The Prognostic Value of Sex-Determining Region Y-Box 2 and CD8+ Tumor-Infiltrating Lymphocytes in Limited-Stage Small-Cell Lung Cancer

Abstract

<b><i>Background:</i></b> Sex-determining region Y-box 2 (SOX2) is a transcriptional factor that drives embryonic stem cells to neuroendocrine cells in lung development and is highly expressed in small-cell lung cancer (SCLC). However, the prognostic role of SOX2 and its relationship with tumor-infiltrating lymphocytes (TILs) has not been determined in SCLC. Herein, we assessed the expression of SOX2 and CD8+ TILs to obtain insights into the prognostic role of SOX2 and CD8+ TILs in limited-stage (LS)-SCLC. <b><i>Methods:</i></b> A total of 75 patients with LS-SCLC was enrolled. The SOX2 expression and CD8+ TILs were evaluated by immunohistochemistry. <b><i>Results:</i></b> High SOX2 and CD8+ TIL levels were identified in 52 (69.3%) and 40 (53.3%) patients, respectively. High SOX2 expression was correlated with increased density of CD8+ TILs (<i>p</i> = 0.041). Unlike SOX2, high CD8+ TIL numbers were associated with significantly longer progression-free survival (PFS; 13.9 vs. 8.0 months, <i>p</i> = 0.014). Patients with both high SOX2 expression and CD8+ TIL numbers (<i>n</i> = 29, 38.7%) had significantly longer PFS and overall survival (OS) compared to those from the other groups (median PFS 19.3 vs. 8.4 months; <i>p</i> = 0.002 and median OS 35.7 vs. 17.4 months; <i>p</i> = 0.004, respectively). Multivariate Cox regression analysis showed that the combination of high SOX2 expression and CD8+ TIL levels was an independent good prognostic factor for OS (HR = 0.471, 95% CI, 0.250–0.887, <i>p</i> = 0.02) and PFS (HR = 0.447, 95% CI, 0.250–0.801, <i>p</i> = 0.007) in SCLC. <b><i>Conclusions:</i></b> Evaluation of the combination of SOX2 and CD8+ TIL levels may be of a prognostic value in LS-SCLC.