J Cancer 2017; 8(17):3548-3554. doi:10.7150/jca.20535

Research Paper

Loss of LKB1 Expression Decreases the Survival and Promotes Laryngeal Cancer Metastasis

Sha-sha He1, 3*, Yong Chen1, 3*, Hong-zhi Wang7*, Xiao-ming Shen1, 6, Peng Sun1, 5, Jun Dong1, 2, Xin-biao Liao8, Gui-fang Guo1, 2, Ju-gao Chen1, Liang-ping Xia1, 2, Pei-li Hu1, 2, Hui-juan Qiu1, 2, Shou-sheng Liu1, 2, Yi-xin Zhou1, 2, Wei Wang1, 4, Wei-han Hu1, 3✉, Xiu-yu Cai1, 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;
8. Department of Radiation Oncology, The First Affiliated Hospital of Zhejiang University, Hangzhou, China.
* These authors have contributed equally to this work

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
He Ss, Chen Y, Wang Hz, Shen Xm, Sun P, Dong J, Liao Xb, Guo Gf, Chen Jg, Xia Lp, Hu Pl, Qiu Hj, Liu Ss, Zhou Yx, Wang W, Hu Wh, Cai Xy. Loss of LKB1 Expression Decreases the Survival and Promotes Laryngeal Cancer Metastasis. J Cancer 2017; 8(17):3548-3554. doi:10.7150/jca.20535. Available from http://www.jcancer.org/v08p3548.htm

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Background: Given recent results indicating that diminished LKB1 expression in laryngeal cancer correlates with shorter survival. We aim to perform an analysis estimate the role of decreased liver kinase B1(LKB1) and in the prognostication of human laryngeal squamous cell carcinoma (LSCC).

Methods: We conducted a retrospective study and evaluate the expression of LKB1 and p16INK4a (p16) in 208 clinical advanced-stage LSCC tissue samples by using immunohistochemistry. The specimens were received at Sun Yat-sen University Cancer Center (Guangzhou, China). To evaluate the independent prognostic relevance of LKB1, univariate and multivariate Cox regression models were used, overall survival (OS) and distant metastasis-free survival (DMFS) were compared using the Kaplan-Meier method.

Results: Immunohistochemical analyses revealed that 80/208 (38.5%) of the LSCC tissue samples expressed high LKB1. Low LKB1 expression was associated with a significantly shorter OS and DMFS than high LKB1 expression (P = 0.041 and 0.028, respectively; log-rank test), and there was a poorer OS in the p16-positive than p16-negative group. In the subgroup stratified by p16 status, the shorter OS were also seen with low LKB1 expression. Multivariate survival analysis indicated that high LKB1 expression was an independent prognostic factor for OS (hazard ratio [HR]: 1.628, 95% confidence interval [CI]: 1.060-2.500, P = 0.026) and DMFS (HR: 2.182, 95% CI: 1.069-4.456, P = 0.032).

Conclusions: Our data indicated that low expression of LKB1 was significantly associated with poor prognosis and it may represent a marker of tumor metastasis in patients with LSCC. When combined with p16, LKB1 was also of prognostic value.

Keywords: Laryngeal squamous cell carcinoma, liver kinase B1 (LKB1), p16INK4a (p16), prognosis.