The performance of a novel amino acid multivariate index for detecting lung cancer: A case control study in Korea

Kim, Hee Joung; Jang, Seung Hun; Ryu, Jeong‐Seon; Lee, Jeong Eun; Kim, Young Chul; Lee, Min Ki; Jang, Tae Won; Lee, Shin-Yup; Nakamura, Hidehiro; Nishikata, Natsumi; Mori, Maiko; Noguchi, Yasushi; Miyano, Hiroshi; Lee, Kye Young

doi:10.1016/j.lungcan.2015.10.006

Cited by 46 publications

(41 citation statements)

References 29 publications

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“…The class of metabolites, which is currently the most explored in blood of NSCLC patients, is free amino acids. Some targeted metabolomic profiling focusing on determination of free amino acid levels in NSCLC has appeared in recent years (Klupczynska et al 2016a; Kim et al 2015; Shingyoji et al 2013; Maeda et al 2010). The analyses of amino acid profiles did not reveal one specific molecule that can play a role of NSCLC marker, but they emphasized the potential of using a multi-marker panel in lung cancer detection.…”

Section: Discussionmentioning

confidence: 99%

Study of early stage non-small-cell lung cancer using Orbitrap-based global serum metabolomics

Klupczynska

Dereziński

Garrett

et al. 2017

J Cancer Res Clin Oncol

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PurposeThe aim of the project was to apply ultra-high-performance liquid chromatography–quadrupole-Orbitrap-high-resolution mass spectrometry for serum metabolite profiling of non-small-cell lung cancer (NSCLC). This Orbitrap-based methodology has been applied for a study of NSCLC potential markers for the first time.MethodsAfter extraction using protein precipitation, sera were separated on the ACE Excel 2 C18-PFP (100 × 2.1 mm, 2.0 µm) column using gradient elution and analyzed within the range of 70–1000 m/z. Only patients with early stage disease (stages IA–IIB) were included in the study, providing opportunity to find biomarkers for early lung cancer detection. The resulting metabolite profiles were subjected to univariate and multivariate statistical tests.Results36 features were found significantly changed between NSCLC group and controls after FDR adjustment and 19 were identified using various metabolite databases (in-house library, HMDB, mzCloud). The study revealed a number of NSCLC biomarker candidates which belong to such compound classes as acylcarnitines, organic acids, and amino acids. Multivariate ROC curve built using 12 identified metabolites was characterized by AUC = 0.836 (0.722–0.946). There were no significant differences in the serum metabolite profiles between two most common histological types of lung cancer—adenocarcinoma and squamous cell carcinoma.ConclusionsThrough identification of novel potential tumor markers, Orbitrap-based global metabolic profiling is a useful strategy in cancer research. Our study can accelerate development of new diagnostic and therapeutic strategies in NSCLC. The metabolites involved in discrimination between NSCLC patients and the control subjects should be further explored using a targeted approach.Electronic supplementary materialThe online version of this article (doi:10.1007/s00432-017-2347-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Study of early stage non-small-cell lung cancer using Orbitrap-based global serum metabolomics

Klupczynska

Dereziński

Garrett

et al. 2017

J Cancer Res Clin Oncol

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“…The AICS™ test is currently performed to detect 7 types of cancers, and the AICS (lung) test for lung cancer is widely used in health and cancer screening in Japan. Several promising studies on similar or the same concepts have been reported abroad [5,21,22,24,25]. According to our previous ndings [1,8,9], this test may be an optional tool for the early detection of lung cancer, regardless of the tumor stage or progression, in contrast to other tumor markers, such as serum CEA and CYFRA.…”

Section: Discussionmentioning

confidence: 63%

Preoperative AICS (lung) abnormalities predict postoperative recurrence in patients undergoing curative resection for non-small cell lung cancer

Higashiyama¹,

Miyazaki²,

Yamamoto³

et al. 2020

Preprint

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[Background] AminoIndexTM Cancer Screening (AICS (lung)) was developed as a screening test for lung cancer using a multivariate analysis of plasma-free amino acid (PFAA) profiles. According to the developed index composed of PFAA, the probability of lung cancer was categorized into AICS (lung) ranks A, B, and C in order of increasing risk. The aim of the present study was to investigate the relationship between the preoperative AICS (lung) rank and surgical outcomes in patients who underwent curative resection for non-small cell lung cancer (NSCLC).[Methods] Preoperative blood samples were collected from 297 patients who underwent curative resection for NSCLC between 2006 and 2015. PFAA concentrations were measured. The relationship between the preoperative AICS (lung) rank and clinicopathological factors was examined. The effects of the preoperative AICS (lung) rank on postoperative outcomes were also analyzed.[Results] The AICS (lung) rank was A in 93 patients (31.3%), B in 82 (27.6%), and C in 122 (41.1%). The AICS (lung) rank did not correlate with any clinicopathological factors, except for age. Based on follow-up data (median follow-up period of 6 years), postoperative recurrence was observed in 22 rank A patients (23.7%), 15 rank B (18.3%) and 49 rank C (40.2%). In the univariate analysis, preoperative AICS (lung) rank C was a worse factor of recurrence-free survival (p=0.0002). The multivariate analysis identified preoperative AICS (lung) rank C (HR: 2.17, p=0.0005) as a significant predictor of postoperative recurrence, particularly in patients with early-stage disease or adenocarcinoma. [Conclusion] Preoperative AICS (lung) abnormalities are a high-risk predictor of postoperative recurrence in NSCLC patients undergoing curative resection.

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“…The pathological changes in lung tissues were assessed by decreased lung metabolism via depletion of argenine, cysteine, glutamine, histidine, leucine, methionine, phenyl alanine, proline and lysine in all the treated groups. The decrease amino acids reflect the hypoxic stress affected the lung tissues as detected by increased fibrosis of maternal lung and hyperplasia and necrotic foci in newborn rats [40].…”

Section: Discussionmentioning

confidence: 97%

“…Kim et al [40] reported a decrease of threonine, citrulline, histidine and tryptophan and increase in proline, isoleucine, phenylalanine and ornithine in lung of Korean cancer patients with advanced pulmonary disease showed inverse correlation with alanine, phenylalanine and tyrosine, however citrulline and tryphtophane were markedly changed in relation to energy intake [41].…”

Section: Discussionmentioning

confidence: 98%

Markers of Heart, Lung and Dorsal Aorta Damage of Mother Rats and Their Neonates Post Therapeutic Treatment with Doxorubicin, Cisplatin and 5-Flurouracil

El-Ghawet¹,

Gadallah²,

El‐Mansi³

et al. 2017

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Aim: Recently, there is an increased average of developing cancers. Though, the chemotherapeutic-treatment is unfavorable during pregnancy due to its harmful effects on developing fetuses, physicians have two ways to minimize these effects either by termination of the pregnancy or minimizing its side effects. The present work aimed to illustrate the susceptibility of cardiac, lung and dorsal aorta function to the widely applicable drugs doxorubicin and cisplatin as well as 5-flurouracil. Materials and Methods: Mother albino rats were arranged into four-groups (control, doxorubicin, cisplatin and 5-flurouracil-treated groups). Each pregnant rat received intraperitoneal administration of 0.2 mg/kg body weight at 10 th and 14 th day of gestation and sacrificed at parturition (two doses). At parturition, serum of mother rats used to assess troponin I, heat shock protein 70, 8-hydroxydeoxyguanosine, vascular endothelial growth factor and adhesion molecules (ICAM-1 & VCAM-1). Isoenzyme electrophoresis of alkaline and acid phosphatases, glucose-6-phosphate dehydrogenase and lactic dehydrogenase were estimated in serum, myocardium and dorsal aorta of mother rats. The myocardium and lung were processed for histopathological investigations for both mothers and their offspring. Single strand (comet assay) and double strand DNA damage were carried out in heart and dorsal aorta of mother rats. Results: The present finding revealed that there are detected alterations of myocardial markers and lung amino acid metabolism as well as disruption of myocardial isoenzymes. 83Chinese Medicine DNA damage of myocardium and dorsal aorta were observed. Conclusions: The authors concluded that the metabolic activity of heart and lung is highly susceptible to doxorubicin and cisplatin treatment compared to 5-flurouracil and the therapeutic doses must be degraded.

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The performance of a novel amino acid multivariate index for detecting lung cancer: A case control study in Korea

Abstract: These results suggest that the amino acid multivariate index previously developed from a Japanese dataset has the potential to aid in the early detection of lung cancers of different histological types in Korean patients.

Cited by 46 publications

References 29 publications

Study of early stage non-small-cell lung cancer using Orbitrap-based global serum metabolomics

Study of early stage non-small-cell lung cancer using Orbitrap-based global serum metabolomics

Preoperative AICS (lung) abnormalities predict postoperative recurrence in patients undergoing curative resection for non-small cell lung cancer

Markers of Heart, Lung and Dorsal Aorta Damage of Mother Rats and Their Neonates Post Therapeutic Treatment with Doxorubicin, Cisplatin and 5-Flurouracil

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