{"doi":"10.1186/s12943-024-02160-2","title":"A prospective multi-cohort study identifies and validates a 5-gene peripheral blood signature predictive of immunotherapy response in non-small cell lung cancer","abstract":"BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape for non-small cell lung cancer (NSCLC). The variability in patient responses necessitates a blood-based, multi-cohort gene signature to predict ICI response in NSCLC. METHODS: We performed transcriptomic profiling of peripheral blood mononuclear cell (PBMC) and buffy coat (BC) samples from three independent cohorts of NSCLC patients treated with ICIs: a retrospective cohort (PMBCR, n = 59), a retrospective validation cohort (BC, n = 44), and a prospective validation cohort (PBMCP, n = 42). We identified a 5-gene signature (UQCRB, NDUFA3, CDKN2D, FMNL1-DT, and APOL3) predictive of ICI response and validated its clinical utility in the prospective PBMCP cohort. Response was evaluated using RECIST criteria, and patients were followed up for progression-free survival (PFS) and overall survival (OS). RESULTS: In the prospective PBMCP cohort, the 5-gene signature demonstrated high accuracy in stratifying patients into responders and non-responders (AUC = 0.89, 95% CI: 0.80-0.99). Predicted responders exhibited significantly longer PFS compared to predicted non-responders (median: 13.8 months vs. 4.2 months, HR = 0.21, 95% CI: 0.07-0.58, p = 0.005). CONCLUSION: Our study confirms a 5-gene signature as a key biomarker for ICI response in NSCLC, enhancing treatment precision.","journal":"Molecular Cancer","year":2024,"id":447809,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9053,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1265933,"name":"Fangfang Liu","orcid":"0000-0003-1059-8598","position":1,"is_corresponding":false},{"id":891401,"name":"Yuanyuan Fu","orcid":"0000-0001-7715-0558","position":2,"is_corresponding":false},{"id":440952,"name":"Chris K. Deng","orcid":null,"position":3,"is_corresponding":false},{"id":70015,"name":"Jeffrey A. Borgia","orcid":"0000-0002-1520-7966","position":4,"is_corresponding":false},{"id":1266453,"name":"A Ayman","orcid":null,"position":5,"is_corresponding":false},{"id":321924,"name":"Masaki Nasu","orcid":null,"position":6,"is_corresponding":false},{"id":320405,"name":"Mayumi Jijiwa","orcid":"0000-0003-1596-856X","position":7,"is_corresponding":false},{"id":350,"name":"Hua Yang","orcid":"0000-0002-4876-4072","position":8,"is_corresponding":false},{"id":432259,"name":"Ting Gong","orcid":"0000-0003-4844-0227","position":9,"is_corresponding":false},{"id":1265934,"name":"Junlong Wang","orcid":"0000-0002-3969-3321","position":10,"is_corresponding":false},{"id":1265935,"name":"Zhougui Ling","orcid":"0000-0003-1611-8946","position":11,"is_corresponding":false},{"id":699122,"name":"Xiaoyan Wang","orcid":"0000-0002-8763-289X","position":12,"is_corresponding":false},{"id":1265936,"name":"Hongwei Wang","orcid":"0000-0003-0697-5100","position":13,"is_corresponding":false},{"id":1265937,"name":"Qian Chu","orcid":"0000-0001-8192-7630","position":14,"is_corresponding":false},{"id":320407,"name":"Youping Deng","orcid":"0000-0002-5951-8213","position":15,"is_corresponding":false},{"id":697077,"name":"Shaoqiu Chen","orcid":"0000-0001-6532-1575","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-19T02:02:03.354708Z","pmid":"39506771","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}