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Objective: To investigate the correlation and overlaps between PD-L1 expression and classical genomic aberrations in Chinese lung adenocarcinoma (LADC) patients. Methods: We reviewed 428 consecutive, surgically resected cases of LADC from October 2015 to December 2016 from our center. PD-L1 expression was evaluated based on tumor proportion score (TPS). Correlation and co-occurrence of PD-L1 expression level with those of classical driver genes, such as EGFR, ALK, ROS-1, and KRAS and with clinical variables and disease-free survival (DFS) were analyzed. Results: Seventy of the 428 cases (16.4%) showed TPS ≥ 1%, and 21 cases (4.9%) showed TPS ≥ 50%. PD-L1 positive expression was significantly associated with male gender, smoking, advanced TNM stage, and solid histologic subtype. Both TPS ≥ 1% and ≥ 50% were correlated with the absence of an EGFR mutation (P < 0.001) and the presence of ALK rearrangement (P = 0.024). KRAS mutation was associated with TPS ≥ 50% (P = 0.035). PD-L1 positivity commonly overlapped with the alterations of classical driver oncogenes (58.5% with TPS ≥ 1% and 42.9% with TPS ≥ 50%). Approximately three-quarters of PD-L1 positive cases co-occurred with classical therapeutic-gene aberrations in cases with stage III/IV cancer or cancer progression. LADC could be divided into four subgroups based on the expression profile of current routine biomarkers for potential therapeutic strategies. Conclusions: PD-L1 expression is not only closely correlated with classic gene alterations but also commonly overlaps with the aberrations of classical driver oncogenes in Chinese LADC patients. These findings provide a useful overview of clinical strategies that rely on the profile of routinely used molecular biomarkers. [ABSTRACT FROM AUTHOR]