*3.4. RUNX1 A*ff*ects Overall Survival in Adenocarcinoma*

To elucidate the effect of RUNX1 expression on survival of NSCLC patient, we analyzed the expression of RUNX1 using immunohistochemistry of formalin-fixed paraffin-embedded tumor tissues from 409 NSCLCs. Representative positive staining patterns of RUNX1 are shown in adenocarcinoma and squamous cell carcinoma (Figure 4A). Clinicopathological characteristics of 409 non-small cell lung cancer patients are listed in Table S2. The median follow-up period of patients was 5.2 years. RUNX1 expression was reduced in 31% of the samples. Reduced RUNX1 expression was not related to pathologic stage (Figure S2), but was found more frequently in woman (Figure 4B) and in adenocarcinoma (Figure 4C) and was significantly associated with poor overall survival in adenocarcinoma (*p* = 0.005; Figure 4D) but not in squamous cell carcinoma (*p* = 0.87). The median survival of adenocarcinoma patients with and without reduced RUNX1 expression was 41 and 81 months, respectively. Cox proportional hazards analysis also showed that overall survival of adenocarcinoma patients with reduced RUNX1 expression was approximately 1.97 (95% CI = 1.16–3.44; *p* = 0.01) times poorer than in those without, after controlling for age, recurrence, and pathologic stage (Table 1). However, RUNX1 expression was not associated with recurrence-free survival irrespective of histology in NSCLC (*p* = 0.21).


**Table 1.** Cox proportional hazards analysis of overall survival according to RUNX1 expression.

Abbreviations: Adeno, adenocarcinoma; squamous, squamous cell carcinoma; HR, hazard ratio; CI, confidence interval; RUNX1, runt-related transcription factor 1.

**Figure 4.** The effect of RUNX1 expression on overall survival in NSCLC. (**A**) RUNX1 expression was analyzed using immunohistochemistry in 409 NSCLC patients. Positive staining occurred in the nucleus of adenocarcinoma (upper) and squamous cell carcinoma. (X200). (**B**,**C**) Reduced expression levels were compared according to gender (**B**) and histologic subtypes (**C**). *p*-values are based on Student *t*-test. (**D**) The effect of reduced RUNX1 expression on overall survival of patients with adenocarcinoma was analyzed using Kaplan-Meier survival curve. *p*-value was calculated using log-rank test.
