非小细胞肺癌中PNCK、EGFR表达与EGFR基因突变状态的相关性

Relationship between the expression of PNCK, EGFR and EGFR genemutation in non-small cell lung cancer

目的 探讨非小细胞肺癌(non-small cell lung cancer, NSCLC)中PNCK、EGFR表达及与EGFR基因突变状态的相关性。方法 采用免疫组化EnVision法检测PNCK、EGFR蛋白在肺浸润性癌(256例)、肺浸润癌前病变(42例)和癌旁组织(40例)中的表达。应用NGS检测EGFR基因扩增、突变情况,分析PNCK、EGFR蛋白表达与NSCLC临床病理特征、EGFR基因扩增或突变的关系。利用GEPIA数据库分析肺腺癌、肺鳞状细胞癌中PNCK与EGFR基因表达的相关性。使用Kaplan-Meier Plotter数据库分析PNCK对肺癌患者预后的影响。结果 PNCK、EGFR在肺浸润性癌组中的表达(53.5%,137/256;47.7%,122/256)高于肺浸润癌前病变组(47.6%,20/42;31.0%,13/42)、癌旁组(22.5%,9/40;7.5%,3/40),三组间两两比较差异有统计学意义(P<0.05)。PNCK蛋白高表达与组织分化程度、TNM分期、淋巴结转移、远处转移相关(P<0.05);EGFR蛋白高表达与TNM分期、淋巴结转移、远处转移相关(P<0.05)。NSCLC组织中PNCK与EGFR蛋白表达呈负相关(r=-0.208,P<0.05)。EGFR蛋白在EGFR基因突变、扩增的NSCLC中表达高于野生型(P<0.05)。PNCK蛋白表达与EGFR基因突变和扩增均无相关性(P>0.05)。生物信息学数据库分析:肺腺癌、肺鳞状细胞癌中PNCK与EGFR基因表达均呈正相关(r=0.15,P<0.05;r=0.30,P<0.05),肺癌中PNCK高表达患者总生存率低(HR:1.28,95%CI:1.09~1.51,P=0.003 1)。结论 PNCK高表达与NSCLC发生、发展、不良预后有关,并与EGFR蛋白表达呈负相关,其有望成为肺癌EGFR突变患者的治疗靶点。

Purpose To investigate the correlation of PNCK and EGFR expression with EGFR gene mutation status in non-small cell lung cancer(NSCLC).Methods Immunohistochemical staining was used to detect the expression of PNCK and EGFR in 256 cases of invasive lung carcinoma,42 cases of invasive precancerous lesions and 40 cases of paracancerous lung tissues,EGFR gene amplification and mutation were detected by next-generation sequencing.The relationship between the expression of PNCK and EGFR protein and the clinicopathological features of NSCLC,the mutation status of EGFR gene and the correlation between them were analyzed.GEPIA database was used to analyze the correlation between PNCK and EGFR gene expression in lung adenocarcinoma and lung squamous cell carcinoma,and Kaplan-Meier Plotter database was used to analyze the effect of PNCK on the prognosis of lung cancer.Results Expression of PNCK and EGFR in lung invasive carcinoma(53.5%,137/256;47.7%,122/256)was higher than those of pre-invasive lesions(47.6%,20/42;31.0%,13/42)and paracancer tissue(22.5%,9/40;7.5%,3/40),pair-to-pair comparison among the three groups had statistical significance(P<0.05).The high expression of PNCK protein was correlated with the degree of cancer differentiation,TNM stage,lymph node metastasis and distant metastasis(P<0.05).The high expression of EGFR protein was correlated with TNM stage,lymph node metastasis and distant metastasis(P<0.05).There was a negative correlation between PNCK and EGFR protein expression in NSCLC tissues(r=-0.208,P<0.05).The expression of EGFR protein in NSCLC with EGFR gene mutation and amplification was higher than that of wild type(P<0.05).There was no correlation between PNCK protein expression and EGFR gene mutation and amplification(P>0.05).Bioinformatics database showed that PNCK and EGFR gene expression were positively correlated in lung adenocarcinoma and lung squamous cell carcinoma(r=0.15,P<0.05;r=0.30,P<0.05),PNCK high expression group had a shorter overall survival rate in lung cancer(HR:1.28,95%CI:1.09-1.51,P=0.0031).Conclusion The high expression of PNCK is associated with the occurrence,development,and poor prognosis of NSCLC,and negatively correlated with EGFR protein expression.It is expected to become a potential therapeutic target for EGFR mutations in NSCLC.