Effect Of CRP And CRP/ALB Ratio On Prognosis Of Advanced NSCLC And Related Mechanisms

Objective:To study the prognostic effect of systemic inflammatory markers C-reactive protein(CRP)and CRP/ALB on advanced non-small cell lung cancer(NSCLC)and its related mechanism.Methods:We retrospectively analyzed 436 inoperable late stage NSCLC patients.The total survival was calculated by Kaplan-Meier method,and survival differences were evaluated by single-factor log-rank and multifactor COX regression models.The ROC curve was drawn to compare the accuracy of predicting survival of advanced NSCLC by calculating the area under the curve(AUC).The correlation between CRP/ALB ratio and growth rate of lung adenocarcinoma and lung squamous cell carcinoma cell line was verified by animal experiments.The effects of CRP on proliferation,invasion,apoptosis and signal transduction pathways(NF-κB,AKT,STAT3)of lung cancer cells stimulated by IL-6 were studied by co-culture of primary L02 hepatocytes with lung cancer cells.Results:A total of 436 patients were included in this study.The results showed that patients with high CRP/ALB ratio had worse prognosis and shorter survival time(P<0.001);multivariate COX regression analysis showed that CRP/ALB ratio was an independent prognostic factor for survival(HR=1.825,P<0.001);and the prognostic predictive ability was superior to other systemic inflammatory indicators.According to the stratified analysis of different pathological types,the patients with higher CRP/ALB ratio had worse prognosis and shorter survival time(P<0.005)in non-squamous cell carcinoma group and squamous cell carcinoma group.In non-squamous cell carcinoma group,CRP/ALB ratio was also an independent prognostic factor for survival(HR=1.907,P<0.001),but the difference was that in squamous cell carcinoma group,CRP/ALB ratio was not an independent prognostic factor for survival.In animal experiments,there was a positive correlation between the tumorigenic capacity of lung adenocarcinoma cell lines and CRP/ALB ratio,which did not exist in lung squamous cell carcinoma cell lines.In vitro,IL-6 significantly promoted the secretion of CRP protein in hepatocyte/lung adenocarcinoma(A549,H1975)co-culture system and the proliferation and invasion of A549,H1975 cells,activated the phosphorylation of NF-κB p65 and STAT3;increased the content of ALB protein and decreased the CRP/ALB ratio,the ability of the proliferation and invasiveness of A549 and H1975 cells,and activation of NF-κB p65 phosphorylation and STAT3 phosphorylation stimulated by IL-6 disappeared.Conclusion:Advanced NSCLC patients with high CRP/ALB ratio have poor prognosis,and CRP/ALB ratio can better predict prognosis than other systemic inflammatory markers.Animal and cell experiments showed that ALB regulated the proliferation and invasion of CRP-induced lung adenocarcinoma cells via NF-κB and STAT3 pathways.