食管鳞状细胞癌中FBXO32基因表达及其临床意义

Expression of FBXO32 in esophageal squamous cell carcinoma and its clinical significance

目的观察食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)中FBXO32基因的表达,探讨该基因在ESCC发生、发展中的作用。方法分别应用RT-PCR及免疫组织/细胞化学法检测食管癌细胞和ESCC组织中FBXO32 mRNA及蛋白表达,观察DNA去甲基化剂5-氮杂-2'-脱氧胞苷(5-aza-2'-deoxycitydine,5-aza-dC)对食管癌细胞系(TE1、TE13、T.TN、Yes-2)FBXO32基因表达的影响。结果 TE13、T.TN、Yes-2细胞株中均未检测到FBXO32 mRNA及蛋白表达,在去甲基化剂作用后,4株食管癌细胞株中FBXO32基因表达均上调。FBXO32 mRNA在ESCC和癌旁正常组织中的表达量分别为0.24±0.15和0.49±0.21,ESCC组织中FBXO32 mRNA表达量明显低于癌旁正常组织(P<0.05),且与患者的淋巴结转移及肿瘤组织的分化程度密切相关。51例ESCC组织中,12例FBXO32基因蛋白表达,阳性率为23.5%,明显低于正常食管黏膜组织(70.5%,P<0.01),且FBXO32与患者的淋巴结转移密切相关。结论 FBXO32基因在ESCC中的异常低表达与ESCC的发生、发展密切相关,且甲基化可能是其表达沉默的机制之一。

Purpose To investigate the expression status and the role of FBXO32 （also called atrogin-1 ） in esophageal squamous cell carcinoma （ESCC）. Methods Reverse transcription-polymerase chain reaction （RT-PCR） and immunohistochemieal/immunoeyto- chemical staining were used respectively to detect mRNA and protein expression of FBXO32 gene in esophageal cancer cell lines and tissues of ESCC. DNA methyltransferase inhibitor 5-aza-2＇-detoxycytidine （5-aza-dC） was used to observe its effect on esophageal cancer cell lines （TEl, TEl3, T. TN, Yes-2）. Results mRNA and protein expression of FBXO32 was not detected in the three e- sophageal cancer cell lines （TEl3, T. TN, and Yes-2）. Demethylation agent 5-aza-dC successfully enhanced FBXO32 expression in the three cell lines, mRNA expression of FBXO32 in esophageal squamous cell carcinoma （0. 24 -＋ 0. 15 ） was significantly lower than that in corresponding normal tissues （0.49 -＋ 0. 21 ） （P 〈 0. 05 ） and was associated with the lymph node metastasis and histological differentiation of ESCC patients. Positive protein expression of FBXO32 in tumor tissues （23.5%） was significantly lower than that in corresponding normal tissues （70. 5% ） （ P 〈0. 01 ） and was associated with lymph node metastasis of ESCC patients. Conclusions Aberrant low expression of FBXO32 is closely related to the development and occurrence of ESCC, and DNA methylation may be one of the mechanisms for inactivation of FBXO32 in esophageal squamous cell carcinoma.