摘要目的 通过观察赖氨酸羟化酶2(PLOD2)在食管鳞状细胞癌(简称鳞癌)组织中的表达水平并分析其与临床病理参数间的相关性,探讨PLOD2调控食管鳞癌细胞侵袭转移的作用机制.方法 应用免疫组织化学法检测60例食管鳞癌患者(收集于2016年1月至2017年12月新乡医学院第一附属医院)肿瘤组织和配对癌旁组织中PLOD2的表达水平并分析其与临床病理参数的关系;应用天狼猩红染色检测胶原纤维蛋白沉积;LV-vector、LV-over/PLOD2慢病毒载体转染食管鳞癌细胞系EC-109细胞,应用即时荧光定量PCR法检测PLOD2表达情况;细胞迁移和侵袭实验检测肿瘤细胞迁移和侵袭能力;Western blot法检测PLOD2/AKT上皮-间质转化信号通路相关蛋白的表达.结果 在食管鳞癌患者肿瘤组织中PLOD2的表达水平(81.7％,49/60)显著高于配对癌旁组织(8.3％,5/60;P＜0.01);且与肿瘤浸润深度和淋巴结转移显著相关(P＜0.01);天狼猩红染色显示,PLOD2高表达的食管鳞癌组织中胶原纤维沉积显著高于PLOD2低表达的组织(P＜0.01);细胞迁移和侵袭实验结果显示,过表达PLOD2可提高EC-109细胞的迁移和侵袭能力,与LV载体组相比,差异有统计学意义(P＜0.01);Western blot结果显示,过表达PLOD2可上调黏着斑激酶(FAK)/AKT信号通路相关蛋白p-FAK、p-AKT、波形蛋白等的表达.结论 PLOD2在食管鳞癌组织中高表达,并与肿瘤迁移和侵袭密切相关;PLOD2促进食管鳞癌迁移和侵袭的机制可能与激活FAK/AKT信号通路、促进上皮-间质转化进程有关.

abstractsObjective To investigate PLOD2 expression in esophageal squamous cell carcinoma,and to explore the potential mechanism by which PLOD2 promotes tumor metastasis.Methods The expression of PLOD2 in 60 cases of esophageal squamous cell carcinoma (the patients were collected at the first Affiliated Hospital of Xinxiang Medical University,from January 2016 to December 2017) was investigated by immunohistochemistry.Fibrillar collagen formation and collagen deposition were detected by picrosirius red staining.Correlation of PLOD2 expression with clinical pathologic features of the patients was performed using X2 test and Kaplan-Meier analysis.After EC-109 cells were transfected with LV-vector and LV-over/PLOD2,the expression of PLOD2 was detected by real time PCR and the impact of POLD2 on invasion in EC-109 cells was determined by transwell migration and invasion assays.The expression of PLOD2/AKT epithelial-to-mesenchymal transition signal pathway related proteins was detected by Western blot.Results The expression level of PLOD2 in esophageal squamous cell carcinoma was 81.7％ (49/60 cases),higher than their paired noncancerous tissues(8.3％,5/60;P＜0.01),and correlated significantly with tumor depth of invasion and nodal metastasis(P＜0.01).Picrosirius red staining showed that collagen deposition was increased and the degree of fibrillar organization was enhanced in carcinoma tissues that had higher PLOD2 expression.Transwell migration and invasion assays showed that PLOD2 significantly promoted the migration and invasion ability of EC-109 cells.Western blot showed that PLOD2 significantly increased the expression levels of p-FAK,p-AKT and vimentin in EC-109 cells.Conclusions Esophageal squamous cell carcinoma has a high expression of PLOD2 that correlates with tumor invasion and lymph node metastasis.PLOD2 promotes invasion and metastasis of esophageal squamous cell carcinoma through epithelial-to-mesenchymal transition via FAK/AKT signal pathway.