医学分子生物学杂志 ›› 2024, Vol. 21 ›› Issue (5): 452-457.doi: 10.3870/j.issn.1672-8009.2024.05.010

• 论著 • 上一篇    下一篇

非小细胞肺癌中 FtMt 蛋白的表达水平及其临床病理意义 #br#

  

  1. 南通市第二人民医院检验科 江苏省南通市, 226000
  • 出版日期:2024-09-30 发布日期:2024-10-25
  • 基金资助:
    2023 年度南通市卫生健康委员会青年科研课题 (No. QNZ2023060)

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

  1. Department of Laboratory, the Second Peoples Hospital of Nantong, Nantong, Jiangsu, 22600, China
  • Online:2024-09-30 Published:2024-10-25

摘要: 目的 研究非小细胞肺癌 ( non-small cell lung cancer, NSCLC) 中线粒体铁蛋白 ( mitochondrialferritin, FtMt) 表达与临床病理和分子特征的相关性 方法 选择 2018 9 ~ 2020 12 月期间经病理确诊为 NSCLC 的手术切除标本 154 , 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 EGFRALKKRAS 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) 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、 pTNM Ⅲ 有淋巴结转移的 NSCLC 组织中 FtMt 阳性表达率高于高分化、 pTNM Ⅰ ~ Ⅱ 无淋巴结转移的 NSCLC ( P< 0. 05); 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 mRNA 表达水平及 EGFR 突变率升高, E-cadherin、 Bax、 Caspase-3 mRNA 表达水平及无瘤生存率总生存率均降低 (P< 0. 05)。 结论 NSCLC 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

关键词: 非小细胞肺癌, 线粒体铁蛋白, 铁死亡, 凋亡, 上皮间质转化

Abstract: Objective To study the relationships between the expression level of mitochondrialferritin (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 NSCLCfrom 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 tumorfree survival and overall survival. Results The positive expression rate of FtMt in the NSCLC tissueswas higher than that in the adjacent tissues ( P < 0. 05). The positive expression rates of FtMt inNSCLC tissues with low differentiation, pTNM stage Ⅲ , and lymph node metastasis were higherthan those with high differentiation, pTNM stage Ⅰ -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 themRNA 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 withnegative FtMt expressions (P < 0. 05). Conclusion The positive expression of FtMt in NSCLC isassociated with pathological progression, EGFR mutation, and reduced survival. The biologicalmechanisms may associate with abnormal epithelial mesenchymal transformation, ferroptosis and mitochondrial pathway apoptosis.

Key words:

non-small cell lung cancer, mitochondrial ferritin, ferroptosis, apoptosis, epithelial-mesenchymal transformation

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