{"doi":"10.1038/s43018-024-00883-1","title":"Prospective validation of ORACLE, a clonal expression biomarker associated with survival of patients with lung adenocarcinoma","abstract":"Human tumors are diverse in their natural history and response to treatment, which in part results from genetic and transcriptomic heterogeneity. In clinical practice, single-site needle biopsies are used to sample this diversity, but cancer biomarkers may be confounded by spatiogenomic heterogeneity within individual tumors. Here we investigate clonally expressed genes as a solution to the sampling bias problem by analyzing multiregion whole-exome and RNA sequencing data for 450 tumor regions from 184 patients with lung adenocarcinoma in the TRACERx study. We prospectively validate the survival association of a clonal expression biomarker, Outcome Risk Associated Clonal Lung Expression (ORACLE), in combination with clinicopathological risk factors, and in stage I disease. We expand our mechanistic understanding, discovering that clonal transcriptional signals are detectable before tissue invasion, act as a molecular fingerprint for lethal metastatic clones and predict chemotherapy sensitivity. Lastly, we find that ORACLE summarizes the prognostic information encoded by genetic evolutionary measures, including chromosomal instability, as a concise 23-transcript assay.","journal":"Nature Cancer","year":2025,"id":511950,"datarank":0.45571995884607397,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.059861359403785036,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.059861359403785036,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":12,"citers_with_citation_signal":4,"citers_with_endowment":4,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9601,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT01888601"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1370782,"name":"Yun-Hsin Liu","orcid":"0009-0001-1508-5276","position":1,"is_corresponding":false},{"id":832,"name":"Javier Herrero","orcid":"0000-0001-7313-717X","position":2,"is_corresponding":false},{"id":848343,"name":"Yin Wu","orcid":"0000-0003-4080-3935","position":3,"is_corresponding":false},{"id":230052,"name":"David A. 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