Overexpression of SOX2 Is Associated with Better Overall Survival in Squamous Cell Lung Cancer Patients Treated with Adjuvant Radiotherapy.
OBJECTIVE
The purpose of this study is to investigate the prognostic significance of SOX2 gene amplification and expression in patients with American Joint Committee on Cancer stage III lung squamous cell carcinoma (SCC) who underwent surgery followed by adjuvant radiotherapy.


METHODS
Pathological specimens were obtained from 33 patients with stage III lung SCC treated with surgery followed by adjuvant radiotherapy between 1996 and 2008. SOX2 gene amplification and protein expression were analyzed using fluorescent in situ hybridization and immunohistochemistry, respectively. Patients were divided into two groups according to their SOX2 gene amplification and protein expression status. Kaplan-Meier estimates and a Cox proportional hazards model were used to identify the prognostic factors affecting patient survival.


RESULTS
The median follow-up period for surviving patients was 58 months (range, 5 to 102 months). SOX2 gene amplification was observed in 22 patients and protein overexpression in 26 patients. SOX2 overexpression showed significant association with SOX2 gene amplification (p=0.002). In multivariate analysis, SOX2 overexpression was a significant prognostic factor for overall survival (OS) (hazard ratios [HR], 0.1; 95% confidence interval [CI], 0.002 to 0.5; p=0.005) and disease-free survival (DFS) (HR, 0.15; 95% CI, 0.04 to 0.65; p=0.01). Age (HR, 0.33; 95% CI, 0.11 to 0.98; p=0.046) and total radiation dose (HR, 0.13; 95% CI, 0.02 to 0.7; p=0.02) were the independent prognostic factors for OS and DFS. Patients with SOX2 amplification did not show a longer OS (p=0.95) and DFS (p=0.48).


CONCLUSIONS
Our data suggested that SOX2 overexpression could be used as a positive prognostic factor in patients with stage III lung SCC receiving adjuvant radiotherapy.
Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.|Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
Hong In
HI
Yoon
Yonsei Song-Dang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Korea.
Kyu Hyun
KH
Park
Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
Eun-Jung
EJ
Lee
Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
Ki Chang
KC
Keum
Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
Chang Geol
CG
Lee
Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Chul Hoon
CH
Kim
Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.|Yonsei Song-Dang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Korea.
Yong Bae
YB
Kim
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D018572:Disease-Free Survival; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D018714:Radiotherapy, Adjuvant; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis*
C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors
Carcinoma; Lung neoplasms; Overexpression; Radiotherapy; SOX-2; Squamous cell