Complement and coagulation cascades pathway-related signature as a predictor of immunotherapy in metastatic urothelial cancer

• DOI: 10.18632/aging.205022
• Publication Date: 2023-09-24T14:22:47Z
• Authors: Zheng Gong; Yuming He; Xiao Mi; Chengcheng Li; Xiaoran Sun; Guoqiang Wang; Leo Li; Yusheng Han; Chunwei Xu; Wenxian Wang; Shangli Cai; Liang Wang; Zhongyuan Liu
• Keywords: 3. Good health; Research Paper

Background: Immune checkpoint inhibitors (ICIs) have shown efficacy in patients with metastatic urothelial cancer (mUC), however, only a small subset of could benefit from ICIs. Identifying predictive biomarkers ICIs mUC is clinical meaningful for patient stratification and administration. Methods: Clinical transcriptomic data treated cohort (IMvigor210 study) was utilized to explore the biomarkers. LASSO Cox regression performed construct model. The model trained tested cohort, then exploratively clear cell renal carcinoma (ccRCC) melanoma cohorts which also received regimens. Results: differentially expressed genes (DEGs) complement coagulation cascades pathway (CCCP) were mainly enriched non-responders cohort. A CCCP risk score constructed based on DEGs CCCP. Patients low-risk more responsive had better overall survival (OS) than those high-risk training set (HR, 0.38; 95%CI, 0.27-0.53, P<0.001) test 0.34; 0.17-0.71, P=0.003). association between OS remained significant multivariable cox by adjusting PD-L1 expression TMB (P<0.05). In addition, there no difference bladder without (TCGA-BLCA HR, 0.76, 0.49-1.18, P=0.22), suggesting but not prognostic effect score. For exploratory analysis, consistent results observed that group showed superior ccRCC 0.52, 0.37-0.75, 0.27, 0.12-0.62, P=0.001). Conclusions: Our study an independent biomarker predicts patients. tend response longer life time probably due immune-activated TME. Further studies are needed validate utility seven-gene signature.