SLC5A12在食管鳞癌中表达的临床意义及其对食管鳞癌细胞恶性表型的影响

Clinical significance of SLC5A12 expression in esophageal squamous cell carcinoma and its effect on malig⁃nant phenotype of esophageal squamous cell carcinoma

目的通过蛋白质谱测序筛选与食管鳞癌(esophageal squamous cell carcinoma,ESCC)预后相关基因SLC5A12并探讨其对ESCC细胞恶性表型的影响。方法蛋白质谱测序筛选在ESCC中差异表达的蛋白质,公共数据库筛选差异蛋白中与ESCC预后相关的基因SLC5A12并分析数据库中ESCC患者SLC5A12表达与预后的关系。对生物样本库中随访信息完善的117例ESCC患者配对的肿瘤及正常组织制作的组织芯片进行免疫组织化学染色,分析SLC5A12在ESCC中的表达及其与患者临床病理和预后的关系。小干扰RNA敲减ESCC细胞中SLC5A12表达,检测细胞的增殖、侵袭及迁移能力。结果ESCC中共有235个蛋白质表达上调,362个蛋白质表达下调,其中SLC5A12表达显著高于正常组织(log2 fold=1.33,P=0.0004)。TCGA中ESCC患者SLC5A12表达显著高于正常组织及食管腺癌,且N分期及SLC5A12表达是患者生存的风险因素,SLC5A12表达与ESCC患者总生存[HR=2.74,95%CI:1.27~5.94,P=0.012]及疾病特异性生存[HR=3.14,95%CI:1.24~7.95,P=0.02]显著相关。组织芯片免疫组织化学染色结果证实,SLC5A12在ESCC中表达显著高于正常组织,且在淋巴结转移患者中显著高于未转移者。SLC5A12表达水平与ESCC患者总生存期(P<0.0001)、病理分期(P<0.001)及淋巴结转移(P<0.001)显著相关。敲减SLC5A12表达后,ESCC细胞的增殖、侵袭及迁移能力均显著降低。结论SLC5A12在ESCC中表达显著高于正常组织且与患者的预后、病理分期及淋巴结转移显著相关,SLC5A12能够促进ESCC细胞的恶性表型进展。

Objective To screen the prognosis⁃related gene SLC5A12 of esophageal squamous cell carcinoma by protein profiling and explore its effect on the malignant phenotype of ESCC cells.Methods Protein profiling was performed to screen for differentially expressed proteins in ESCC,and public databases were used to screen for SLC5A12,a gene associated with prognosis in ESCC,and to analyze the relationship between SLC5A12 expression and prognosis in ESCC patients in the database.Immunohistochemical staining of tissue microarrays made from paired tumor and normal tissues of 117 ESCC patients with perfect follow⁃up information in the biospeci⁃men database was performed to analyze the expression of SLC5A12 in ESCC and its relationship with the clinicopa⁃thology and prognosis of patients.Small interfering RNA knocked down the expression of SLC5A12 in ESCC cells,and the proliferation,invasion and migration ability of the cells were detected.Results A total of 235 protein expressions were upregulated and 362 protein expressions were downregulated in ESCC,in which SLC5A12 expres⁃sion was significantly higher than that in normal tissues(log2 fold=1.33,P=0.0004).SLC5A12 expression in ESCC patients in TCGA was significantly higher than that in normal tissues and esophageal adenocarcinoma,and N stage and SLC5A12 expression were risk factors for patient survival factors,and SLC5A12 expression was signifi⁃cantly associated with overall survival[HR=2.74,95%CI:1.27~5.94,P=0.012]and disease⁃specific survival[HR=3.14,95%CI:1.24~7.95,P=0.02]in ESCC patients.Immunohistochemical staining of tissue microarrays confirmed that SLC5A12 expression was significantly higher in ESCC than in normal tissues and significantly higher in patients with lymph node metastases than in those without metastases.SLC5A12 expression levels were signifi⁃cantly correlated with overall survival(P<0.0001),pathological stage(P<0.001)and lymph node metastases(P<0.001)in ESCC patients.The proliferation,invasion and migration ability of ESCC cells were significantly reduced after knockdown of SLC5A12 expression.Conclusions SLC5A12 expression in ESCC was significantly higher than that in normal tissues and significantly correlated with the prognosis,pathological stage and lymph node metastasis of patients,and SLC5A12 could promote the malignant phenotype progression of ESCC cells.