Int J Biol Sci 2019; 15(9):1977-1992. doi:10.7150/ijbs.36284 This issue Cite

Research Paper

Development and Validation of Tumor-educated Blood Platelets Integrin Alpha 2b (ITGA2B) RNA for Diagnosis and Prognosis of Non-small-cell Lung Cancer through RNA-seq

Shan Xing1#, Tao Zeng2#, Ning Xue3#, Yi He1, Yan-zhen Lai1, Hui-lan Li1, Qi Huang1, Shu-lin Chen1✉, Wan-li Liu1✉

1. Department of Clinical Laboratory, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
2. Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510060, P. R. China
3. Department of Clinical Laboratory, Affiliated Tumor Hospital of Zhengzhou University, Henan Tumor Hospital, Zhengzhou 450100, P. R. China
# Equal contributors

Citation:
Xing S, Zeng T, Xue N, He Y, Lai Yz, Li Hl, Huang Q, Chen Sl, Liu Wl. Development and Validation of Tumor-educated Blood Platelets Integrin Alpha 2b (ITGA2B) RNA for Diagnosis and Prognosis of Non-small-cell Lung Cancer through RNA-seq. Int J Biol Sci 2019; 15(9):1977-1992. doi:10.7150/ijbs.36284. https://www.ijbs.com/v15p1977.htm
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Abstract

Graphic abstract

Background: Currently, there are no molecular biomarkers for the early detection of non-small-cell lung cancer (NSCLC). This study focused on identifying RNAs found on tumor-educated blood platelets (TEPs) for detecting stage I NSCLC.

Methods: Platelet RNAs, isolated from the blood of 9 patients with NSCLC (stages I and II) and 8 healthy controls, were analyzed using RNA-seq. ITGA2B was selected as a candidate marker. Two different Polymerase Chain Reactions (PCR) were used to measure ITGA2B in platelet samples from healthy controls (n = 150), patients with NSCLC (n = 243), and patients with benign pulmonary nodules (n = 141) in two cohorts.

Results: Platelet ITGA2B levels were significantly higher (p < 0.001) in patients with NSCLC than in all controls. The diagnostic accuracy of ITGA2B was area under the curve (AUC) of 0.922 [95% confidence interval (CI), 0.892-0.952], sensitivity of 92.8%, and specificity of 78.6% in the test cohort and 0.888, 91.2%, and 56.5% in the validation cohort for NSCLC by quantitative real time PCR (q-PCR). Furthermore, ITGA2B maintained diagnostic accuracy for patients with NSCLC using Droplet Digital PCR (ddPCR) and the other type of internal control, Ribosomal Protein L32 (RPL32) [ddPCR: 0.967 (0.929-1.000) and RPL32: 0.847(0.773-0.920)]. A nomogram incorporating ITGA2B, carcinoembryonic antigen (CEA) and stage could predict the overall survival (C-index = 0.756).

Conclusions: TEP ITGA2B is a promising marker to improve identification of patients with stage I NSCLC and differentiate malignant from benign lung nodules.

Keywords: NSCLC, diagnosis, survival, tumor-educated blood platelets, ITGA2B


Citation styles

APA
Xing, S., Zeng, T., Xue, N., He, Y., Lai, Y.z., Li, H.l., Huang, Q., Chen, S.l., Liu, W.l. (2019). Development and Validation of Tumor-educated Blood Platelets Integrin Alpha 2b (ITGA2B) RNA for Diagnosis and Prognosis of Non-small-cell Lung Cancer through RNA-seq. International Journal of Biological Sciences, 15(9), 1977-1992. https://doi.org/10.7150/ijbs.36284.

ACS
Xing, S.; Zeng, T.; Xue, N.; He, Y.; Lai, Y.z.; Li, H.l.; Huang, Q.; Chen, S.l.; Liu, W.l. Development and Validation of Tumor-educated Blood Platelets Integrin Alpha 2b (ITGA2B) RNA for Diagnosis and Prognosis of Non-small-cell Lung Cancer through RNA-seq. Int. J. Biol. Sci. 2019, 15 (9), 1977-1992. DOI: 10.7150/ijbs.36284.

NLM
Xing S, Zeng T, Xue N, He Y, Lai Yz, Li Hl, Huang Q, Chen Sl, Liu Wl. Development and Validation of Tumor-educated Blood Platelets Integrin Alpha 2b (ITGA2B) RNA for Diagnosis and Prognosis of Non-small-cell Lung Cancer through RNA-seq. Int J Biol Sci 2019; 15(9):1977-1992. doi:10.7150/ijbs.36284. https://www.ijbs.com/v15p1977.htm

CSE
Xing S, Zeng T, Xue N, He Y, Lai Yz, Li Hl, Huang Q, Chen Sl, Liu Wl. 2019. Development and Validation of Tumor-educated Blood Platelets Integrin Alpha 2b (ITGA2B) RNA for Diagnosis and Prognosis of Non-small-cell Lung Cancer through RNA-seq. Int J Biol Sci. 15(9):1977-1992.

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