Overexpression of acylglycerol kinase is associated with poorer prognosis and lymph node metastasis in nasopharyngeal carcinoma

Tumor Biology, Oct 2015

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 AGK-positive 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; chi-squared 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.

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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 - 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)


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Qian Zhu, Su-Mei Cao, Huan-Xin Lin, Qi Yang, Sai-Lan Liu, Ling Guo. Overexpression of acylglycerol kinase is associated with poorer prognosis and lymph node metastasis in nasopharyngeal carcinoma, Tumor Biology, 2016, pp. 3349-3357, Volume 37, Issue 3, DOI: 10.1007/s13277-015-4148-x