中国肺癌杂志2023，Vol.26Issue(12)：889-900,12.DOI:10.3779/j.issn.1009-3419.2023.106.23
"磨玻璃影"特征的早期肺腺癌中MPP成分的突变特征分析及ZNF469基因的探索
Mutational Signatures Analysis of Micropapillary Components and Exploration of ZNF469 Gene in Early-stage Lung Adenocarcinoma with Ground-glass Opacities
摘要
Abstract
Background and objective In China,lung cancer remains the cancer with the highest incidence and mortality rate.Among early-stage lung adenocarcinomas(LUAD),the micropapillary(MPP)component is prevalent and typi-cally exhibits high aggressiveness,significantly correlating with early metastasis,lymphatic infiltration,and reduced five-year survival rates.Therefore,the study is to explore the similarities and differences between MPP and non-micropapillary(non-MPP)components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD,identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene,a member of the zinc-finger protein family,and the prognosis of early-stage LUAD,as well as its correlation with immune infiltration.Methods A total of 31 malig-nant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdis-section.Whole-exome sequencing(WES)was performed on the components of early-stage malignant pulmonary nodules.Mu-tational signatures analysis was conducted using R packages such as maftools,Nonnegative Matrix Factorization(NMF),and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues.Furthermore,we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas(TCGA)database to investigate its potential association with the prognosis.We also investigated gene interaction networks and signal-ing pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Lastly,we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases.Results MPP components exhibited a higher number of genomic variations,particularly the 13th COSMIC(Catalogue of Somatic Mutations in Can-cer)mutational signature characterized by the activity of the cytidine deaminase APOBEC family,which was unique to MPP components compared to non-MPP components in tumor tissues.This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD.Additionally,MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden(TMB),indicating that these patients may be more likely to benefit from immuno-therapy.The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue,and was associated with poor prognosis in LUAD patients(P<0.05).Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1,COL1A1,COL1A2,TGFB2,MMP2,COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix.ZNF469 expression was positively correlated with immune cell infiltration in LUAD(P<0.05).Conclusion The study has unveiled distinctive mutational signa-tures in the MPP components of early-stage invasive LUAD in the Asian population.Furthermore,we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD,suggesting its potential as a diagnostic and prognostic biomarker in LUAD.关键词
肺肿瘤/磨玻璃影/微乳头成分/突变特征分析/ZNF469基因Key words
Lung neoplasms/Ground-glass opacities/Micropapillary/Mutational signatures analysis/ZNF469 gene引用本文复制引用
许有涛,吴金涛,陈鹏,袁方慰,余新宇,季金芾,李知桐,朱鹏程,孙宇翔,刘桐言,尹荣,孙钦泓,许林,王思炜,朱鸿宇,董国璋,孟凡尘,夏志军,游静,孔祥茹.."磨玻璃影"特征的早期肺腺癌中MPP成分的突变特征分析及ZNF469基因的探索[J].中国肺癌杂志,2023,26(12):889-900,12.基金项目
本研究受国家自然科学基金项目(No.82203202)资助 This study was supported by the grant from National Natural Science Foundation of China(No.82203202)(to Siwei WANG). （No.82203202）
