Figure 1.

Three Subgroups of Never-Smoker Patients with LUAD with Clinicopathological Homogeneity

(A) Three distinct subgroups of cancer-immune gene expression in never-smoker lung adenocarcinoma. Whole-transcriptome sequencing data from 99 never-smoker patients with lung adenocarcinoma were analyzed by Gaussian Mixture Model using eight different gene panels (546 in total) in the cancer-immunity cycle (Figure S3 and Data S1), revealing three subgroups. Subgroup 1 was defective in antigen-presenting machinery, NK cell activation, and type I IFN production (later named as subgroup with ubiquitination functioning, deregulated type I IFN production, and defective antigen presentation type). Subgroup 2 was defective in ubiquitinating enzymes expression, and the type I IFN and TGF-β signaling pathways were significantly downregulated (later named as subgroup with defective ubiquitination, type I IFN signaling, antigen presentation type). Subgroups 1 and 2 showed mutually exclusive gene expression patterns within panels of the cancer-immunity cycle. Subgroup 3 maintained relatively high levels of MHC class II and other cancer-immune gene expression (later named as subgroup with ubiquitination, type I IFN pathway, antigen presentation functioning) (Table 1 and Data S2).

(B) Comparison of clinicopathological characteristics between subgroups.

(C) Spatial distribution of lymphocytes in tumor/stromal area. H&E slide image showed very few lymphocytes in the tumor nest (first row), and most distributed in the stromal areas (green, second row) across subgroups within the representative region of interest. The patterns of tumor-infiltrating lymphocytes in each subgroup were indistinguishable by routine pathological readings.