Urinary N1, N12-diacetylspermine is a non-invasive marker for the diagnosis and prognosis of non-small-cell lung cancer

Takahashi, Yusuke; Sakaguchi, Koji; Horio, Hirotoshi; Hiramatsu, Kyoko; Moriya, Shigeki; Takahashi, Keiichi; Kawakita, Masao

doi:10.1038/bjc.2015.349

Cited by 40 publications

(34 citation statements)

References 28 publications

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“…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%

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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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Section: Commentarymentioning

confidence: 99%

“…Takahashi et al found that urinary DAS was an prognostic marker for NSCLC (hazard ratio of 4.652 [95% CI, 2.092-10.35]), particularly in squamous cell carcinoma [10]. Additionally, urinary DAS and N1,N8-diacetylspermidine have shown promise as diagnostic markers for breast and colorectal cancers [14].…”

Section: Commentarymentioning

confidence: 99%

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

Fahrmann¹,

Hanash²

2016

Biochem Anal Biochem

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“…At present, the prognostic factors of lung cancer therapy are widely studied (9)(10)(11)(12). A prior study revealed that the DiAcSpm/cutoff ratio (DASr) is significantly increased in NSCLC, and the DASr was revealed to be an independent negative prognostic indicator in patients with NSCLC who underwent complete resection (13). The overexpression of SRY-box 2 may serve as a positive prognostic factor in patients with stage III squamous cell lung cancer receiving adjuvant radiotherapy (14).…”

Section: Introductionmentioning

confidence: 99%

Advances in targeting the transforming growth factor β1 signaling pathway in lung cancer radiotherapy (Review)

Tang

Luo

et al. 2017

Oncol Lett

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Abstract. Lung cancer was demonstrated to be the most lethal type of malignant tumor amongst humans in the global cancer statistics of 2012. As one of the primary treatments, radiotherapy has been reported to induce remission in, and even cure, patients with lung cancer. However, the side effects of radiotherapy may prove lethal in certain patients. In past decades, the transforming growth factor β1 (TGFB1) signaling pathway has been revealed to serve multiple functions in the control of lung cancer progression and the radiotherapy response. In mammals, this signaling pathway is initiated through activation of the TGFB1 receptor complex, which signals via cytoplasmic SMAD proteins or other downstream signaling pathways. Multiple studies have demonstrated that TGFB1 serves important functions in lung cancer radiotherapy. The present study summarized and reviewed recent progress in elucidating the function of the TGFB1 signaling pathway in predicting radiation pneumonitis, as well as current strategies for targeting the TGFB1 signaling pathway in lung cancer radiotherapy, which may provide potential targets for lung cancer therapy.

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“…Although their biochemistry and physiologic role is not well understood it was shown that they are implicated in growth and development of neoplastic cells [4][5][6]. Recently, their Nacetyl derivatives detected in urine were demonstrated to be of clinical use as markers of lung cancer [7,8].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, their Nacetyl derivatives detected in urine were demonstrated to be of clinical use as markers of lung cancer [7,8]. Thus, their elevated level may serve as non-specific tumor markers, especially for the pre-cancer diagnosis [4,[9][10][11][12][13]. Their level could be also used for the monitoring efficacy of therapy [9,10].…”

Section: Introductionmentioning

confidence: 99%