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.

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.

• Authors: Shan Xing, Tao Zeng, Ning Xue, Yi He, Yan-Zhen Lai, Hui-Lan Li, Qi Huang, Shu-Lin Chen, Wan-Li Liu
• Journal: International journal of biological sciences (Int J Biol Sci) Vol. 15 Issue 9 Pg. 1977-1992 ( 2019) ISSN: 1449-2288 [Electronic] Australia
• PMID: 31523198 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• ITGA2B protein, human
• Integrin alpha2
• P-Selectin
• SELP protein, human

Topics

• Biomarkers, Tumor (metabolism)
• Blood Platelets (metabolism)
• Carcinoma, Non-Small-Cell Lung (metabolism, pathology)
• Female
• Humans
• Integrin alpha2 (genetics, metabolism)
• Lung Neoplasms (metabolism, pathology)
• Male
• Middle Aged
• P-Selectin (genetics, metabolism)
• Real-Time Polymerase Chain Reaction
• Sequence Analysis, RNA