ArticleAging2023
Complement and coagulation cascades pathway-related signature as a predictor of immunotherapy in metastatic urothelial cancer.
Article in Aging, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 17 citations in OpenAlex.
- Bioinformatics analysis of proteins in the complement and coagulation cascades in colon cancer: Discovering the potential biomarker SERPINA1.Oncology letters · 2026Article
- Survival prediction of colorectal cancer using 101 machine learning methods based on immune-related genes: A machine learning study.Medicine · 2026Article
- Complement and Coagulation Cascades Pathway was Inactivated in HIV-Associated Colorectal Cancer: Results from a Proteomics Study.Journal of Cancer · 2026Article
- Identification of DNA Replication Stress-Related Genes as Prognostic Biomarkers for Bladder Cancer.Combinatorial chemistry & high throughput screening · 2026Article
- Identification of cancer-associated fibroblast signature genes for potential biomarkers in cholangiocarcinoma: a Mendelian randomization study.Discover oncology · 2025Article
- Comprehensive analysis of coagulation-associated gene signature in bladder cancer diagnosis, prognosis, and immunotherapy.Scientific reports · 2025Article
- Identification of risk factors for high-risk dedifferentiation in papillary thyroid carcinoma and construction of discriminative model.Frontiers in oncology · 2025Article
- Identification of novel diagnostic biomarkers associated with liver metastasis in colon adenocarcinoma by machine learning.Discover oncology · 2024Article
- Antitumor Effects and the Potential Mechanism of 10-HDA against SU-DHL-2 Cells.Pharmaceuticals (Basel, Switzerland) · 2024Article
- PD1/PD-L1 blockade in clear cell renal cell carcinoma: mechanistic insights, clinical efficacy, and future perspectives.Molecular cancer · 2024Review
- Investigation of cellular communication and signaling pathways in tumor microenvironment for high TP53-expressing osteosarcoma cells through single-cell RNA sequencing.Medical oncology (Northwood, London, England) · 2024Article
- Proteomic profiling and biomarker discovery for predicting the response to PD-1 inhibitor immunotherapy in gastric cancer patients.Frontiers in pharmacology · 2024Article
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmune checkpoint inhibitors (ICIs) have shown efficacy in patients with metastatic urothelial cancer (mUC), however, only a small subset of patients could benefit from ICIs. Identifying predictive biomarkers of ICIs in patients with mUC is clinical meaningful for patient stratification and administration.
methodsClinical and transcriptomic data of mUC patients treated with ICIs from mUC cohort (IMvigor210 study) was utilized to explore the predictive biomarkers. LASSO Cox regression was performed to construct a predictive model. The predictive model was trained and tested in the mUC cohort, and then exploratively tested in clear cell renal cell carcinoma (ccRCC) and melanoma cohorts in which patients also received ICIs regimens.
resultsThe differentially expressed genes (DEGs) in complement and coagulation cascades pathway (CCCP) were mainly enriched in non-responders of ICIs in the mUC cohort. A CCCP risk score was constructed based on the DEGs in CCCP. Patients with a low-risk score were more responsive to ICIs and had better overall survival (OS) than those with a high-risk score in the training set (HR, 0.38; 95%CI, 0.27-0.53, P<0.001) and the test set (HR, 0.34; 95%CI, 0.17-0.71, P=0.003). The association between the CCCP risk score and OS remained significant in the multivariable cox regression by adjusting PD-L1 expression and TMB (P<0.05). In addition, there was no difference for OS in the bladder cancer patients without ICIs (TCGA-BLCA cohort, HR, 0.76, 95%CI, 0.49-1.18, P=0.22), suggesting a predictive but not prognostic effect of the risk score. For the exploratory analysis, consistent results were observed that low-risk group showed superior OS in ccRCC cohort (HR, 0.52, 95%CI, 0.37-0.75, P<0.001) and melanoma cohort (HR, 0.27, 95%CI, 0.12-0.62, P=0.001).
conclusionsOur study showed that the CCCP risk score is an independent biomarker that predicts the efficacy of ICIs in mUC patients. The patients with a low-risk score tend to have a better response to ICIs and a longer life time probably due to the immune-activated TME. Further studies are needed to validate the clinical utility of the seven-gene signature.
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