Furthermore, the elevated expressions of SIX2, SIX4, and SIX6 predicted poor overall survival (OS) in NSCLC (SIX2: HR = 1.14, 95 % CI, 1.00–1.31; SIX4: HR = 1.39, 95 % CI, 1.16–1.66; SIX6: HR = 1.18, 95 % CI, 1.00–1.38) and poor relapse-free survival (RFS) in lung adenocarcinoma (ADC) (SIX2: HR = 1.42, 95 % CI, 1.14–1.77; SIX4: HR = 1.52, 95 % CI, 1.09–2.11; SIX6: HR = 1.25, 95 % CI, 1.01–1.56). Here, SIX4 is linked to lung adenocarcinoma.