线粒体肿瘤抑制基因1在舌鳞状细胞癌组织中的表达及意义

Expression and significance of mitochondrial tumor suppressor gene 1 in tongue cell carcinoma

目的探讨线粒体肿瘤抑制基因1(MTUS1)在舌鳞状细胞癌(TSCC)中的表达及其临床意义。方法应用免疫组织化学检测80例TSCC、27例舌白斑和13例正常舌黏膜中MTUS1的表达,并对其表达水平进行统计学分析。定量反转录聚合酶链反应(RT-PCR)检测正常舌黏膜与TSCC中MTUS1亚型的表达水平并进行统计学分析。Kapalan-Meier法分析TSCC患者生存率,并统计分析MTUS1在TSCC中的表达与生存率之间的关系。SPSS 13.0统计软件分析数据。结果在正常舌黏膜上皮中MTUS1主要表达于棘层细胞胞浆内,部分位于胞核。正常舌黏膜中MTUS1的表达水平明显高于舌白斑(t=5.876,P=0.037)和TSCC(t=7.638,P=0.000 83);舌白斑中MTUS1的表达明显高于TSCC,其差异有统计学意义(t=5.281,P=0.0042)。MTUS1在高分化TSCC组织中的表达高于中分化和低分化者,但表达差异无统计学意义(F=1.873,P=0.071)。定量RT-PCR检测显示,ATIP1、ATIP3a和ATIP3b是舌黏膜组织中MTUS1/ATIP的主要亚型;与正常舌黏膜相比,TSCC组织中MTUS1/ATIP亚型的表达明显降低,差异有统计学意义(t=5.627,P=0.0153)。高表达MTUS1的TSCC患者生存率明显高于低表达者(F=5.876,P=0.0286)。结论MTUS1在TSCC的发生、发展中起着重要作用。

Objective To investigate the significance of MTUS1 in tongue cell carcinoma. Methods Immunohistochemical staining was applied to quantify the expression levels of MTUS1 in 80 cases of tongue cell carcinoma, 27 cases of tongue leukoplakia, 13 cases of normal tongue mucosa. The expression of MTUS1/ATIP isofoms were determined in normal tongue tissue and tongue cell carcinoma tissue using MTUS1/ATIP isofom specific quantitative RT-PCR assays. Survival analysis was performed using the Kaplan-Meier analysis in patients with squamous cell carcinoma of the tongue, and detect the relationship between the expression of MTUS1 and survival in tongue squamous cell carcinoma. Statistical analysis was done with SPSS 13.0. Results MTUS1 staining was detected in cytoplasm of stratum spinosum in normal tongue mucosa, partially located in the nucles. The staining intensity of MTUS1 was higher in normal tongue mucosa than in tongue squamous cell carcinoma （t = 7.638,P = 0.000 83） and in tongue leukoplakia （t = 5.876,P = 0.037）; the expression of MTUS1 was significantly higher in tongue leukoplakia than tongue squamous cell carcinoma, differences were statistical significance （t = 5.281,P = 0.0042）. There was a significant reduction in MTUS1/ATIP levels of moderately and poorly differentiated OTSCC, compared to well-differentiated OTSCC cases, but the staining intensity of MTUS1 was no significant difference in the degree of differentiation （F = 1.873,P = 0.071）. Isoform specific quantitative RT-PCR assays revealed that ATIP1, ATIP3a and ATIP3b were the major isoforms of the MTUS1 gene products in oral tongue epithelial. There was a significant reduction of MTUS1/ATIP expression in tongue squamous cell carcinoma, as compared with the normal tongue mucosa. The high expression of MTUS1 survival with tongue squamous cell carcinoma was significantly higher than the low expression（F = 5.876,P = 0.0286）. Conclusion MTUS1 plays an important role in the development of tongue squamous cell carcinoma.