Research Article: Elevated N-telopeptide as a potential diagnostic marker for bone metastasis in lung cancer: A meta-analysis

Date Published: November 28, 2017

Publisher: Public Library of Science

Author(s): Boxuan Liu, Yun Zhao, Jingyan Yuan, Lizhong Zeng, Ruiying Sun, Xia Meng, Shuanying Yang, Sumitra Deb.


Growing evidence indicates that the cross-linked N-telopeptide of type I collagen (NTx) is likely to be involved in the development of bone metastasis among lung cancer patients. We perform a meta-analysis to disclose the correlation between bone metastasis and NTx and also to evaluate its value in diagnosis of bone metastasis (BM) in lung cancer.

Electronic databases were searched and calculated the weighted mean difference (WMD) with 95% confidence interval (CI) to assess the expression difference of NTx between BM+ and BM- lung cancer patients. Moreover, we conducted a sensitivity and specificity test and drew a summary receiver operating characteristic curve (SROC) to assess the diagnostic value of NTx in discerning bone metastasis.

A total of eleven studies with 1108 individuals were included in this analysis. The results showed an increased NTx was correlated with the incidence of lung cancer (P < 0.001). The overall sensitivity and specificity of serum NTx (sNTx) for discerning bone metastasis was 0.74 (95% CI = 0.67 to 0.79) and 0.85 (95% CI = 0.80 to 0.89), respectively. As for urine NTx (uNTx) the pooled sensitivity and specificity was 0.77(95% CI = 0.67 to 0.86) and 0.81(95% CI = 0.76 to 0.86). The area under the SROC curve was 0.8889(SE = 0.0255) and 0.8655(SE = 0.0254) for sNTx and uNTx respectively. The elevation of NTx in lung cancer was positively related with the development and progression of bone metastasis. A higher specificity over sensitivity of NTx suggested that it is a more accurate biomarker to distinguish patients without bone metastasis. Regarding SROC curve, sNTx may be a better choice.

Partial Text

Lung cancer has been the most common malignancy for several decades with an estimated 1.8million new cases annually and resulted in one cancer death in five (1.59 million deaths,19.4% of total)[1]. A majority of lung cancer patients are in advanced stage at the time of diagnosis and bone is tended to be the most common affected site with a rough rate of 30% to 60%[2]. The occurrence of skeletal-related events (SREs) such as pathologic fracture and hypercalcemia[3]followed by bone metastasis (BM) will not only result in a poor quality of life but also can be costly. Nowadays, the diagnosis of bone metastasis in cancer patients relies predominantly on imaging techniques, such as bone scintigraphy which often has a high sensitivity but lacks specificity[4], computerized tomography (CT), magnetic resonance imaging (MRI) or18F-fluorodeoxyglucose positron emission tomography (F-18 FDG-PET). Although these techniques have been proved to be useful diagnostic tools, their limitations on early diagnosis or time-to-time monitoring cannot be ignored. Thus, these weaknesses of current methodology lead to a need for establishing supplementary diagnostic tools.

So far, lung cancer has become the leading cause of cancer-related deaths worldwide and the 5-year survival rate is only slightly above 10%[1]. A previous study shows that in the clinical course of lung cancer, a third of all patients will suffer from bone metastasis and the SREs significantly affects clinical outcome with a median survival time of 4.1 months[21]. NTx, a biochemical marker of bone metabolism, is considered to be elevated during bone metastasis because it reflects the ongoing rate of bone osteolysis. Thus the elevation of NTx has been further discussed as a diagnostic biomarker in solid tumors [22–24]. A previous meta-analysis[7] has demonstrated an elevation of NTx in bone metastasis patients, however, it fails to calculate the sensitivity and specificity of NTx in the diagnosis of bone metastasis which would be an important data for further clinical trial and application. Besides, the patients included have different kinds of tumor which may result in bias when applied in lung cancer patients. Moreover, serum and urine are the two sources of specimen in detecting NTx but the study has failed to evaluate urine NTx and its correlation with serum NTx in terms of efficacy. Therefore, we review the literature so as to make a more comprehensive analysis on the role of NTx as a diagnostic biomarker.