J Cancer 2017; 8(12):2410-2416. doi:10.7150/jca.20069

Research Paper

DNA-dependent protein kinase catalytic subunit functions in metastasis and influences survival in advanced-stage laryngeal squamous cell carcinoma

Sha-sha He 1,3#, Yong Chen 1,3#, Xiao-ming Shen 1,6#, Hong-zhi Wang7, Peng Sun1,5, Jun Dong 1,2, Gui-fang Guo 1,2, Ju-gao Chen1, Liang-ping Xia 1,2, Pei-li Hu 1,2, Hui-juan Qiu 1,2, Shou-sheng Liu 1,2, Yi-xin Zhou 1,2, Wei Wang 1,4, Wei-han Hu 1,3✉, Xiu-yu Cai 1,2✉

1. State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou
2. Department of VIP Region, Cancer Center, Sun Yat-Sen University, Guangzhou, China
3. Department of Radiation, Cancer Center, Sun Yat-Sen University, Guangzhou, China
4. Department of Gastric Surgery, Cancer Center, Sun Yat-Sen University, Guangzhou, China
5. Department of Pathology, Cancer Center, Sun Yat-Sen University, Guangzhou, China
6. Department of Radiology, The First People's Hospital of Foshan (The affiliated Foshan Hospital of Sun Yat-Sen University), Foshan, Guangdong, China
7. Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Science, Peking Union Medical College, Beijing 100021, China
#These authors have contributed equally to this work

Abstract

Background: DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is known to function in several types of cancer. In this study, we investigated the expression and clinicopathologic significance of DNA-PKcs in laryngeal squamous cell carcinoma (LSCC).

Methods: We conducted a retrospective study of 208 patients with advanced-stage LSCC treated at Sun Yat-sen University Cancer Center, Guangzhou, China. We assessed DNA-PKcs and p16INK4a (p16) status using immunohistochemistry. We examined the association between DNA-PKcs expression and clinicopathologic features and survival outcomes. To evaluate the independent prognostic relevance of DNA-PKcs, we used univariate and multivariate Cox regression models. We estimated overall survival (OS) and distant metastasis-free survival (DMFS) using the Kaplan-Meier method.

Results: Immunohistochemical analyses revealed that 163/208 (78.4%) of the LSCC tissue samples exhibited high DNA-PKcs expression. High DNA-PKcs expression was significantly associated with survival outcomes (P = 0.016) and distant metastasis (P = 0.02; chi-squared test). High DNA-PKcs expression was associated with a significantly shorter OS and DMFS than low DNA-PKcs expression (P = 0.029 and 0.033, respectively; log-rank test), and was associated with poor OS in the p16-positive subgroup (P = 0.047). Multivariate analysis identified DNA-PKcs as an independent prognostic indicator of OS and DMFS in all patients (P = 0.039 and 0.037, respectively).

Conclusions: Our results suggest that patients with LSCC in whom DNA-PKcs expression is elevated have a higher incidence of distant metastasis and a poorer prognosis. DNA-PKcs may represent a marker of tumor progression in patients with p16-positive LSCC.

Keywords: Laryngeal squamous cell carcinoma, DNA-dependent protein kinase catalytic subunit (DNA-PKcs), p16INK4a (p16), prognosis

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How to cite this article:
He Ss, Chen Y, Shen Xm, Wang Hz, Sun P, Dong J, Guo Gf, Chen Jg, Xia Lp, Hu Pl, Qiu Hj, Liu Ss, Zhou Yx, Wang W, Hu Wh, Cai Xy. DNA-dependent protein kinase catalytic subunit functions in metastasis and influences survival in advanced-stage laryngeal squamous cell carcinoma. J Cancer 2017; 8(12):2410-2416. doi:10.7150/jca.20069. Available from http://www.jcancer.org/v08p2410.htm