非小细胞肺癌中FtMt蛋白的表达水平及其临床病理意义

Expression of FtMt Protein in Non-small Cell Lung Cancer and Its Clinicopathological Significance

目的研究非小细胞肺癌(non-small cell lung cancer,NSCLC)中线粒体铁蛋白(mitochondrial ferritin,FtMt)表达与临床病理和分子特征的相关性。方法选择2018年9月~2020年12月期间经病理确诊为NSCLC的手术切除标本154例,采用免疫组化方法检测FtMt的蛋白表达,采用扩增阻滞突变系统检测EGFR、ALK、KRAS基因突变,采用荧光定量PCR检测上皮间质转化标志物N-钙黏蛋白(N-cadherin)、E-钙黏蛋白(E-cadherin)、波形蛋白(Vimentin)、线粒体途径凋亡蛋白B淋巴细胞瘤-2(Bcl-2)、Bcl2相关X蛋白(Bcl2-associated X,Bax)、含半胱氨酸的天冬氨酸蛋白水解酶-3(Caspase-3)、铁死亡标志物谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)、胱氨酸/谷氨酸逆向转运蛋白溶质载体家族7成员11(solute carrier family 7 member 11,SLC7A11)的mRNA表达水平。随访NSCLC患者的无瘤生存和总生存情况。结果NSCLC组织中FtMt的阳性表达率高于癌旁组织(P<0.05);低分化、pTNMⅢ期、有淋巴结转移的NSCLC组织中FtMt阳性表达率高于高分化、pTNMⅠ~Ⅱ期、无淋巴结转移的NSCLC(P<0.05);与FtMt阴性表达的NSCLC组织比较,FtMt阳性表达的NSCLC组织中N-cadherin、Vimentin、Bcl-2、GPX4、SLC7A11的mRNA表达水平及EGFR突变率升高,E-cadherin、Bax、Caspase-3的mRNA表达水平及无瘤生存率、总生存率均降低(P<0.05)。结论NSCLC中FtMt阳性表达与病理进展、EGFR突变及生存率降低有关,与之相关的生物学机制可能是异常的上皮间质转化、铁死亡、线粒体途径凋亡。

Objective To study the relationships between the expression level of mitochondrial ferritin(FtMt)and the clinical pathology and molecular characteristics in non-small cell lung cancer(NSCLC).Methods A total of 154 surgical specimens with pathologically confirmed NSCLC from September 2018 to December 2020 were selected.Immunohistochemistry was used to determine the expression of FtMt protein.Amplification refractory mutation system was used to detect the mutations of EGFR,ALK,and KRAS genes.Fluorescence quantitative PCR was used to detect the mRNA expression levels of epithelial-mesenchymal transformation markers N-cadherin,E-cadherin,Vimentin,and mitochondrial pathway apoptotic proteins B-lymphoblastoma-2(Bcl-2),Bcl2-associated X-protein(Bax),caspase-3,and ferroptosis markers glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11).Patients with NSCLC were followed-up for the tumor free survival and overall survival.Results The positive expression rate of FtMt in the NSCLC tissues was higher than that in the adjacent tissues(P<0.05).The positive expression rates of FtMt in NSCLC tissues with low differentiation,pTNM stageⅢ,and lymph node metastasis were higher than those with high differentiation,pTNM stageⅠ-Ⅱ,and no lymph node metastasis(P<0.05).The mRNA expression levels of N-cadherin,Vimentin,Bcl-2,GPX4,SLC7A11 and the mutant rate of EGFR in the NSCLC tissues with positive FtMt expression were increased,while the mRNA expression levels of E-cadherin,Bax,and Caspase-3,as well as the tumor free survival rate and overall survival rate were decreased when compared with those in the NSCLC tissues with negative FtMt expressions(P<0.05).Conclusion The positive expression of FtMt in NSCLC is associated with pathological progression,EGFR mutation,and reduced survival.The biological mechanisms may associate with abnormal epithelial mesenchymal transformation,ferroptosis and mitochondrial pathway apoptosis.