Increasing serum complement component 1q is associated with worse prognosis in advanced non-small cell lung cancer treated with immune checkpoint inhibitors: a single-center, retrospective study.

ABSTRACT

Background: There is a lack of readily available clinical markers of non-small cell lung cancer (NSCLC) immunotherapy efficacy. Previous studies have found that overexpressed complement component 1q (C1q) promotes macrophage M2 polarization and an immunosuppressive tumor microenvironment. This study aimed to evaluate the association between serum C1q and the efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced NSCLC. Methods: A total of 168 patients with advanced NSCLC who received ICIs in the Renmin Hospital of Wuhan University were included in this study. Serum C1q levels were collected before and 3 weeks after immunotherapy treatment, together with other data on clinical and demographic characteristics. The primary outcome was overall survival (OS) (months from first dose of ICIs to death, censored at date of last follow-up). Secondary outcome was progression-free survival (PFS) [defined as months from first dose of ICIs to clinical or radiographic progression by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or death, censored at date of last follow-up] and objective response rate (ORR) which was defined as rate of complete response (CR) or partial response (PR) at best response by RECIST 1.1. Results: A total of 168 patients were included in this study, including 127 males (75.60%) and 41 females (24.40%). Thirty-nine patients achieved objective response (2 CR, 37 PR), and 111 patients (66.07%) had stable disease (SD) as best response. The ORR was 23.21% and the disease control rate was 89.28%. The upward trends of serum C1q levels between baseline and post-treatment were strongly associated with the shorter PFS [hazard ratio (HR) =1.554, 95% confidence interval (CI) 1.07-2.10, P=0.01] and OS (HR =1.444, 95% CI 1.01-1.98, P=0.03). Moreover, taking the median OS 18.9 months as the cut-off of prognosis, receiver operating characteristic (ROC) analysis showed that serum baseline C1q yielded an area under the ROC curve of 0.785 (95% CI 0.711-0.869). The optimal serum baseline C1q cut-off point to predict immunotherapy prognosis was 216.2 mg/L. Conclusions: These findings suggested that elevated serum C1q after ICIs treatment was related to a worse prognosis in NSCLC. Monitoring the baseline and dynamic data of C1q during hospitalization showed the potential to predict the prognosis of NSCLC patients.