Fig. 2: Novel NSCLC subtype associated with poor survival.

a Overlap of subtype features between the five NMF subtypes in this study and subtypes identified in previous NSCLC multiomics studies. Protein enrichment is in the heatmap. Full rectangle and asterisk indicate significant overlaps (Two-sided fisher’s exact test adjusted P ≤ 0.05, Benjamini-Hochberg adjustment), faint rectangle indicates overlaps which pass only nominal P value (Two-sided fisher’s exact test P ≤ 0.05, two-sided fisher’s exact test adjusted P > 0.05), and blank indicates overlaps which is not significant (two-sided fisher’s exact test P > 0.05). b, c Reclassification of samples from previously defined multiomics subtypes^10,13 according to our combined NMF subtypes. The statistical significance of the relationship is visually represented by the clarity and transparency of the lines (Supplementary Fig. 2c). d Subtype 4-specific kinase activity scores estimated from phosphoproteomic data and the kinase-substrate network database (PHONEMeS). The colors of the points represent the estimated kinase activity scores. The sizes of the points represent the -log₁₀(FDR) of the kinase activity estimates. There were two significantly upregulated kinases: CSNK2A1 and GSK3B (FDR < 0.05). e Expression of poor prognosis markers containing phosphorylated sites on SLK (S347) and LRRFIP1 (S581) is shown for our study (Subtype 4, n = 43; others, n = 186) and CPTAC (LUAD (Subtype 4, n = 26; others, n = 84), LSCC (Subtype 4, n = 15; others, n = 93)). Wilcoxon rank-sum test was performed to test the differences in expression. The color of the dots in the right panel represents the study type in CPTAC. For box-plots, middle line, median: box edges, 25th and 75th percentiles; whiskers, most extreme points that do not exceed ±1.5 × IQR. f Cancer-specific overall survival length according to the expression of poor prognosis markers in our study and the CPTAC dataset (integrated with LUAD and LSCC). The p-value was calculated with the log-rank test. g Intracellular signaling pathways underlying poor prognosis in Subtype 4. The blue box represents the main signaling pathways, including the HIF-1, VEGF, PI3K-AKT, and NF-κB signaling pathways. The red triangular nodes are kinases identified as significantly upregulated in Subtype 4. The colors of the points represent the log₂FC values obtained through differential expression (DE) analysis of Subtype 4 and the other subtypes. The border style of the point indicates the prognostic direction of the feature. h Cancer-specific overall survival length between our subtypes indicating significant changes in survival probability (y-axis) over time (x-axis). i Survival curves for patients with (n = 35) and without metastasis (n = 8) in Subtype 4 (n = 43) and ( j) patients without metastasis in each subtype (n = 91). The p-value was calculated with the log-rank test (h–j).