非小细胞肺癌患者尿蛋白质组差异表达分析

BACKGROUND AND OBJECTIVE: Screen differentially expressed proteins in patients with non-small cell lung cancer (NSCLC), and aim to identify biomarkers for early screening, monitoring prognosis and evaluating therapy of NSCLC. METHODS: Urinary samples were collected from 40 newly diagnosed NSCLC patients, 8 patients with lung benign disorders and 22 healthy people. 0.9% sodium dodecylsulfate- polyacrylamide gel electrophoresis (1D SDS-PAGE) and MS-Thermo-Orbitrap-Velos were applied to separate, extract and identify proteins in urinary samples from non-neoplastic groups and NSCLC patients, in order to find out differentially expressed proteins in patients with NSCLC. Then, sensitivity and specificity of candidate proteins were tested by certain experiments. Finally, biomarkers related to NSCLC could be determined. RESULTS: The differences of urinary proteins between non-neoplastic groups and NSCLC patients mainly focused on 90 kDa, 60 kDa and 20 kDa-30 kDa stripes. Four differently expressed proteins were found in urinary proteins in NSCLC group, including LRG1, CA1 (up-regulating proteins) and VPS4B, YWHAZ (down-regulating proteins). The sensitivity of these four proteins for biomarker of NSCLC was relatively low when they were used to screen or diagnose independently. The sensitivity and specificity of LRG1 was 83.0% (25/30) and 90.0% (18/20), respectively; 60.0% (18/30) and 90.0% (18/20) for CA1; 73.3% (22/30) and 90.0% (18/20) for VPS4B; 60.0% (18/30) and 95.0% (19/20) for YWHAZ. However, the sensitivity and specificity would increase to 96.7% (29/30) and 85% (17/20) after the four biomarkers were combined. CONCLUSION: LRG1 and CA1 are abundant in urine in patients with NSCLC, while VPS4B and YWHAZ are low-abundance proteins. They could be regarded as biomarkers for early screening, monitoring prognosis and evaluating therapy of patients with NSCLC because of differential expression. The sensitivity of the four biomarkers of NSCLC is relatively low when they are used to screen or diagnose independently, while significantly improvement if they were in combined pattern, which will be of excellent applications to clinical diagnosis and treatment.