Screening and validation of chemoresistance marker in lung adenocarcinoma based on gene expression profile

Acta Universitatis Medicinalis Anhui     font:big middle small

Found programs: Joint Special Project for Regional High-Incidence Diseases Research , Natural Science Founda- tion of Guangxi ( No . 2023GXNSFAA026338) ; National Natural Science Foundation of China ( Nos . 81803564 , 82160448 , 82160482 ) ; National College Student Innovation and Entrepreneurship Training Project (Nos . 202210598040 , 202210598038 , 202210598033 , 202110598029)

Authors:Wei Handong1 , Chen Shuxing2 , Liu Linting2 , Jing Zihan3 , Yang Yiting1 , Song Qiong1 , Wang Wenchu1 , Zou Chunlin1 , Wang Lihui 1

Keywords:non small cell lung cancer; lung adenocarcinoma; bioinformatics analysis; differentially expressed genes; molecular markers; chemoresistance

DOI:10.19405/j.cnki.issn1000-1492.2025.10.006

〔Abstract〕 To discover molecular markers associated with lung adenocarcinoma diagnosis/prognosis and drug resistance through screening of differentially expressed genes based on published chip data in gene expression databases using bioinformatics methods . Methods Comprehensive analysis was performed in available mRNA mi- croarray datasets including lung adenocarcinoma tissues dataset GSE32863 and lung adenocarcinoma taxane-platin resistance dataset GSE77209 from the gene expression omnibus (GEO) database . Gene ontology enrichment analy- sis , gene pathway enrichment analysis and protein interaction network analysis were performed based on significant- ly correlated genes . The expression level of genes was validated in the cancer genome atlas (TCGA) dataset. Sur- vival differences were assessed by the log-rank test in TCGA lung adenocarcinoma dataset. Based on the publica- tions genomics of drug sensitivity in cancer (GDSC) database in CellMiner cross database (CellMiner CDB) , Pear- son correlation analysis was used to analyze the correlation between differentially expressed genes and the half-maxi- mal inhibitory concentration (IC50 ) of anticancer drugs . Results There were a total of 77 genes which had a dif- ferent expression in resistance lung adenocarcinoma cells and lung adenocarcinoma cancer tissues . The functional enrichment analysis showed that these co-different expression genes were mainly enriched in microtubule , extracel- lular exosome , cell cycle and signaling by nuclear receptors . Protein-protein interactions (PPI) network screened 6 most connected genes as molecular complex (MCODE) . Among the MCODE , overexpressed ubiquitin conjugating enzyme E2 T (UBE2T) , kinesin family member 20A(KIF20A) , PCNA clamp associated factor (KIAA0101) , pi- tuitary tumor-transforming gene 1 ( PTTG1) and NIMA related kinase 2 ( NEK2) were associated with poor out- comes . Survival analysis results showed that these five genes were upregulated in lung adenocarcinoma tissues and drug-resistant cells and were significantly associated with poor prognosis in lung adenocarcinoma patients . Drug sen- sitivity analysis results suggested that high expression of PTTG1 and UBE2T was significantly associated with sensi-tivity to multiple anticancer drugs , including paclitaxel and docetaxel . RT-PCR validation showed that PTTG1 and UBE2T were highly expressed in docetaxel-resistant cells A549-TXR and H358-TXR. Conclusion PTTG1 and UBE2T holds the potential to be chemoresistance markers in lung adenocarcinoma.