A systematic dissection of the epigenomic heterogeneity of lung adenocarcinoma reveals two different subclasses with distinct prognosis and core regulatory networks.

摘要: Background Lung adenocarcinoma (LUAD) is a highly malignant and heterogeneous tumor that involves various oncogenic genetic alterations. Epigenetic processes play important roles in lung cancer development. However, the variation enhancer super-enhancer landscapes of LUAD patients remains largely unknown. To provide an in-depth understanding epigenomic heterogeneity LUAD, we investigate H3K27ac histone modification profiles tumors adjacent normal tissues from 42 explore role epigenetic alterations progression. Results A high intertumoral observed across profiles. We quantitatively model variability levels at proximal gene promoters distal enhancers propose new classification patients. Our defines two subgroups which are related to histological subtypes. Group II have significantly worse prognosis than group I, further confirmed public TCGA-LUAD cohort. Differential RNA-seq analysis between I groups reveals those genes upregulated tend promote cell proliferation induce de-differentiation. construct co-expression networks identify group-specific core regulators. Most these regulators linked with regulatory elements, such as super-enhancers. show CLU regulated by 3 I-specific works novel suppressor LUAD. Conclusions study systematically characterizes during progression provides helpful for predicting patient prognosis.