Quantitative proteomics identified circulating biomarkers in lung adenocarcinoma diagnosis

Lung cancer (LC) is a common malignant tumor with a high incidence and poor prognosis. Early LC could be cured, but the 5-year-survival rate for patients advanced is extremely low. Early screening of tumor biomarkers through plasma could allow more LC to be detected at an early stage, leading to a earlier treatment and a better prognosis.

This study was based on total proteomic analysis and parallel reaction monitoring validation of peripheral blood from 20 lung adenocarcinoma patients and 20 healthy individuals. Furthermore, differentially expressed proteins closely related to prognosis were analysed using Kaplan-Meier Plotter and receiver operating characteristic curve (ROC) curve analysis.

The candidate proteins GAPDH and RAC1 showed the highest connectivity with other differentially expressed proteins between the lung adenocarcinoma group and the healthy group using STRING. Kaplan-Meier Plotter analysis showed that lung adenocarcinoma patients with positive ATCR2, FHL1, RAB27B, and RAP1B expression had observably longer overall survival than patients with negative expression (P < 0.05). The high expression of ARPC2, PFKP, PNP, RAC1 was observably negatively correlated with prognosis (P < 0.05). 17 out of 27 proteins showed a high area under the curve (> 0.80) between the lung adenocarcinoma and healthy plasma groups. Among those proteins, UQCRC1 had an area under the curve of 0.960, and 5 proteins had an area under the curve from 0.90 to 0.95, suggesting that these hub proteins might have discriminatory potential in lung adenocarcinoma, P < 0.05.

These findings provide UQCRC1, GAPDH, RAC1, PFKP have potential as novel biomarkers for the early screening of lung adenocarcinoma.