ArticleJournal of the National Cancer Institute2022
Discoidin Domain Receptor-Driven Gene Signatures as Markers of Patient Response to Anti-PD-L1 Immune Checkpoint Therapy.
Article in Journal of the National Cancer Institute, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- A molecular landscape tracking the progression of non-muscle invasive bladder cancer.World journal of urology · 2026Review
- The extracellular matrix in inflammation and cancer.Molecular biomedicine · 2026Review
- Article
- Targeted DDR1 Treatment Strategy Enhances PD-1 Immunotherapy Efficacy against Gastric Cancer.Journal of medicinal chemistry · 2025Article
- Collagen in pituitary adenomas: A comprehensive review of biological roles and clinical implications.Journal of clinical & translational endocrinology · 2025Review
- DDR1 Targeting HOXA6 Facilitates Bladder Cancer Progression via Inhibiting Ferroptosis.Journal of cellular and molecular medicine · 2025Article
- Molecular biomarkers of progression in non-muscle-invasive bladder cancer - beyond conventional risk stratification.Nature reviews. Urology · 2025Review
- Integrative Analysis Reveals Differential Characteristics of DDR1 Mutant and Wild-type Gastric Cancers and Constructs their Prediction Models.Current medicinal chemistry · 2025Article
- Bladder cancer.Nature reviews. Disease primers · 2023Review
- Identifying novel biomarkers associated with bladder cancer treatment outcomes.Frontiers in oncology · 2023Review
- The oligometastatic spectrum in the era of improved detection and modern systemic therapy.Nature reviews. Clinical oncology · 2022Review
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundAnti-programmed cell death 1 (anti-PD-1) and PD ligand 1 (PD-L1) immune checkpoint therapies (ICTs) provided durable responses only in a subset of cancer patients. Thus, biomarkers are needed to predict nonresponders and offer them alternative treatments. We recently implicated discoidin domain receptor tyrosine kinase 2 (DDR2) as a contributor to anti-PD-1 resistance in animal models; therefore, we sought to investigate whether this gene family may provide ICT response prediction.
methodsWe assessed mRNA expression of DDR2 and its family member DDR1. Transcriptome analysis of bladder cancer (BCa) models in which DDR1 and 2 were perturbed was used to derive DDR1- and DDR2-driven signature scores. DDR mRNA expression and gene signature scores were evaluated using BCa-The Cancer Genome Atlas (n = 259) and IMvigor210 (n = 298) datasets, and their relationship to BCa subtypes, pathway enrichment, and immune deconvolution analyses was performed. The potential of DDR-driven signatures to predict ICT response was evaluated and independently validated through a statistical framework in bladder and lung cancer cohorts. All statistical tests were 2-sided.
resultsDDR1 and DDR2 showed mutually exclusive gene expression patterns in human tumors. DDR2high BCa exhibited activation of immune pathways and a high immune score, indicative of a T-cell-inflamed phenotype, whereas DDR1high BCa exhibited a non-T-cell-inflamed phenotype. In IMvigor210 cohort, tumors with high DDR1 (hazard ratio [HR] = 1.53, 95% confidence interval [CI] = 1.16 to 2.06; P = .003) or DDR2 (HR = 1.42, 95% CI = 1.01 to 1.92; P = .04) scores had poor overall survival. Of note, DDR2high tumors from IMvigor210 and CheckMate 275 (n = 73) cohorts exhibited poorer overall survival (HR = 1.56, 95% CI = 1.20 to 2.06; P < .001) and progression-free survival (HR = 1.77 95%, CI = 1.05 to 3.00; P = .047), respectively. This result was validated in independent cancer datasets.
conclusionsThese findings implicate DDR1 and DDR2 driven signature scores in predicting ICT response.
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