Tumor Forkhead Box J2 as a Biomarker Reflecting Risks of Recurrence and Death in Non-Small Cell Lung Cancer Receiving Surgical Resection

Abstract

Forkhead box J2 (FOXJ2) induces cell apoptosis and restrains epithelial-mesenchymal transition in lung cancer, but its capability to serve as a prognostic biomarker in non-small cell lung cancer (NSCLC) remains unclear. Hence, this study intended to investigate the association of FOXJ2 with clinical characteristics, disease-free survival (DFS), and overall survival (OS) in NSCLC patients who received surgical resection. Totally, 182 NSCLC patients who received surgical resection were retrospectively enrolled. Their tumor FOXJ2 expression was quantified by immunohistochemistry (IHC). FOXJ2 IHC score = s taining intensity × density, with a total score of 12. FOXJ2 IHC score was 0 in 128 (70.3%) patients and > 0 in the remaining 54 (29.7%) patients; meanwhile, it was ≤ 3 in 157 (86.3%) patients and > 3 in 25 (13.7%) patients. FOXJ2 was negatively related to node (N) stage (P = 0.013) and tumor-nodes-metastasis (TNM) stage (P = 0.034). Intriguingly, FOXJ2 IHC score was reduced in patients with adjuvant chemotherapy than in patients without adjuvant chemotherapy (P = 0.036). The median DFS and OS (95% confidence interval) were 35.0 (31.3-38.7) months and 48.8 (43.7-53.9) months, respectively. Notably, FOXJ2 IHC score > 0 (P = 0.006) and > 3 (P = 0.002) was correlated with prolonged DFS. Also, FOXJ2 IHC score > 0 (P = 0.027) and > 3 (P = 0.028) was associated with longer OS. After adjustment by backward stepwise multivariate model, FOXJ2 IHC score > 3 was independently associated with prolonged DFS (hazard ratio = 0.367, P = 0.009). In conclusion, tumor FOXJ2 negatively links with N stage and TNM stage; moreover, FOXJ2 IHC score > 3 estimates prolonged DFS and OS in NSCLC patients who received surgical resection.