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. 2017 Sep 30;8(17):3548-3554.
doi: 10.7150/jca.20535. eCollection 2017.

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

Sha-Sha He  1   2 , Yong Chen  1   2 , Hong-Zhi Wang  3 , Xiao-Ming Shen  1   4 , Peng Sun  1   5 , Jun Dong  1   6 , Xin-Biao Liao  7 , Gui-Fang Guo  1   6 , Ju-Gao Chen  1 , Liang-Ping Xia  1   6 , Pei-Li Hu  1   6 , Hui-Juan Qiu  1   6 , Shou-Sheng Liu  1   6 , Yi-Xin Zhou  1   6 , Wei Wang  1   8 , Wei-Han Hu  1   2 , Xiu-Yu Cai  1   6
Affiliations

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

Sha-Sha He et al. J Cancer. .

Abstract

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..

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
p16 and LKB1 overexpression in larynx tumors. Same region of same tumor staining positive for p16 (cytoplasm) and DNA-PKcs (cytoplasm), With magnification of 200× and 400×.
Figure 2
Figure 2
Kaplan-Meier overall survival (A) and distant metastasis-free survival (B) curves for 208 patients with laryngeal squamous cell carcinoma stratified by LKB1 expression.
Figure 3
Figure 3
Kaplan-Meier overall survival (A) and distant metastasis-free survival (B) curves for 208 patients with laryngeal squamous cell carcinoma stratified by p16 expression.
Figure 4
Figure 4
Kaplan-Meier overall survival (A) and distant metastasis-free survival (B) curves for patients with p16 positive; overall survival (C) and distant metastasis-free survival (D) curves for patients with p16 negative.
See this image and copyright information in PMC

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