SPNS2和Lgr5在喉鳞状细胞癌中的表达及其与预后的相关性

doi:10.3760/cma.j.issn.1673-422X.2020.03.002

摘要/Abstract

摘要：

目的探讨鞘氨醇-1-磷酸转运体2(SPNS2)和富含亮氨酸重复单位的G蛋白偶联受体5(Lgr5)在喉鳞状细胞癌中的表达及其与临床病理特征和预后的关系。方法收集2012年3月至2016年3月江苏省泰兴市人民医院82例喉鳞状细胞癌患者术后石蜡标本,采用免疫组织化学法检测82例癌组织及50例癌旁正常组织中SPNS2、Lgr5的表达状态,分析SPNS2、Lgr5的表达与患者临床病理特征及预后的关系。结果喉鳞状细胞癌组织SPNS2高表达率为40.24%(33/82),高于癌旁正常组织的8.00%(4/50),癌组织Lgr5高表达率为46.34%(38/82),高于癌旁正常组织的12.00%(6/50),差异均有统计学意义(χ ²=16.008,P<0.001;χ ²=16.484,P<0.001)。SPNS2表达状态与肿瘤大小(χ ²=5.713,P=0.017)、肿瘤分期(χ ²=7.071,P=0.008)、肿瘤分化程度(χ ²=5.722,P=0.017)及淋巴结转移(χ ²=6.595,P=0.010)有关。Lgr5表达状态与肿瘤分期(χ ²=8.200,P=0.004)、肿瘤分化程度(χ ²=9.435,P=0.002)以及淋巴结转移(χ ²=16.188,P<0.001)有关。SPNS2低表达组患者的3年总生存率为90.91%,显著高于SPNS2高表达组的71.43%(χ ²=4.975,P=0.026)。SPNS2低表达组患者的3年无进展生存率为78.79%,显著高于SPNS2高表达组的55.10%(χ ²=6.113,P=0.013)。Lgr5低表达组患者的3年总生存率为86.84%,显著高于Lgr5高表达组的65.91%(χ ²=5.801,P=0.016);Lgr5低表达组患者的3年无进展生存率为78.95%,显著高于Lgr5高表达组的56.82%(χ ²=6.316,P=0.012)。多因素Cox回归分析显示,分化程度(RR=0.199,95%CI为0.057~0.691,P=0.011)、肿瘤分期(RR=0.167,95%CI为0.053~0.531,P=0.002)、SPNS2(RR=0.208,95%CI为0.072~0.604,P=0.004)、Lgr5(RR=0.198,95%CI为0.060~0.655,P=0.008)是影响喉鳞状细胞癌患者预后的危险因素。列联相关分析显示,SPNS2和Lgr5在喉鳞状细胞癌组织中的表达呈正相关(C=0.591,P<0.001)。结论 SPNS2和Lgr5在喉鳞状细胞癌组织中显著高表达,与临床病理特征密切相关,且二者均是影响喉鳞状细胞癌患者预后的危险因素。

关键词: 喉肿瘤, 病理学, 预后, 鞘氨醇-1-磷酸转运体2, 富含亮氨酸重复序列G-蛋白偶联受体5

Abstract:

Objective To investigate the expressions of sphingosine-1-phosphate transporter 2 (SPNS2) and leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) in laryngeal squamous cell carcinoma and their correlations with clinicopathological features and prognosis. Methods A total of 82 cases of squamous cell carcinoma were collected from the paraffin-embedded specimens of laryngeal cancer in Taixing People's Hospital of Jiangsu Province from March 2012 to March 2016. The expressions of SPNS2 and Lgr5 were detected by immunohistochemistry in 82 cancerous tissues and 50 adjacent normal tissues. The relationships between the expressions of SPNS2 and Lgr5 in patients with laryngeal squamous cell carcinoma and clinicopathological features and prognosis were analyzed. Results The high expression rate of SPNS2 in laryngeal squamous cell carcinoma tissues was 40.24% (33/82), which was higher than 8.00% (4/50) in normal tissues adjacent to cancer. The high expression rate of Lgr5 in cancerous tissues was 46.34% (38/82), which was higher than 12.00% (6/50) in normal tissues adjacent to cancer. The differences were statistically significant (χ ²=16.008, P<0.001; χ ²=16.484, P<0.001). The expression status of SPNS2 was related to tumor size (χ ²=5.713, P=0.017), tumor stage (χ ²=7.071, P=0.008), tumor differentiation degree (χ ²=5.722, P=0.017) and lymph node metastasis (χ ²=6.595, P=0.010). There were significant differences in the expression status of Lgr5 in different tumor stage (χ ²=8.200, P=0.004), tumor differentiation (χ ²=9.435, P=0.002) and lymph node metastasis (χ ²=16.188, P<0.001). The 3-year overall survival rate of patients in SPNS2 low expression group was 90.91%, which was higher than that of patients in SPNS2 high expression group (71.43%, χ ²=4.975, P=0.026). The 3-year progression-free survival rate of patients in SPNS2 low expression group was 78.79%, which was higher than that of patients in SPNS2 high expression group (55.10%, χ ²=6.113, P=0.013). The 3-year overall survival rate of patients in Lgr5 low expression group was 86.84%, which was higher than that of patients in Lgr5 high expression group (65.91%, χ ²=5.801, P=0.016). The 3-year progression-free survival rate of patients in Lgr5 low expression group was 78.95%, which was higher than that of patients in Lgr5 high expression group (56.82%, χ ²=6.316, P=0.012). Multivariate Cox regression analysis showed that differentiation (RR=0.199, 95%CI: 0.057-0.691, P=0.011), tumor staging (RR=0.167, 95%CI: 0.053-0.531, P=0.002), SPNS2 (RR=0.208, 95%CI: 0.072-0.604, P=0.004) and Lgr5 (RR=0.198, 95%CI: 0.060-0.655, P=0.008) were risk factors for the prognosis of patients with laryngeal squamous cell carcinoma. Contingency correlation analysis showed a positive correlation between SPNS2 and Lgr5 expressions in laryngeal squamous cell carcinoma (C=0.591, P<0.001). Conclusion SPNS2 and Lgr5 are highly expressed in laryngeal squamous cell carcinoma and are closely related to clinicopathological features. And SPNS2 and Lgr5 are risk factors for the prognosis of patients with laryngeal squamous cell carcinoma.

Key words: Laryngeal neoplasms, Pathology, Prognosis, Sphingosine-1-phosphate transporter 2, Leucine-rich repeat-containing G-protein coupled receptor 5

王晓军, 曹鹏, 朱新华. SPNS2和Lgr5在喉鳞状细胞癌中的表达及其与预后的相关性[J]. 国际肿瘤学杂志, 2020, 47(3): 135-140.

Wang Xiaojun, Cao Peng, Zhu Xinhua. Expressions of SPNS2 and Lgr5 in laryngeal squamous cell carcinoma and their correlations with prognosis[J]. Journal of International Oncology, 2020, 47(3): 135-140.

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变量	β值	SE值	Wald值	P值	RR值(95%CI)
年龄	0.786	0.511	2.365	0.124	0.456(0.167~1.241)
性别	0.067	0.488	0.019	0.891	0.935(0.360~2.433)
分化程度	1.717	0.640	7.199	0.007	5.568(1.588~19.520)
肿瘤部位	0.447	0.802	0.311	0.577	1.564(0.325~7.532)
肿瘤大小	1.767	0.577	9.387	0.002	0.171(0.055~0.529)
肿瘤分期	1.971	0.755	6.804	0.009	0.139(0.032~0.613)
淋巴结转移	0.552	0.508	1.182	0.277	0.576(0.213~1.558)
SPNS2状态	1.687	0.538	9.850	0.002	0.185(0.064~0.531)
Lgr5状态	1.454	0.513	8.043	0.005	0.234(0.086~0.638)

变量	β值	SE值	Wald值	P值	RR值(95%CI)
分化程度	1.616	0.636	6.456	0.011	0.199(0.057~0.691)
肿瘤大小	0.929	0.592	2.466	0.116	0.395(0.124~1.259)
肿瘤分期	1.790	0.590	9.196	0.002	0.167(0.053~0.531)
SPNS2状态	1.569	0.543	8.353	0.004	0.208(0.072~0.604)
Lgr5状态	1.617	0.609	7.053	0.008	0.198(0.060~0.655)