ArticleJournal of the National Cancer Institute2013
Investigation of complement activation product c4d as a diagnostic and prognostic biomarker for lung cancer.
Article in Journal of the National Cancer Institute, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed.
- Complement C3 overexpression activates JAK2/STAT3 pathway and correlates with gastric cancer progression.Journal of experimental & clinical cancer research : CR · 2020Trial
- Proteomic characterization of airway obstruction-associated proteins in non-smoking lung adenocarcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Circulating extracellular vesicles from early-stage lung cancer patients trigger endothelial activation to drive pre-metastatic niche formation through synergistic miR-29a and C4A signaling.Journal of experimental & clinical cancer research : CR · 2026Article
- Complement system in cancer: friend or foe of immunotherapy.Journal for immunotherapy of cancer · 2026Review
- Identification of High-Performing Blood Metabolite Biomarkers of Lung Cancer in a Chinese Population.Phenomics (Cham, Switzerland) · 2026Article
- The contribution of the membrane-bound complement regulatory proteins CD46 and CD55 in phases of acute lymphocytic leukemia and acute myelogenous leukemia.Scientific reports · 2026Article
- Complement system in tumor growth and metastases.British journal of cancer · 2026Review
- Biomarkers for the diagnosis of indeterminate pulmonary nodules: are we there yet?Journal of thoracic disease · 2025Review
- O-GalNAc Glycosylation Activates MBL-Mediated Complement and Coagulation Cascades to Drive Organotropic Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Genetically druggable targets for MAPK-activated colorectal cancer by a two-sample mendelian randomization analysis.Scientific reports · 2025Article
- Prognostic significance of serum complement activation, neutrophil extracellular traps and extracellular DNA in newly diagnosed epithelial ovarian cancer.Gynecologic oncology · 2025Article
- Identification of a coagulation-related classification and signature that predict disease heterogeneity for colorectal cancer and pan-cancer patients.Frontiers in immunology · 2025Article
- Complement and coagulation cascade cross-talk in endometriosis and the potential of Janus Kinase inhibitors-a network meta-analysis.Frontiers in immunology · 2025Article
- Impact of smoking on the complement system: a narrative review.Frontiers in immunology · 2025Review
- Role of Innate Immunity in Cancer.Advances in experimental medicine and biology · 2025Review
- Complement protein expression changes in various conditions of breast cancer: in-silico analyses-experimental research.Annals of medicine and surgery (2012) · 2024Article
- Comprehensive proteomic profiling of lung adenocarcinoma: development and validation of an innovative prognostic model.Translational cancer research · 2024Article
- Tea intake and lung diseases: a Mendelian randomization study.Frontiers in immunology · 2024Article
- Biomarkers of lung cancer for screening and in never-smokers-a narrative review.Translational lung cancer research · 2023Review
- Non-small cell lung carcinoma (NSCLC): Implications on molecular pathology and advances in early diagnostics and therapeutics.Genes & diseases · 2023Review
24 more citing papers are in PubMed but not listed here.
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14 authors.
Funding
Abstract
backgroundThere is a medical need for diagnostic biomarkers in lung cancer. We evaluated the diagnostic performance of complement activation fragments.
methodsWe assessed complement activation in four bronchial epithelial and seven lung cancer cell lines. C4d, a degradation product of complement activation, was determined in 90 primary lung tumors; bronchoalveolar lavage supernatants from patients with lung cancer (n = 50) and nonmalignant respiratory diseases (n = 22); and plasma samples from advanced (n = 50) and early lung cancer patients (n = 84) subjects with inflammatory lung diseases (n = 133), and asymptomatic individuals enrolled in a lung cancer computed tomography screening program (n = 190). Two-sided P values were calculated by Mann-Whitney U test.
resultsLung cancer cells activated the classical complement pathway mediated by C1q binding that was inhibited by phosphomonoesters. Survival was decreased in patients with high C4d deposition in tumors (hazard ratio [HR] = 3.06; 95% confidence interval [CI] = 1.18 to 7.91). C4d levels were increased in bronchoalveolar lavage fluid from lung cancer patients compared with patients with nonmalignant respiratory diseases (0.61 ± 0.87 vs 0.16 ± 0.11 µg/mL; P < .001). C4d levels in plasma samples from lung cancer patients at both advanced and early stages were also increased compared with control subjects (4.13 ± 2.02 vs 1.86 ± 0.95 µg/mL, P < 0.001; 3.18 ± 3.20 vs 1.13 ± 0.69 µg/mL, P < .001, respectively). C4d plasma levels were associated with shorter survival in patients at advanced (HR = 1.59; 95% CI = 0.97 to 2.60) and early stages (HR = 5.57; 95% CI = 1.60 to 19.39). Plasma C4d levels were reduced after surgical removal of lung tumors (P < .001) and were associated with increased lung cancer risk in asymptomatic individuals with (n = 32) or without lung cancer (n = 158) (odds ratio = 4.38; 95% CI = 1.61 to 11.93).
conclusionsComplement fragment C4d may serve as a biomarker for early diagnosis and prognosis of lung cancer.
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