In conclusion, through a three-step analysis, (i) exploration of candidate genes in a case–control setting, (ii) narrowing down candidate genes using a real-world cohort, and (iii) validation using TCGA data and combined cohorts, we identified that the lower expression of OLFM1 and BMP6 is a biomarker to identify patients with high-risk pStage I nonsquamous NSCLC with pure solid appearance at preoperative CT. Here, OLFM1 is linked to non-small cell lung carcinoma.