Decreased Pretherapy Serum Apolipoprotein A-I is Associated with Extent of Metastasis and Poor Prognosis of Non-small-cell Lung Cancer

Background: Apolipoprotein A-I (ApoA-I), which recently attracted great attention as an important protein related to the increasing risk of various cancers, is a factor closely related to metabolic diseases such as ardiovascular diseases and atherosclerosis. However, the diagnostic and prognostic value of pretherapy serum ApoA-I levels in non-small-cell lung cancer (NSCLC) patients is still not very clear.

Methods: In 325 NSCLC patients and 312 healthy controls, pretherapy serum ApoA-I was measured by turbidimetric immunoassay. The association of serum ApoA-I levels with the clinicopathologic characteristics and clinical outcomes of NSCLC patients was analyzed. Receiver-operating characteristic (ROC) curve analysis and univariate and multivariate Cox regression analyses were used to assess the diagnostic and prognostic significance of serum ApoA-I levels.

Results: Serum ApoA-I levels were obviously decreased in NSCLC patients compared with healthy controls (1.22±0.27 vs 1.46±0.22 g/L, <0.0001). Pretherapy serum ApoA-I levels were significantly decreased in the NSCLC patients with increased pretherapy C-reactive protein levels (=0.046), lower albumin serum level (=0.040), advanced TNM stage (=0.004), poorer Eastern Cooperative Oncology Group PS: performance status scores (=0.007), and more than two sites of distant metastasis (<0.0001). ROC curve showed the optimal cut-off for ApoA-I was 1.26 g/L (Area under ROC curve=0.69, 95% CI=0.54-0.65) with a specificity of 0.75 and a sensitivity of 0.59. The whole cohort was divided into two groups: low ApoA-I levels group (ApoA-I ≤1.26 g/L) consisted of 193 (59.4%) patients and high ApoA-I levels group (ApoA-I >1.26 g/L) consisted of 132 (40.6%) patients. The median survival time of low and high ApoA-I levels patients were 16.45 and 20.90 months, respectively, which indicated a statistically significant difference ( =0.609, <0.0001) between the two groups. The multivariate analysis results showed that CRP levels (HR=1.273, =0.038), ApoA-I levels (HR=0.761, =0.030), Eastern Cooperative Oncology Group performance status (HR=1.486, =0.016), and extent of metastasis (HR=1.394, =0.009) were significant independent predictors of favorable overall survival.

Conclusion: A decreased level of pretherapy ApoA-I was associated with a worse survival in patients with NSCLC. Serum ApoA-I measurement before initial treatment may be a novel and routine biomarker to evaluate for metastasis and predict prognosis for NSCLC patients in daily clinical practice.