Prognostic significance of PIK3CA and SOX2 in Asian patients with lung squamous cell carcinoma

Iijima,Yoshihito; Seike,Masahiro; Noro,Rintaro; Ibi,Takayuki; Takeuchi,Shingo; Mikami,Iwao; Koizumi,Kiyoshi; Usuda,Jitsuo; Gemma,Akihiko

doi:10.3892/ijo.2014.2742

Prognostic significance of PIK3CA and SOX2 in Asian patients with lung squamous cell carcinoma

Authors:
- Yoshihito Iijima
- Masahiro Seike
- Rintaro Noro
- Takayuki Ibi
- Shingo Takeuchi
- Iwao Mikami
- Kiyoshi Koizumi
- Jitsuo Usuda
- Akihiko Gemma
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Affiliations: Department of Thoracic Surgery, Graduate School of Medicine, Nippon Medical School, Tokyo 113‑8603, Japan, Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo 113‑8603, Japan, Department of Thoracic Surgery, Aizu Chuo Hospital, Fukushima 965-8611, Japan
Published online on: November 10, 2014 https://doi.org/10.3892/ijo.2014.2742
Pages: 505-512
Copyright: © Iijima et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The recent development of human genome studies has demonstrated the possibility of alteration of several genes as oncogenic driver mutations of lung squamous cell carcinoma (SQCC). FGFR1, PIK3CA and SOX2 genes have been recognized as candidate driver genes of SQCC. The aim of the present study was to evaluate FGFR1, PIK3CA and SOX2 protein expression in SQCC and determine whether the expression of these can be used as prognostic biomarkers. We evaluated the relationships between FGFR1, PIK3CA and SOX2 expression by immunohistochemical analysis and overall survival in lung SQCC patients with stage I-III that originated from China, United States and Japan. FGFR1-positive, PIK3CA-negative and SOX2-positive staining each showed trends toward better survival, although the differences were not statistically significant in a Chinese cohort of 57 patients. Patients with PIK3CA-negative and SOX2-positive staining (PIK3CA-/SOX2+) showed better prognosis compared with those with PIK3CA-positive or SOX2-negative staining in the Chinese cohort (p=0.04). The robustness of PIK3CA-/SOX2+ classification as having prognostic significance was validated in an independent set of 66 Japanese cohort patients (p=0.007). Japanese SQCC patients with stage I were evaluated separately and PIK3CA-/SOX2+ cases had significantly better survival than the group with PIK3CA-positive or SOX2-negative status (p=0.03). In univariate and multivariable Cox proportional hazards models of Asian stage I patients, the PIK3CA-/SOX2+ classification was statistically significantly associated with survival and was an independent prognostic factor. Classification by PIK3CA and SOX2 protein expression is useful for predicting the prognosis of Asian patients with lung SQCC with stage I.

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