biostudies-literatureDolgalev INCI NIH HHS6764https://www.ebi.ac.uk/biostudies/studies/S-EPMC10632519biostudies-literatureUnknown14(1)Approximately 30% of early-stage lung adenocarcinoma patients present with disease progression after successful surgical resection. Despite efforts of mapping the genetic landscape, there has been limited success in discovering predictive biomarkers of disease outcomes. Here we performed a systematic multi-omic assessment of 143 tumors and matched tumor-adjacent, histologically-normal lung tissue with long-term patient follow-up. Through histologic, mutational, and transcriptomic profiling of tumor and adjacent-normal tissue, we identified an inflammatory gene signature in tumor-adjacent tissue as the strongest clinical predictor of disease progression. Single-cell transcriptomic analysis demonstrated the progression-associated inflammatory signature was expressed in both immune and non-imNature communicationsInflammation in the tumor-adjacent lung as a predictor of clinical outcome in lung adenocarcinoma.PMC10632519P30 CA016087U2C CA271890U01 CA214195R37 CA244775Coudray NSterman DHPapagiannakopoulos TStransky NDavis FPMurrell NCai JSmolen GAWong KKGoparaju CMeyn PSnuderl MPass HIHeguy AMoreira ALPunekar SSydney IRamaswami SDolgalev IZhou HSulaiman IVelcheti VSegal LNKulicke RCheng WYLe HYeaton AMohamed HPoirier JTShiomi TTsirigos ANadorp BLi YChiriboga LSakellaropoulos TZhu KVasudevaraja VNeel BNarula NTsay JJfalseInflammation in the tumor-adjacent lung as a predictor of clinical outcome in lung adenocarcinoma.Approximately 30% of early-stage lung adenocarcinoma patients present with disease progression after successful surgical resection. Despite efforts of mapping the genetic landscape, there has been limited success in discovering predictive biomarkers of disease outcomes. Here we performed a systematic multi-omic assessment of 143 tumors and matched tumor-adjacent, histologically-normal lung tissue with long-term patient follow-up. Through histologic, mutational, and transcriptomic profiling of tumor and adjacent-normal tissue, we identified an inflammatory gene signature in tumor-adjacent tissue as the strongest clinical predictor of disease progression. Single-cell transcriptomic analysis demonstrated the progression-associated inflammatory signature was expressed in both immune and non-im2023-01-01T00:00:00Z2023 Nov2026-05-29T01:52:56.002Z2025-04-19T12:52:07.631ZS-EPMC106325193793858010.1038/s41467-023-42327-x