非小细胞肺癌组织FIGNL1、UCHL3表达与同源重组修复基因的相关性及其临床预后意义OA
The FIGNL1,UCHL3 expression in non-small cell lung cancer tissues and correlation with homologous recombination repair genes and clinical prognostic significance
目的 研究非小细胞肺癌(NSCLC)组织中Fidgetin样因子1(FIGNL1)、泛素羧基末端水解酶L3(UCHL3)的表达,分析两者与同源重组修复基因人乳腺癌易感基因1(BRCA1)、切除修复交叉互补基因1(ERCC1)mRNA的相关性及预后意义.方法 选取2018年6月—2021年6月南京医科大学附属南京医院/南京市第一医院心胸外科收治的NSCLC患者148例的手术样本.采用免疫组化检测FIGNL1、UCHL3蛋白表达,qPCR检测癌旁组织与癌组织中FIGNL1、UCHL3 mRNA及同源重组修复相关基因BRCA1、ERCC1 mRNA表达;应用癌症基因组图谱(TCGA)数据库分析NSCLC癌组织和癌旁组织中FIGNL1、UCHL3 mRNA及BRCA1、ERCC1 mRNA表达;采用Pearson相关分析 FIGNL1、UCHL3 mRNA 表达与 BRCA1、ERCC1 mRNA 表达的相关性;Kaplan-Meier 曲线分析 FIGNL1、UCHL3 蛋白表达对NSCLC患者生存预后的影响;Cox回归分析NSCLC患者预后的影响因素.结果 TCGA数据库分析显示,NSCLC 癌组织 FIGNL1、UCHL3、BRCA1、ERCC1 表达均高于癌旁组织(t/P=11.630/<0.001、18.582/<0.001、10.721/<0.001、6.716/<0.001);qPCR 检测结果显示,NSCLC 癌组织 FIGNL1、UCHL3、BRCA1、ERCC1 表达均高于癌旁组织(t/P=44.234/<0.001、36.435/<0.001、49.040/<0.001、38.602/<0.001);TCGA 数据分析结果显示,NSCLC 癌组织中 FIGNL1 mRNA、UCHL3 mRNA 与 BRCA1 mRNA、ERCC1 mRNA 表达均呈正相关(FIGNL1:r/P=0.724/<0.001、0.637/<0.001;UCHL3:r/P=0.506/<0.001、0.550/<0.001);Pearson 相关分析证实,NSCLC 癌组织中 FIGNL1 mRNA、UCHL3 mRNA 与BRCA1 mRNA、ERCC1 mRNA 表达均呈正相关(FIGNL1:r/P=0.661/<0.001、0.589/<0.001,UCHL3:r/P=0.710/<0.001、0.632/<0.001);NSCLC 癌组织中 FIGNL1、UCHL3 阳性率高于癌旁组织(x2/P=120.311/<0.001、115.558/<0.001);淋巴结转移、TNM分期ⅢA期的NSCLC患者癌组织中FIGNL1、UCHL3阳性率高于无淋巴结转移、TNM分期Ⅰ~Ⅱ 期的患者(FIGNL1:x2/P=7.801/0.005、19.592/<0.001;UCHL3:x2/P=6.891/<0.009、14.520/<0.001);FIGNL1、UCHL3阳性组3年平均生存时间低于阴性组(Log-Rank x2/P=13.627/<0.001、11.342/<0.001);淋巴结转移、TNM分期ⅢA期、FIGNL1阳性、UCHL3阳性是NSCLC患者预后不良的独立危险因素[HR(95%CI)=1.298(1.082~1.559),1.330(1.080~1.637),1.189(1.020~1.385),1.240(1.001~1.535)].结论 FIGNL1、UCHL3 在 NSCLC 癌组织中表达上调,且与同源重组修复基因表达水平呈正相关,可能成为评估NSCLC患者预后的新型分子标志物.
Objective To investigate the expression of fidgetin like factor 1(FIGNL1)and ubiquitin carboxy-termi-nal hydrolase L3(UCHL3)in non-small cell lung cancer(NSCLC)tissues,and to analyze their correlation with homologous recombination repair genes and prognostic significance.Methods A total of 148 NSCLC patients from the Department of Cardiothoracic Surgery,Nanjing Hospital Affiliated to Nanjing Medical University(Nanjing First Hospital)were collected from June 2018 to June 2021.TCGA database data and qPCR experiments were used to detect the expression of FIGNL1 mRNA,UCHL3 mRNA,breast cancer susceptibility gene 1(BRCA1)mRNA,and excision repair cross-complementing gene 1(ERCC1)mRNA.Pearson correlation analysis was used for correlation assessment.FIGNL1 and UCHL3 proteins were detec-ted by immunohistochemistry.Kaplan-Meier curves and multivariate Cox regression analysis were used to investigate the im-pact of FIGNL1 and UCHL3 protein expression on prognosis.Results TCGA database and qPCR experiments showed that the expression levels of FIGNL1 mRNA,UCHL3 mRNA,BRCA1 mRNA,and ERCC1 mRNA in cancer tissues were signifi-cantly higher than those in adjacent normal tissues(t/P=11.630/<0.001,18.582/<0.001,10.721/<0.001,6.716/<0.001;44.234/<0.001,36.435/<0.001,49.040/<0.001,38.602/<0.001).The expression levels of FIGNL1 mRNA,UCHL3 mRNA,BRCA1 mRNA,and ERCC1 mRNA in NSCLC tissues were positively correlated with each other(r=0.661,0.589;0.710,0.632,all P<0.001).The positive rates of FIGNL1 and UCHL3 in NSCLC cancer tissues were 72.97%(108/148)and 68.92%(102/148),respectively,which were significantly higher than those in adjacent normal tissues(9.46%[15/148]and 8.11%[12/148])(x2=120.31,115.56,both P<0.001).The positive rates of FIGNL1 and UCHL3 in cancer tissues were significantly higher in patients with TNM stage Ⅲ A and lymph node metastasis than in those with stage Ⅰ-Ⅱ and without lymph node metastasis(x2/P=19.592/<0.001,7.801/0.005,14.520/<0.001,6.891/0.009).The mean 3-year survival time of the FIGNL1-positive group was(28.97±0.95)months,which was significantly lower than that of the negative group(34.11±0.75)months(Log-rank x2=13.627,P<0.001).The mean 3-year survival time of the UCHL3-positive group was(28.72±0.96)months,which was significantly lower than that of the negative group(34.67±0.51)months(Log-rank x2=11.342,P<0.001).FIGNL1 positivity,UCHL3 positivity,TNM stage Ⅲ A,and lymph node metastasis were independent risk factors affecting the prognosis of NSCLC patients[HR(95%CI)=1.330(1.080-1.637),1.298(1.082-1.559),1.189(1.020-1.385),1.240(1.001-1.535)].Con-clusion The upregulation of FIGNL1 and UCHL3 expression in NSCLC is associated with the expression of homologous re-combination repair genes.These proteins may serve as novel tumor markers for prognostic evaluation of NSCLC.
李良鹏;杨小兵;时俊峰;郑琳;马志飞
210006 南京,南京医科大学附属南京医院/南京市第一医院心胸外科210006 南京,南京医科大学附属南京医院/南京市第一医院病理科210006 南京,南京医科大学附属南京医院/南京市第一医院肿瘤科210006 南京,南京医科大学附属南京医院/南京市第一医院心胸外科210006 南京,南京医科大学附属南京医院/南京市第一医院心胸外科
医药卫生
非小细胞肺癌Fidgetin样因子1泛素羧基末端水解酶L3同源重组修复基因预后
Non-small cell lung cancerFidgetin like factor 1Ubiquitin carboxy-terminal hydrolase L3Homologous recombination repair genePrognosis
《疑难病杂志》 2026 (5)
513-518,6
江苏省医院管理创新研究课题(JSYGY-3-2025-545) Jiangsu Hospital Management Innovation Research Project(JSYGY-3-2025-545)
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