Decreased complement 4d increases poor prognosis in patients with non-small cell lung cancer combined with gastrointestinal lymph node metastasis

Lung cancer is a common malignancy that is difficult to treat and has a high risk of mortality. Although gastrointestinal lymph node metastasis has long been known to exert major impact on the prognosis of lung cancer, the mechanism of its occurrence and potential biological markers remain elusive. Therefore, the present study retrospectively analyzed data from 132 patients with non-small cell lung cancer (NSCLC) combined with lymph node metastasis between February 2010 and April 2019 from the First Affiliated Hospital of Soochow University (Suzhou, China) and Sichuan Cancer Hospital (Chengdu, China). Overall survival was assessed using Kaplan-Meier analysis and Cox logistic regression model. In addition, a prediction model was constructed based on immune indicators such as complement C3b and C4d (measured by ELISA), before the accuracy of this model was validated using calibration curves for 5-year OS. Among the 132 included patients, a total of 92 (70.0%) succumbed to the disease within 5 years. Multifactorial analysis revealed that complement C3b deficiency increased the risk of mortality by nearly two-fold [hazard ratio (HR)=2.23; 95% CI=1.20-4.14; P=0.017], whilst complement C4d deficiency similarly increased the risk of mortality by two-fold (HR=2.14; 95% CI=1.14-4.00; P=0.012). The variables were subsequently screened using Cox model to construct a prediction model based on complement C3b and C4d levels before a Nomogram plotted. By internal validation for the 132 patients, the Nomogram accurately estimated the risk of mortality, with a corrected C-index of 0.810. External validation of the model in another 50 patients from Sichuan Cancer Hospital revealed an accuracy of 77.0%. Overall, this mortality risk prediction model constructed based on complement levels showed accuracy in assessing the prognosis of patients with metastatic NSCLC. Therefore, complement C3b and C4d have potential for use as biomarkers to predict the risk of mortality in such patients.