Establishment of a biomarker model for predicting bone metastasis in resected stage III non-small cell lung cancer

Zhen Zhou,Qing-Quan Luo,Lan Shen,Shun Lu,Zhi-Wei Chen,Xiao-Hua Yang,Xing-Hao Ai

doi:10.1186/1756-9966-31-34

Zhen Zhou, Qing-Quan Luo + Show 5 more

Open Access

https://doi.org/10.1186/1756-9966-31-34

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Abstract

BackgroundThis study was designed to establish a biomarker risk model for predicting bone metastasis in stage III non-small cell lung cancer (NSCLC).MethodsThe model consists of 105 cases of stage III NSCLC, who were treated and followed up. The patients were divided into bone metastasis group (n = 45) and non-bone metastasis group (other visceral metastasis and those without recurrence) (n = 60). Tissue microarrays were constructed for immunohistochemical study of 10 molecular markers associated with bone metastasis, based on which a model was established via logistic regression analysis for predicting the risk of bone metastases. The model was prospectively validated in another 40 patients with stage III NSCLC.ResultsThe molecular model for predicting bone metastasis was logit (P) = − 2.538 + 2.808 CXCR4 +1.629 BSP +0.846 OPN-2.939 BMP4. ROC test showed that when P ≥ 0.408, the sensitivity was up to 71% and specificity of 70%. Model validation in the 40 cases in clinical trial (NCT 01124253) demonstrated that the prediction sensitivity of the model was 85.7%, specificity 66.7%, Kappa: 0.618, with a high degree of consistency.ConclusionThe molecular model combining CXCR4, BSP, OPN and BMP4 could help predict the risk of bone metastasis in stage IIIa and IIIb resected NSCLC.

Highlights

Tumor cells homing to form bone metastases is common in non-small cell lung cancer (NSCLC), just like what is seen in breast, prostate and thyroid cancers
The molecular and cellular mechanisms leading to the development of bone metastasis in NSCLC remain unclear, in this study, we investigated the current understanding of bone metastasis in NSCLC
Pathologic stage statistically significant difference was found between bone metastasis group and non-bone metastasis group in terms of clinical and pathological factors (Table 1)

Summary

Introduction

Tumor cells homing to form bone metastases is common in non-small cell lung cancer (NSCLC), just like what is seen in breast, prostate and thyroid cancers. Some patients may experience bone metastasis many years after surgery of the primary tumor. The high morbidity and significantly increased risk of fractures associated with bone metastasis seriously affect patients' quality of life. About 36% of all lung cancers and and 54.5% of stage II-IIIA NSCLC showed postoperative recurrence or metastasis [1]. Many lung cancer patients expect new and more sensitive resected stage III NSCLC to screen the patients at high risk of bone metastasis for early intervention. This study was designed to establish a biomarker risk model for predicting bone metastasis in stage III non-small cell lung cancer (NSCLC)

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Conclusion