J Cancer 2018; 9(9):1538-1547. doi:10.7150/jca.23973 This issue

Research Paper

Serum VEGF levels in the early diagnosis and severity assessment of non-small cell lung cancer

Yanzhen Lai1,3*, Xueping Wang1,2*, Tao Zeng1,2, Shan Xing1,2, Shuqin Dai1,2, Junye Wang1,5, Shulin Chen1,2, Xiaohui Li1,2, Ying Xie4, Yuanying Zhu1,2, Wanli Liu1,2✉

1. State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
2. Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, Guangzhou, China
3. Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China
4. Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
5. Department of thoracic surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
* Equal contributors

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Lai Y, Wang X, Zeng T, Xing S, Dai S, Wang J, Chen S, Li X, Xie Y, Zhu Y, Liu W. Serum VEGF levels in the early diagnosis and severity assessment of non-small cell lung cancer. J Cancer 2018; 9(9):1538-1547. doi:10.7150/jca.23973. Available from https://www.jcancer.org/v09p1538.htm

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Background: Effective biomarkers are essential to the differential diagnosis and severity assessment of non-small cell lung cancer (NSCLC). This study explored the use of the serum vascular endothelial growth factor (VEGF) levels as a biomarker with the aim of achieving better management of NSCLC.

Methods: Serum VEGF levels were assayed via enzyme-linked immunosorbent assay in 180 patients with NSCLC, 136 patients with benign pulmonary nodules, and 119 healthy controls. We additionally detected the serum concentration of three traditional biomarkers—carcinoembryonic antigen (CEA), cancer antigen (CA)-125, and cytokeratin 19 fragments (Cyfra 21-1)—to comparatively evaluate the efficiency and diagnostic value of VEGF in patients with NSCLC. We further evaluated the relationship between serum VEGF levels and clinicopathologic parameters. VEGF levels were compared between pro- and post-surgical patients using the Wilcoxon matched-pairs signed-rank test. DNA was isolated from the primary tumors. EGFR mutations were detected by Scorpions amplification refractory mutation system (ARMS).

Results: Patients with NSCLC had significantly higher serum concentration of VEGF, compared to those with benign pulmonary nodules and healthy controls (P <0.0001). As a diagnostic biomarker of NSCLC, VEGF had area under the curve values of 0.824 and 0.839, sensitivities of 75.0% and 75.0%, and specificities of 93.3% and 95.6% when compared with healthy people and patients with benign pulmonary nodules, respectively; notably, these values were greater than those of CA125, Cyfra 21-1 and CEA. Furthermore, a model in which VEGF was combined with CEA, CA125, and Cyfra 21-1 was more effective for NSCLC diagnosis than VEGF alone (sensitivity, 85.0% and 84.4; specificity, 90.0% and 91.9% vs. healthy controls and patients with benign pulmonary nodules, respectively). When use to identify early-stage NSCLC, VEGF showed a better diagnostic efficacy than other biomarkers. The pro-surgical VEGF levels were significantly higher than those measured 25-30 days after surgery. Moreover, VEGF concentration differed significantly among cases according to TNM stages and malignant grades (P <0.0001). EGFR mutations and the size of benign pulmonary nodules did not affect the level of serum VEGF significantly.

Conclusion: The serum VEGF levels exhibited relatively high sensitivity and specificity for NSCLC, and may therefore be a useful diagnostic biomarker. Furthermore, the serum VEGF levels could be used to assess prognosis and curative effects.

Keywords: Non-small cell lung cancer, biomarker, vascular endothelial growth factor, benign pulmonary nodules