Wang Qiushi, Li Jingyuan, Li Guanghua, Li Yinghong, Xu Chunlin, Li Ming, Xu Guangquan, Fu Songbin
Department of Cardiothoracic Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, 150086, China.
Tumour Biol. 2014 Jan;35(1):363-8. doi: 10.1007/s13277-013-1051-1. Epub 2013 Aug 7.
Sphingosine kinase 2 (SphK2) as a conserved lipid kinase has not been thoroughly elucidated in non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate the expression of SphK2 in NSCLC tissues and to determine its correlation with clinicopathologic characteristics and its impact on patient prognosis. We assessed the expression of SphK2 and proliferating cell nuclear antigen (PCNA) (as a proliferative index) by immunohistochemistry in 180 NSCLC patient's formalin-fixed paraffin-embedded tissue blocks. Relationship between the expression of SphK2 and PCNA and various clinicopathological features in these patients was evaluated. We detected that expression of SphK2 was gradually upregulated from normal, metaplasia/dysplasia tissues to NSCLC tissues. At the same time, PCNA expression followed a similar pattern. Statistical analysis showed that expression of SphK2 in NSCLC tissues was strongly associated with PCNA expression, histology grade, live vaccine strain invasion, lymph node status, clinical stage, tumors size, and histology type. Patients with SphK2 overexpression in their tissues had lower overall survival (OS) and disease-free survival (DFS) rates than those with low SphK2 expression. Using uni- and multivariate analysis, we found that SphK2 overexpression was an independent prognostic factor for both OS and DFS. The expression of SphK2 parallels the progression of NSCLC, and SphK2 overexpression may represent a novel and potentially independent biomarker for the prognosis of patients with NSCLC.
鞘氨醇激酶2（SphK2）作为一种保守的脂质激酶，在非小细胞肺癌（NSCLC）中的作用尚未完全阐明。本研究旨在评估SphK2在NSCLC组织中的表达，并确定其与临床病理特征的相关性及其对患者预后的影响。我们通过免疫组织化学方法评估了180例NSCLC患者福尔马林固定石蜡包埋组织块中SphK2和增殖细胞核抗原（PCNA）（作为增殖指数）的表达。评估了SphK2和PCNA的表达与这些患者各种临床病理特征之间的关系。我们检测到，从正常组织、化生/发育异常组织到NSCLC组织，SphK2的表达逐渐上调。同时，PCNA的表达也呈现类似模式。统计分析表明，NSCLC组织中SphK2的表达与PCNA表达、组织学分级、活疫苗株侵袭、淋巴结状态、临床分期、肿瘤大小和组织学类型密切相关。组织中SphK2过表达的患者总生存期（OS）和无病生存期（DFS）率低于SphK2低表达的患者。通过单因素和多因素分析，我们发现SphK2过表达是OS和DFS的独立预后因素。SphK2的表达与NSCLC的进展平行，SphK2过表达可能代表一种新的、潜在的独立生物标志物，用于预测NSCLC患者的预后。
