Significant correlation between urinary N(1), N(12)-diacetylspermine and tumor invasiveness in patients with clinical stage IA non-small cell lung cancer

Yusuke Takahashi, Hirotoshi Horio, Koji Sakaguchi, Kyoko Hiramatsu, Masao Kawakita

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

BACKGROUND: To select optimal candidates for limited lung resection, it is necessary to accurately differentiate the non-invasive tumors from other small-sized lung cancer. Urinary N(1), N(12)-diacetylspermine (DiAcSpm) has been reported to be a useful tumor marker for various cancers. We aimed to examine the correlation between preoperative urinary DiAcSpm levels and specific clinicopathological characteristics such as the histological tumor invasiveness in patients with clinical stage IA non-small cell lung cancer (NSCLC).

METHODS: We defined non-invasive tumors as NSCLC showing no vascular invasion, lymphatic permeation, pleural invasion, or lymph node metastasis. Preoperative urine samples were obtained from 516 consecutive patients with NSCLC resected at our institution between April 2008 and January 2013. Urinary DiAcSpm values were determined for all preoperative urine samples using the colloid gold aggregation procedure. Among these patients, 171 patients with clinical stage IA NSCLC met the criteria of our study cohort. Finally, we investigated the correlation between non-invasive tumor and urinary DiAcSpm levels.

RESULTS: The median urine DiAcSpm for males was 147.2 nmol/g creatinine and 161.8 nmol/g creatinine in females. These median values were set as the cut-off values for each gender. Patients with higher urinary DiAcSpm levels frequently had significantly elevated serum CEA (p = 0.023) and greater lymph node metastasis (p = 0.048), lymphatic permeation (p = 0.046), and vascular invasion (p = 0.010). Compared with patients with non-invasive tumors, patients with invasive tumors had a tumor size >2.0 cm (p = 0.001), serum CEA >5.0 mg/dL (p < 0.001), high urinary DiAcSpm (p = 0.002), and a tumor disappearance rate (TDR) <0.75 (p < 0.001). Multivariate analysis revealed that a tumor size < 2.0 cm (RR = 2.901, 95% CI; 1.372-6.136, p = 0.005), high urinary DiAcSpm (RR = 3.374, 95% CI; 1.547-7.361, p = 0.002), and TDR < 0.75 (RR = 4.673, 95% CI; 2.178-10.027, p < 0.001) were independent predictors for invasive tumors.

CONCLUSIONS: We successfully showed that there was a significant correlation between urinary DiAcSpm levels and pathological tumor invasiveness in patients with clinical stage IA NSCLC. Further research would elucidate the clinical usefulness of DiAcSpm levels as a predictor of tumor invasiveness.

Original languageEnglish
Number of pages1
JournalBMC Cancer
Volume15
DOIs
Publication statusPublished - 2015 Jan 1
Externally publishedYes

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Non-Small Cell Lung Carcinoma
Neoplasms
Urine
N',N''-diacetylspermine
Blood Vessels
Creatinine
Lymph Nodes
Neoplasm Metastasis
Gold Colloid
Tumor Biomarkers
Serum
Lung Neoplasms
Cohort Studies
Multivariate Analysis

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

Cite this

Significant correlation between urinary N(1), N(12)-diacetylspermine and tumor invasiveness in patients with clinical stage IA non-small cell lung cancer. / Takahashi, Yusuke; Horio, Hirotoshi; Sakaguchi, Koji; Hiramatsu, Kyoko; Kawakita, Masao.

In: BMC Cancer, Vol. 15, 01.01.2015.

Research output: Contribution to journalArticle

Takahashi, Yusuke ; Horio, Hirotoshi ; Sakaguchi, Koji ; Hiramatsu, Kyoko ; Kawakita, Masao. / Significant correlation between urinary N(1), N(12)-diacetylspermine and tumor invasiveness in patients with clinical stage IA non-small cell lung cancer. In: BMC Cancer. 2015 ; Vol. 15.
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title = "Significant correlation between urinary N(1), N(12)-diacetylspermine and tumor invasiveness in patients with clinical stage IA non-small cell lung cancer",
abstract = "BACKGROUND: To select optimal candidates for limited lung resection, it is necessary to accurately differentiate the non-invasive tumors from other small-sized lung cancer. Urinary N(1), N(12)-diacetylspermine (DiAcSpm) has been reported to be a useful tumor marker for various cancers. We aimed to examine the correlation between preoperative urinary DiAcSpm levels and specific clinicopathological characteristics such as the histological tumor invasiveness in patients with clinical stage IA non-small cell lung cancer (NSCLC).METHODS: We defined non-invasive tumors as NSCLC showing no vascular invasion, lymphatic permeation, pleural invasion, or lymph node metastasis. Preoperative urine samples were obtained from 516 consecutive patients with NSCLC resected at our institution between April 2008 and January 2013. Urinary DiAcSpm values were determined for all preoperative urine samples using the colloid gold aggregation procedure. Among these patients, 171 patients with clinical stage IA NSCLC met the criteria of our study cohort. Finally, we investigated the correlation between non-invasive tumor and urinary DiAcSpm levels.RESULTS: The median urine DiAcSpm for males was 147.2 nmol/g creatinine and 161.8 nmol/g creatinine in females. These median values were set as the cut-off values for each gender. Patients with higher urinary DiAcSpm levels frequently had significantly elevated serum CEA (p = 0.023) and greater lymph node metastasis (p = 0.048), lymphatic permeation (p = 0.046), and vascular invasion (p = 0.010). Compared with patients with non-invasive tumors, patients with invasive tumors had a tumor size >2.0 cm (p = 0.001), serum CEA >5.0 mg/dL (p < 0.001), high urinary DiAcSpm (p = 0.002), and a tumor disappearance rate (TDR) <0.75 (p < 0.001). Multivariate analysis revealed that a tumor size < 2.0 cm (RR = 2.901, 95{\%} CI; 1.372-6.136, p = 0.005), high urinary DiAcSpm (RR = 3.374, 95{\%} CI; 1.547-7.361, p = 0.002), and TDR < 0.75 (RR = 4.673, 95{\%} CI; 2.178-10.027, p < 0.001) were independent predictors for invasive tumors.CONCLUSIONS: We successfully showed that there was a significant correlation between urinary DiAcSpm levels and pathological tumor invasiveness in patients with clinical stage IA NSCLC. Further research would elucidate the clinical usefulness of DiAcSpm levels as a predictor of tumor invasiveness.",
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T1 - Significant correlation between urinary N(1), N(12)-diacetylspermine and tumor invasiveness in patients with clinical stage IA non-small cell lung cancer

AU - Takahashi, Yusuke

AU - Horio, Hirotoshi

AU - Sakaguchi, Koji

AU - Hiramatsu, Kyoko

AU - Kawakita, Masao

PY - 2015/1/1

Y1 - 2015/1/1

N2 - BACKGROUND: To select optimal candidates for limited lung resection, it is necessary to accurately differentiate the non-invasive tumors from other small-sized lung cancer. Urinary N(1), N(12)-diacetylspermine (DiAcSpm) has been reported to be a useful tumor marker for various cancers. We aimed to examine the correlation between preoperative urinary DiAcSpm levels and specific clinicopathological characteristics such as the histological tumor invasiveness in patients with clinical stage IA non-small cell lung cancer (NSCLC).METHODS: We defined non-invasive tumors as NSCLC showing no vascular invasion, lymphatic permeation, pleural invasion, or lymph node metastasis. Preoperative urine samples were obtained from 516 consecutive patients with NSCLC resected at our institution between April 2008 and January 2013. Urinary DiAcSpm values were determined for all preoperative urine samples using the colloid gold aggregation procedure. Among these patients, 171 patients with clinical stage IA NSCLC met the criteria of our study cohort. Finally, we investigated the correlation between non-invasive tumor and urinary DiAcSpm levels.RESULTS: The median urine DiAcSpm for males was 147.2 nmol/g creatinine and 161.8 nmol/g creatinine in females. These median values were set as the cut-off values for each gender. Patients with higher urinary DiAcSpm levels frequently had significantly elevated serum CEA (p = 0.023) and greater lymph node metastasis (p = 0.048), lymphatic permeation (p = 0.046), and vascular invasion (p = 0.010). Compared with patients with non-invasive tumors, patients with invasive tumors had a tumor size >2.0 cm (p = 0.001), serum CEA >5.0 mg/dL (p < 0.001), high urinary DiAcSpm (p = 0.002), and a tumor disappearance rate (TDR) <0.75 (p < 0.001). Multivariate analysis revealed that a tumor size < 2.0 cm (RR = 2.901, 95% CI; 1.372-6.136, p = 0.005), high urinary DiAcSpm (RR = 3.374, 95% CI; 1.547-7.361, p = 0.002), and TDR < 0.75 (RR = 4.673, 95% CI; 2.178-10.027, p < 0.001) were independent predictors for invasive tumors.CONCLUSIONS: We successfully showed that there was a significant correlation between urinary DiAcSpm levels and pathological tumor invasiveness in patients with clinical stage IA NSCLC. Further research would elucidate the clinical usefulness of DiAcSpm levels as a predictor of tumor invasiveness.

AB - BACKGROUND: To select optimal candidates for limited lung resection, it is necessary to accurately differentiate the non-invasive tumors from other small-sized lung cancer. Urinary N(1), N(12)-diacetylspermine (DiAcSpm) has been reported to be a useful tumor marker for various cancers. We aimed to examine the correlation between preoperative urinary DiAcSpm levels and specific clinicopathological characteristics such as the histological tumor invasiveness in patients with clinical stage IA non-small cell lung cancer (NSCLC).METHODS: We defined non-invasive tumors as NSCLC showing no vascular invasion, lymphatic permeation, pleural invasion, or lymph node metastasis. Preoperative urine samples were obtained from 516 consecutive patients with NSCLC resected at our institution between April 2008 and January 2013. Urinary DiAcSpm values were determined for all preoperative urine samples using the colloid gold aggregation procedure. Among these patients, 171 patients with clinical stage IA NSCLC met the criteria of our study cohort. Finally, we investigated the correlation between non-invasive tumor and urinary DiAcSpm levels.RESULTS: The median urine DiAcSpm for males was 147.2 nmol/g creatinine and 161.8 nmol/g creatinine in females. These median values were set as the cut-off values for each gender. Patients with higher urinary DiAcSpm levels frequently had significantly elevated serum CEA (p = 0.023) and greater lymph node metastasis (p = 0.048), lymphatic permeation (p = 0.046), and vascular invasion (p = 0.010). Compared with patients with non-invasive tumors, patients with invasive tumors had a tumor size >2.0 cm (p = 0.001), serum CEA >5.0 mg/dL (p < 0.001), high urinary DiAcSpm (p = 0.002), and a tumor disappearance rate (TDR) <0.75 (p < 0.001). Multivariate analysis revealed that a tumor size < 2.0 cm (RR = 2.901, 95% CI; 1.372-6.136, p = 0.005), high urinary DiAcSpm (RR = 3.374, 95% CI; 1.547-7.361, p = 0.002), and TDR < 0.75 (RR = 4.673, 95% CI; 2.178-10.027, p < 0.001) were independent predictors for invasive tumors.CONCLUSIONS: We successfully showed that there was a significant correlation between urinary DiAcSpm levels and pathological tumor invasiveness in patients with clinical stage IA NSCLC. Further research would elucidate the clinical usefulness of DiAcSpm levels as a predictor of tumor invasiveness.

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