Overexpression of acylglycerol kinase is associated with poorer prognosis and lymph node metastasis in nasopharyngeal carcinoma
Overexpression of acylglycerol kinase is associated with poorer prognosis and lymph node metastasis in nasopharyngeal carcinoma
Qian Zhu 0 1
Su-Mei Cao 0 1
Huan-Xin Lin 0 1
Qi Yang 0 1
Sai-Lan Liu 0 1
Ling Guo 0 1
0 State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine , Guangzhou , China
1 Department of Preventive Oncology, Sun Yat-sen University Cancer Center , Guangzhou 510060, Guangdong , China
Acylglycerol kinase (AGK) has been reported to promote a malignant phenotype and enhance the development of cancer stem cells. However, the clinical value of AGK in cancer remains unclear. This study aimed to investigate the expression and clinicopathological significance of AGK in nasopharyngeal carcinoma (NPC). AGK was significantly upregulated in NPC cell lines and clinical specimens as indicated by real-time PCR and Western blotting. Among the AGKpositive cases, 52/114 (45.6 %) of the archived human NPC specimens expressed high levels of AGK. High expression of AGK was associated with significantly shorter overall and disease-free survival (P<0.001 and P =0.002; log-rank test) and was an independent prognostic factor for overall survival (P=0.041; multivariate Cox analysis). High AGK expression was associated with lymph node metastasis (P< 0.001; chisquared test) and was an independent predicted factor for lymph node metastasis in NPC (P= 0.032; multivariate logistic analysis). AGK is overexpressed and associated with disease progression and lymph node metastasis in NPC. AGK has potential as a novel prognostic factor for overall survival in NPC.
Acylglycerol kinase; Biomarker; Nasopharyngeal cancer; Lymph node metastasis; Prognosis
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Nasopharyngeal carcinoma (NPC) is a malignant cancer arising
from the epithelial surface of the nasopharynx. NPC is
especially common in Southern China and Southeast Asia [1, 2], with
the highest incidence in the world observed among the
Cantonese-speaking population in Guangdong Province [3,
4]. As a result of technical improvements in radiotherapy
delivery such as intensity-modulated radiation therapy (IMRT),
excellent local control can now be achieved; however, local
recurrence and metastasis remain the leading causes of mortality
in advanced stage disease [5]. Previous clinical study has
demonstrated that the neck nodal status is an independent
prognostic factor that affects overall survival in patients with NPC
without distant metastasis [6]. Involvement of both cervical lymph
nodes and retropharyngeal lymph nodes has prognostic value
for N1 patients with NPC [7]. Therefore, identification of
molecular markers for prognosis and lymph node metastasis may
help to improve the overall survival rate and design
individualized therapeutic regimens in patients with NPC.
Acylglycerol kinase (AGK) has been found to be
abundantly expressed in the heart, muscle, kidney, and brain [8].
By acting as a lipid kinase, AGK catalyzes the
phosphorylation of acylglycerol to generate lysophosphatidic acid (LPA)
[8–11], which is known to be involved in tumor progression
[12], invasion, neovascularization, and metastasis [13]. AGK
was reported to be overexpressed in prostate, breast,
esophageal squamous cell carcinoma (ESCC), and oral squamous
cell carcinoma [8, 14–17]. Bektas et al. demonstrated that
overexpression of AGK enhanced the proliferation and
migration of prostate cancer cells in vitro [8]. AGK expression was
significantly associated with the primary tumor Gleason grade
and prostatic capsular invasion in prostate cancer [14]. Wang
et al. showed that AGK promotes cell proliferation and
tumorigenicity in breast cancer [15]. Overexpression of AGK
promoted a stem cell-like phenotype in human ESCC cells
in vivo and tumorigenicity in vitro [16]. Recently, AGK is
reported to promote cell proliferation and cell cycle
progression in oral squamous cell carcinoma [17]. Taken together,
these findings indicate that AGK may play an essential role
in the progression and development of cancer. However, the
expression and clinical significance of AGK in NPC remain
unclear.
In the present study, we aimed to investigate the expression
of AGK in NPC and explore its relationship with the
clinicopathological features and prognosis of patients with NPC. We
demonstrate that AGK is significantly upregulated in NPC
and overexpression of AGK is closely associated with the
clinical stage, T, N, M classification, histological
differentiation, and lymph node metastasis. Moreover, Cox regression
analysis revealed that AGK may be considered as an
independent biomarker of prognosis in NPC. Multivariate logistic
analysis revealed that AGK may also represent an
independent biomarker for lymph node metastasis in NPC.
Collectively, these findings strongly suggest that AGK plays a
significant role in NPC progression and lymph node metastasis.
Materials and methods
The primary normal nasopharyngeal epithelial cell line NP69
was obtained from Dr. George SW Tsao, Cance (...truncated)