4342. 10.1021/pr0704128.CrossRefPubMed
29.
Shimbo K, Kubo S, Harada Y, Oonuki T, Yokokura T, Yoshida H, Amao M, Nakamura M, Kageyama N, Yamazaki J, et al: Automated precolumn derivatization system for analyzing physiological amino acids by liquid chromatography/mass spectrometry. Biomed Chromatogr. 2009, 24 (7): 683-691. 10.1002/bmc.1346.CrossRef
30.
Shimbo K, Oonuki T, Yahashi A, Hirayama K, Miyano H: Precolumn derivatization reagents for high-speed analysis of amines and amino acids in biological fluid using liquid chromatography/electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom. 2009, 23 (10): 1483-1492. 10.1002/rcm.4026.CrossRefPubMed
31.
Shimbo K, Yahashi A, Hirayama K, Nakazawa M, Miyano H: Multifunctional and highly sensitive precolumn reagents for amino acids in liquid chromatography/tandem mass spectrometry. Anal Chem. 2009, 81 (13): 5172-5179. 10.1021/ac900470w.CrossRefPubMed
32.
Maeda J, Higashiyama M, Imaizumi A, Nakayama T, Yamamoto H, Daimon T, Yamakado M, Imamura F, Kodama K: Possibility of multivariate function composed of plasma amino acid profiles as a novel screening index for non-small cell lung cancer: a case control study. BMC Canc. 2010, 10 (1): 690-10.1186/1471-2407-10-690.CrossRef
33.
Okamoto N, Miyagi Y, Chiba A, Akaike M, Shiozawa M, Imaizumi A, Yamamoto H, Ando T, Yamakado M, Tochikubo O: Diagnostic modeling with differences in plasma amino acid profiles between non-cachectic colorectal/breast cancer patients and healthy individuals. Int J Med Med Sci. 2009, 1 (1): 1-8.
34.
Miyagi Y, Higashiyama M, Gochi A, Akaike M, Ishikawa T, Miura T, Saruki N, Bando E, Kimura H, Imamura F, et al: Plasma free amino acid profiling of five types of cancer patients and its application for early detection. PLoS One. 2011, 6 (9): e24143-10.1371/journal.pone.0024143.CrossRefPubMedPubMedCentral
35.
Okamoto N: Cancer screening using “AminoIndex Technology”. Ningen Dock. 2011, 26 (3): 454-466.
36.
Asamura H, Goya T, Koshiishi Y, Sohara Y, Eguchi K, Mori M, Nakanishi Y, Tsuchiya R, Shimokata K, Inoue H, et al: A Japanese Lung Cancer Registry study: prognosis of 13,010 resected lung cancers. J Thorac Oncol. 2008, 3 (1): 46-52. 10.1097/JTO.0b013e31815e8577.CrossRefPubMed
37.
Sumitani M, Takifuji N, Nanjyo S, Imahashi Y, Kiyota H, Takeda K, Yamamoto R, Tada H: Clinical relevance of sputum cytology and chest X-ray in patients with suspected lung tumors. Intern Med. 2008, 47 (13): 1199-1205. 10.2169/internalmedicine.47.0777.CrossRefPubMed
38.
Sobin L, Wittekind C: TNM Classification of Malignant Tumours, Sixth Edition. 2002, New York: Wiley-Liss
39.
Ando S, Kimura H, Iwai N, Kakizawa K, Shima M, Ando M: The significance of tumour markers as an indication for mediastinoscopy in non-small cell lung cancer. Respirology. 2003, 8 (2): 163-167. 10.1046/j.1440-1843.2003.00443.x.CrossRefPubMed
40.
Hanley JA, McNeil BJ: The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982, 143 (1): 29-36.CrossRefPubMed
41.
Molina R, Auge JM, Filella X, Vinolas N, Alicarte J, Domingo JM, Ballesta AM: Pro-gastrin-releasing peptide (proGRP) in patients with benign and malignant diseases: comparison with CEA, SCC, CYFRA 21–1 and NSE in patients with lung cancer. Anticancer Res. 2005, 25 (3A): 1773-1778.PubMed
Metadata
Title
The significance and robustness of a plasma free amino acid (PFAA) profile-based multiplex function for detecting lung cancer
Authors
Masato Shingyoji
Toshihiko Iizasa
Masahiko Higashiyama
Fumio Imamura
Nobuhiro Saruki
Akira Imaizumi
Hiroshi Yamamoto
Takashi Daimon
Osamu Tochikubo
Toru Mitsushima
Minoru Yamakado
Hideki Kimura
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-77

Other articles of this Issue 1/2013

BMC Cancer 1/2013 Go to the issue

Research article

Germline mutation in the RAD51B gene confers predisposition to breast cancer

Research article

Differential effects of garcinol and curcumin on histone and p53 modifications in tumour cells

Research article

An explorative analysis of ERCC1-19q13 copy number aberrations in a chemonaive stage III colorectal cancer cohort

Study protocol

“EXHALE”: exercise as a strategy for rehabilitation in advanced stage lung cancer patients: a randomized clinical trial comparing the effects of 12 weeks supervised exercise intervention versus usual care for advanced stage lung cancer patients

Research article

Implication from thyroid function decreasing during chemotherapy in breast cancer patients: chemosensitization role of triiodothyronine

Research article

Preoperative serum CA 72.4 as prognostic factor of recurrence and death, especially at TNM stage II, for colorectal cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits