ATF4 and SLC7A11 as biomarkers predicting progression and prognosis in lung adenocarcinoma

Abstract

Lung adenocarcinoma (LUAD) is the most prevalent subtype of non-small cell lung cancer, yet reliable biomarkers for stratifying early-stage patients at high risk of progression and poor prognosis remain limited. We enrolled 168 LUAD patients who underwent surgery at The Fourth Hospital of Hebei Medical University. ATF4 and SLC7A11 expressions were assessed by immunohistochemistry. Associations with clinicopathological features were evaluated by χ²/Fisher’s exact tests; univariate and multivariate Cox regression analyses of overall survival (OS) and metastasis-free survival (MFS) were performed, and model discrimination was quantified by the concordance index (C-index). ATF4 was nuclear-positive in 55.4% of tumors, and SLC7A11 was cytoplasmic-positive in 59.5% of tumors. Neither ATF4 nor SLC7A11 was positively expressed in the stromal cells. The expression of ATF4 and SLC7A11 in tissues with pathological necrosis was enhanced. Both ATF4 and SLC7A11 correlated with aggressive features (more aggressive pathological subtypes with malignant potential, advanced clinical stage, lymph node metastasis, poor differentiation, pleural invasion, and pathological necrosis). ATF4 expression was also associated with lymphatic/vascular invasion. ATF4 (HR = 1.533, 95% CI, 1.040-2.259; P  = 0.031) and SLC7A11 (HR = 1.527, 95% CI, 1.013-2.303; P  = 0.043) were both independent prognostic factors for OS. As a combined indicator, ATF4 and SLC7A11 can enhance the C-index of the prognostic prediction model, and either positive for ATF4 or SLC7A11 have the highest C-index, regardless of whether it is for OS or MFS. ATF4/SLC7A11 are clinically useful prognostic biomarkers in LUAD. Either ATF4- or SLC7A11-positive expression appears to yield enhanced predictive value and may help identify high-risk patients for intensified surveillance.