The potential prognostic roles of biomarker expression in peripheral blood for non-small cell lung cancer

• Main Authors: Yi-Ying Wu, 吳宜穎
• Other Authors: Tsu-Yi Chao
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/13248629839738194441

博士 === 國防醫學院 === 生命科學研究所 === 105 === Background Lung cancer is a heterogeneous disease with varied outcomes, and metastasis to various sites. Molecular markers are eagerly sought to predict patient’s treatment response or outcome. Previous studies used frozen biopsy tissues to identify crucial genes as prognostic markers. Also diagnosis and follow-up of bone metastasis (BMet) in non-small cell lung cancer (NSCLC) patients usually rely on symptoms and image studies. Therefore, we tried to explore the prognostic value of peripheral blood (PB) signatures, including serum markers and genetic alteration in advanced NSCLC patients. Methods Peripheral bloods were obtained. Serum and PB mononuclear cells (PBMC) fractions from patients with advanced NSCLC were extracted and applied for serum marker, and gene analysis. First part, immunoassay using a Tartrate-resistant acid phosphatase (TRACP) -specific monoclonal antibody, 14G6, was used to measure the serum TRACP5b activity. Second part, RNA was extracted, cDNA was synthesis and real-time PCR was checked for expression profiling. Eight genes, DUSP6, MMD, CPEB4, RNF4, STAT2, NF1, IRF4 and ZNF264, were selected according to previous cohort study. Proportional hazard (PH) models were constructed to evaluate the association of the 8 expressing genes and multiple clinical factors including gender, smoking status and Charlson comorbidity index (CCI), with overall survival. Results Total of 141 patients with advanced NSCLC were enrolled separated in our 2 parts of studies. First, we found lung cancer patient with bone metastasis had higher level of TRACP5b. TRACP5b activity declined in patients who responded to treatment (p=0.047), and it elevated in patients who developed new BMet (p=0.05). We found that TRACP5b activity is a good marker for lung cancer diagnosis and monitoring treatment effect. Second part of our study, we evaluated gene expression of PBMC. The PH model was checked, and found two significant survival-associated genes, CPEB4 and IRF4, could help to predict overall survival of advanced stage NSCLC patients (HR＝0.48, p<0.0001). Adding multiple clinical factors further improved the prediction power of prognosis (HR＝0.33, p<0.0001). Conclusions Serum and molecular signatures of PB both could be used to monitor advanced NSCLC patients’ prognosis and treatment response. Further prospective, interventional clinical trials should be carried out to test if gene profiling also predicts resistance to chemotherapy and target therapy.