Systemic Metabolomic Changes in Blood Samples of Lung Cancer Patients Identified by Gas Chromatography  Time-of-Flight Mass Spectrometry

Miyamoto, Suzanne; Taylor, Sandra L.; Barupal, Dinesh Kumar; Taguchi, Ayumu; Wohlgemuth, Gert; Wikoff, William R.; Yoneda, Ken Y.; Gandara, David R.; Hanash, Samir M.; Kim, Kyoungmi; Fiehn, Oliver

doi:10.3390/metabo5020192

Cited by 73 publications

(61 citation statements)

References 47 publications

(60 reference statements)

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“…Therefore, abnormal metabolism of plasma directly affects the quality of sperm. Previous studies have shown that plasma has a strong association with many complex diseases including a variety of cancers, [17][18][19] diabetes, 20 metabolic syndrome 21 and sepsis-induced acute lung injury. 22 Therefore, plasma is suitable for the systematic analysis of MI.…”

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confidence: 99%

Metabolic profiling putatively identifies plasma biomarkers of male infertility using UPLC-ESI-IT-TOFMS

Zeng

Zhang

et al. 2018

RSC Adv.

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Male infertility has become a global health problem. Currently, the diagnosis of male infertility depends on the results of semen quality or requires invasive surgical intervention. The process is complex and timeconsuming. Metabolomics is an emerging platform with unique advantages in disease diagnosis and pathological mechanism research. In this study, ultra-performance liquid chromatography-electrospray ionization-ion trap-time of flight mass spectrometry (UPLC-ESI-IT-TOFMS) combined with chemometrics methods was used to discover potential biomarkers of male infertility based on nontargeted plasma metabolomics. Plasma samples from healthy controls (HC, n ¼ 43) and various types of infertile patients, i.e., patients having oligozoospermia (OS, n ¼ 36), asthenospermia (AS, n ¼ 56) and erectile dysfunction (ED, n ¼ 45) were analyzed by UPLC-ESI-IT-TOFMS. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed. The results of OPLS-DA showed that HCs could be discriminated from infertile patients including OS (R 2 ¼ 0.903,Some potential biomarkers were successfully discovered by variable selection methods and variable important in the projection (VIP) in combination with the T-test. Statistical significance was set at p < 0.05; the Benjamini-Hochberg false discovery rate was used to reduce type 1 errors resulting from multiple comparisons. The identified biomarkers were associated with energy consumption, hormone regulation and antioxidant defenses in spermatogenesis. To elucidate the pathophysiology of male infertility, relative metabolic pathways were studied. It was found that male infertility is closely related to disturbed phospholipid metabolism, amino acid metabolism, steroid hormone biosynthesis metabolism, metabolism of fatty acids and products of carnitine acylation, and purine and pyrimidine metabolisms. Plasma metabolomics provides a novel strategy for the diagnosis of male infertility and offers a new insight to study pathogenesis mechanism.

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confidence: 99%

Metabolic profiling putatively identifies plasma biomarkers of male infertility using UPLC-ESI-IT-TOFMS

Zeng

Zhang

et al. 2018

RSC Adv.

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“…Shifts in tryptophan metabolism through the kynurenine pathway have been previously reported in cancer, asthma, dengue infection, Alzheimer disease, AIDS, Huntington disease, schizophrenia and depression [9][10][11][12][13][14] . There are 3 known enzymes that oxidize tryptophan in the kynurenine pathway: tryptophan 2,3-dioxygenase (TDO), the predominant enzyme indoleamine 2,3-dioxygenase 1 (IDO-1) or IDO-2 [15,16] .…”

Section: Discussionmentioning

confidence: 99%

Activation of Tryptophan and Phenylalanine Catabolism in the Remission Phase of Allergic Contact Dermatitis: A Pilot Study

Zinkevičienė

Kainov

Girkontaitė

et al. 2016

Int Arch Allergy Immunol

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Background: Allergic contact dermatitis (ACD) is an inflammatory skin disease caused by repeated skin exposure to contact allergens. The severity and duration of this disease are associated with many different factors. Some of these factors may represent markers for monitoring disease activity and the individual response to an intervention. Methods: We used a targeted metabolomics approach to find such factors in the serum of individuals with ACD. Metabolomics profiles were examined and compared in the acute phase of the disease and also in the absence of disease activity. Results: Our study identified a significant remission phase of ACD-associated systemic biochemical shifts in 2 metabolic pathways: tryptophan-kynurenine and phenylalanine-tyrosine. Conclusions: Although the responsible mechanisms are unclear, these results suggest that the remission phase of ACD is linked to tryptophan metabolism via kynurenine and phenylalanine-tyrosine pathways. However, further replication studies with a larger number of subjects and their subgroups are necessary to validate our results. These studies may provide a new perspective with which to understand the mechanism of and find potential biomarkers of ACD, as well as a new reference for personalized treatment.

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Section: Commentarymentioning

confidence: 99%

“…As a result, interest in the application of metabolomics to identify key metabolic differences related to pathological conditions has expanded. Indeed, metabolomics has been explored to gain insights into the pathophysiology of cancer, develop methods predictive of disease onset, and reveal new biomarkers relevant to disease diagnosis and prognosis [4][5][6] [ [10][11][12].…”

Section: Commentarymentioning

confidence: 99%

“…Such knowledge is critical to assessment of the specificity of the marker. For instance, we have previously identified other circulating metabolites, independent from DAS, which distinguish subjects with NSCLC relative to control including reductions in the immune-regulatory metabolite tryptophan and elevations in maltose and glutamate [11].Serum glutamate has exhibited good performance in discriminating early stage (IA/IB) NSCLC adenocarcinoma from control with an accuracy of 61.3% and 74.4% in the discovery and validation test sets, respectively [4]. Multiplex assays of 4 serum-based metabolite classifiers consisting of xylose, glutamate, aspartate and one unknown [Bin_225393] yielded accuracies of 66.9% and 72.7% in the discovery and test sets, respectively [4].…”

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confidence: 99%

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N1,N12-Diacetylspermine as a Blood Based Lung Cancer Biomarker

Fahrmann¹,

Hanash²

2016

Biochem Anal Biochem

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It is becoming well recognized that metabolic perturbations are inherent hallmarks of tumorigenesis [1,2]. Metabolites represent the functional products of cellular processes, which are highly responsive to both pathological and environmental stimuli. As such, metabolites are the closest representation of an individual's current physiological state. Therefore, exploration of metabolic alterations in the context of disease pathophysiology, most notably cancer, holds great promise and considerable clinical value. This field of research has benefited from technological advances in mass spectrometry and ultraviolet-visible spectroscopic analyses that have enabled comprehensive metabolomic analyses of diverse arrays of metabolites, polyphenols and lipids in a variety of biological matrices with substantial robustness and sensitivity [3][4][5][6][7][8][9]. As a result, interest in the application of metabolomics to identify key metabolic differences related to pathological conditions has expanded. Indeed, metabolomics has been explored to gain insights into the pathophysiology of cancer, develop methods predictive of disease onset, and reveal new biomarkers relevant to disease diagnosis and prognosis [4-6] [10-12].The application of metabolomics to the discovery of blood-based biomarker in cancer has substantial potential clinical relevance. Recently, we have identified the polyamine end-product N1, N12-diacetylspermine (DAS) as a novel pre-diagnostic serum biomarker for non-small cell lung cancer (NSCLC) [6]. In this study, DAS alone yielded an AUC of 0.610 and AUC 0.710 for sera collected 6 to 12 months and 0 to 6 months before onset of symptoms and diagnosis, respectively, in the discovery set. These findings were subsequently confirmed in an independent and blinded validation set [6]. Single markers are unlikely to exhibit sufficient performance to be fully informative of disease status. Therefore in our study we examined the performance of DAS in combination with another marker Pro-SFTPB, which we previously validated as a blood based marker for NSCLC [13]. The combination of DAS and Pro-SFTPB resulted in improved performance compared to either alone (Overall AUCs of 0.732, 0.650 and 0.699 in the validation set for Pro-SFTPB + DAS, DAS only and Pro-SFTPB only, respectively) [6]. This study highlights the potential contributions of metabolomics to the discovery of biomarkers that inform about disease risk before the onset of symptoms and, importantly, illustrates the value of DAS as a complementary non-invasive biomarker. While the latter findings implicate that DAS is not specific to lung cancer, it does highlight conserved metabolic dysregulation of polyamine biosynthesis, which is strongly associated with tumorigenesis [15,16]. However, one caveat that must always be considered is whether serum or urinary DAS differs between malignant and benign tumors. This is particularly relevant in lung cancer as screening methodologies have been largely hindered by high false positive rates, a consequence of the low preval...

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Systemic Metabolomic Changes in Blood Samples of Lung Cancer Patients Identified by Gas Chromatography Time-of-Flight Mass Spectrometry

Cited by 73 publications

References 47 publications

Metabolic profiling putatively identifies plasma biomarkers of male infertility using UPLC-ESI-IT-TOFMS

Metabolic profiling putatively identifies plasma biomarkers of male infertility using UPLC-ESI-IT-TOFMS

Activation of Tryptophan and Phenylalanine Catabolism in the Remission Phase of Allergic Contact Dermatitis: A Pilot Study

N1,N12-Diacetylspermine as a Blood Based Lung Cancer Biomarker

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