LETM1蛋白在三阴性乳腺癌组织中的表达及与患者临床特征和预后的关系

Expression of LETM1 in cancer tissues of triple negative breast cancer and its relationship with clinical features and prognosis of these patients

目的探讨亮氨酸拉链EF-hand结构域跨膜蛋白1(LETM1)在三阴性乳腺癌(TNBC)组织中的表达及与患者临床特征和预后的关系。方法选取100例TNBC患者的TNBC组织标本,另选取同期100例导管原位癌患者的导管内原位癌组织标本及其癌旁正常组织标本。采用免疫组织化学法检测各组织中LETM1蛋白的表达情况,分析LETM1蛋白表达与TNBC患者临床特征及预后的关系。结果 TNBC组织中LETM1蛋白的阳性表达率高于导管内原位癌组织和癌旁正常组织(P﹤0.05),导管内原位癌组织中LETM1蛋白的阳性表达率高于癌旁正常组织(P﹤0.05)。组织学分级为Ⅱ～Ⅲ级、临床分期为Ⅲ期、有淋巴结转移的TNBC患者的LETM1蛋白中等-强阳性表达率均高于组织学分级为Ⅰ级、临床分期为Ⅰ～Ⅱ期、无淋巴结转移的患者,差异均有统计学意义(P﹤0.05);不同年龄、绝经状态、肿瘤直径和p53表达情况的TNBC患者的LETM1蛋白中等-强阳性表达率比较,差异均无统计学意义(P﹥0.05)。单因素分析结果显示,年龄≥50岁、绝经后、组织学分级为Ⅱ～Ⅲ级、有淋巴结转移、LETM1蛋白表达为中等-强阳性的TNBC患者的中位总生存时间(OS)均短于年龄﹤50岁、绝经前、组织学分级为Ⅰ级、无淋巴结转移、LETM1蛋白表达为阴性+弱阳性的TNBC患者,差异均有统计学意义(P﹤0.05)。多因素分析结果显示,淋巴结转移和LETM1蛋白强阳性表达是影响TNBC患者OS的独立危险因素(P﹤0.05)。结论LETM1蛋白可作为临床上判断TNBC恶性程度的指标,是影响TNBC患者预后的独立危险因素,可作为TNBC预后预测的指标,有望成为TNBC潜在的生物学指标及治疗靶点。

Objective To investigate the expression of leucine zipper/EF-hand-containing transmembrane protein 1（LETM1） in cancer tissues of triple negative breast cancer（TNBC） and its relationship with clinical features and prognosis of TNBC patients. Method One hundred specimens of TNBC tissues were collected, during the same period, another100 specimens of tumor tissues and 100 specimens of adjacent normal tissues in ductal cancer in situ were also collected.The expression of LETM1 in these tissues were analyzed by immunofluorescence staining, and the relationship between the expression of LETM1 protein and clinical features and prognosis of TNBC patients were analyzed. Result The positive expression rate of LETM1 protein in TNBC tissues were significantly higher than that in tumor tissues and adjacent normal tissues in ductal cancer in situ（P〈0.05）, and in ductal cancer in situ tissues, higher positive expression rate of LETM1 protein was observed in tumor tissues than in adjacent normal tissues（P〈0.05）. In the comparison between TNBC patients with histological grade Ⅱ-Ⅲ and clinical stage Ⅲ disease, and positive lymph node metastasis versus those with histological grade I and clinical stage Ⅰ-Ⅱ disease, and negative lymph node metastasis, the moderate-high LETM1 positive expression rate was higher in the former subgroup, showing statistically significant difference（P〈0.05）; while there was no significant difference in the moderate-high LETM1 positive expression rate in TNBC patients with varied age, menopausal stage, tumor diameter and p53 expression, and the difference was of no statistical significance（P〉0.05）.Univariate analysis showed that, in TNBC patients with age ≥50, who were post-menopausal, with histological grade Ⅱ-Ⅲ disease, and positive lymph node metastasis, LETM1 protein expression of moderate-high positive, the median overall survival（OS） were shorter than those with age 50, who were pre-menopausal, with histological grade I disease, negativelymph node metastasis, and LETM1 protein expression of negative and weak positive, and the differences were statistically significant（P〈0.05）. Multivariate regression analysis indicated that lymph node metastasis and LETM1 protein expression of strongly positive were independent risk factors for the OS of patients with TNBC（P〈0.05）. Conclusion LETM1 protein can be used as an indicator of the malignancy of TNBC, and is an independent risk factor, yet a predictor for the prognosis of patients with TNBC, and is expected to become a potential biomarker and therapeutic target for TNBC patients.