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Multicenter Study
. 2015 Nov 17;113(10):1493-501.
doi: 10.1038/bjc.2015.349. Epub 2015 Oct 27.

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

Yusuke Takahashi  1   2 , Koji Sakaguchi  1   3 , Hirotoshi Horio  1 , Kyoko Hiramatsu  4 , Shunsuke Moriya  4 , Keiichi Takahashi  1 , Masao Kawakita  4
Affiliations
Multicenter Study

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

Yusuke Takahashi et al. Br J Cancer. .

Abstract

Background: Early detection of non-small-cell lung cancer (NSCLC) and accurate prognostic risk assessment could improve patient outcome. We examined the significance of urinary N(1), N(12)-diacetylspermine (DiAcSpm) in the detection and prognostic stratification of NSCLC patients.

Methods: A DiAcSpm/cutoff ratio (DASr) was established for 260 NSCLC patients, 99 benign lung disease patients, and 140 healthy volunteers, using colloidal gold aggregation methods. The DASr was compared between patients and healthy controls, and the prognostic significance of DASr was examined.

Results: The median urinary DASr of NSCLC patients was significantly higher than that of healthy controls (0.810 vs 0.534, P<0.001). The DASr was higher in squamous cell carcinoma (SqCC) patients than in adenocarcinoma patients (1.18 vs 0.756, respectively, P=0.039). An increased urinary DASr value was significantly associated with pathological stage, other histological invasive factors and unfavourable outcomes in patients with completely resected NSCLC. Multivariate Cox regression analysis showed that increased urinary DASr was an independent prognostic factor (hazard ratio=4.652, 95% confidence interval (CI), 2.092-10.35; P<0.001).

Conclusions: Urinary DASr was significantly increased in NSCLC, especially in SqCC. Urinary DASr was an independent poor prognostic indicator in patients with completely resected NSCLC. The DASr could be a useful biomarker for detecting malignancies and predicting prognosis.

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Figures

Figure 1
Figure 1
Comparison of urinary DASr level according to various status. (A) A box plot showing the urinary DASr levels in healthy controls and patients with non-small-cell lung cancer classified according to tumour histology. *P<0.05 vs healthy controls, **P<0.05 between the indicated groups. (B) A box plot showing the urinary DASr in healthy controls and patients with non-small-cell lung cancer classified according to clinical staging. *P<0.05 vs healthy controls, **P<0.05 between the indicated groups. (C) A box plot showing the urinary DASr in healthy controls and patients with benign lung or pleural diseases. *P<0.05 vs healthy controls, **P<0.05 between the indicated groups. (D) A box plot showing the urinary DASr in patients with non-small-cell lung cancer classified according to smoking status. A comparison using the Mann–Whitney U-test demonstrated no significant differences (P=0.950).
Figure 2
Figure 2
A receiver-operating characteristics (ROC) curve to test the predictive ability of urinary DASr levels for the diagnosis of non-small-cell lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma. The AUC for the diagnosis of non-small-cell lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma were 0.750, 0.711, and 0.873, respectively.
Figure 3
Figure 3
Survival curves according to urinary DASr level. (A) Kaplan–Meier overall survival curves for patients with resected NSCLC classified into two groups according to their urinary DASr levels. (B) Kaplan–Meier recurrence-free survival curves for patients with resected NSCLC classified into two groups according to their urinary DASr levels.
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