KIAA0101 And ARHGAP30 Moleculesaffect Lung Adenocarcinoma Patient Prognosis By Regulating Tumorimmune Infiltration

Introduction: Lung cancer is the malignant tumor with the largest number of new cases and deaths in China,and the pathological type of lung cancer is dominated by lung adenocarcinoma.Lung cancer includes multiple subtypes,and the proportion of lung adenocarcinoma has increased in recent years.Despite significant advances in chemotherapy and molecularly targeted therapy for lung adenocarcinoma,the survival rate of lung adenocarcinoma remains unsatisfactory.To improve the prognosis of patients with lung adenocarcinoma,more lung adenocarcinoma targeting molecules should be identified to diagnose,treat,and judge the prognosis of patients.Bioinformatics has taken an important position in medical research and has generated a lot of scientific research results.We applied bioinformatics to the study of discovering new targeting molecules for lung adenocarcinoma.Proliferating cell nuclear antigen binding factor(KIAA0101 / PCLAF)regulates cellular DNA synthesis and cell cycle progression,and whether KIAA0101 m RNA levels in lung adenocarcinoma are associated with prognosis and tumor immune infiltration is currently unknown.Rho GTPase activating protein 30(ARHGAP30)can enhance the intrinsic hydrolysis of GTP and negatively regulate Rho GTPases.The relationship between the expression of arhgap30 and lung adenocarcinoma is also unclear.This study intends to use bioinformatics methods to deeply investigate the relationship between KIAA0101 and ARHGAP30 and lung adenocarcinoma,to lay the foundation for the discovery of new targeted therapeutic molecules and immunotherapy for lung adenocarcinoma,this study is intended to be divided into two parts,KIAA0101 and ARHGAP30,to be analyzed and elaborated.Part Ⅰ Expression,prognosis,tumor immunity,gene set enrichment analysis and drug transcriptomic analysis of KIAA0101 and lung adenocarcinoma MethodsMethods: differential expression analysis of KIAA0101 was performed using datasets of 8 pairs of lung adenocarcinoma tissues and normal lung tissues from Oncomine database,GEPIA database and Ualcan database.The prognosis of patients with different KIAA0101 expression levels was assessed using 6 pairs of lung adenocarcinoma datasets with different KIAA0101 expression levels from the Prognostan database,GEPIA and other databases.Tumour immune infiltration associated with KIAA0101 was analysed using TISIDB.Gene set enrichment analysis of KIAA0101 was performed using the Linkedmics database.Pharmacotranscriptomic analysis of KIAA0101 was performed using the Drugbank database.Results: the expression of KIAA0101 in lung adenocarcinoma tissues was higher than that in normal lung tissues(8 pairs of datasets,statistical significance).Lung adenocarcinoma patients with low expression of KIAA0101 had a better prognosis than those with high expression(6 pairs of datasets,statistical significance).We discovered a gene regulatory network of KIAA0101 in lung adenocarcinoma.Also found a correlation between KIAA0101 expression and different tumor infiltrating lymphocytes(TILs),immunosuppressive agents,immunostimulatory agents,MHC molecules,chemokines and receptors,and found that we found that the metabolism of seven drugs or compounds upregulated KIAA0101 expression,and also found that the metabolism of 24 drugs downregulated KIAA0101 expression.Conclusions: KIAA0101 was differentially expressed in lung adenocarcinoma tissues,and lung adenocarcinoma patients with high KIAA0101 expression had a poor prognosis.KIAA0101 has been implicated in cell cycle,ribosome,splicing,and DNA replication.It may provide a new direction for the diagnosis,prognosis evaluation,immunotherapy and targeted therapy of lung adenocarcinoma.Part Ⅱ Expression,prognosis,DNA methylation,tumor immunity, and gene set enrichment analysis of ARHGAP30 and lung adenocarcinomaMethods: differential analysis of ARHGAP30 m RNA and protein was performed using Oncomine database,Sur Express database,GEPIA database,and Ualcan database(6 datasets).Twelve datasets from multiple databases such as prognoscan were utilized to evaluate the prognosis of patients with different ARHGAP30 expression levels.Gene set enrichment analysis,including analysis of KEGG pathways,Panther pathways,Reactome pathways,Wiki pathways,Gene ontology,Kinome target networks,Transcription factor networks,and protein-protein interaction networks,was performed on ARHGAP30 using the Linkedomics database.Correlation analysis between arhgap30 expression and tumor infiltrating lymphocytes,immunostimulators,major histocompatibility complex molecules,chemokines,and chemokine receptors in lung adenocarcinoma tissues was performed using the TISIDB database.Results: DNA methylation of ARHGAP30 was negatively correlated with ARHGAP30 expression(6 pairs of datasets,statistically significant).Lung adenocarcinoma patients with higher DNA methylation of ARHGAP30 had a worse prognosis.Lung adenocarcinoma patients with low ARHGAP30 expression had a worse prognosis than those with high ARHGAP30 expression(12 pairs of datasets,statistical significance).ARHGAP30 expression in lung adenocarcinoma is positively correlated with the levels of tumor infiltrating lymphocytes,whereas methylation of ARHGAP30 is negatively correlated with the levels of tumor infiltrating lymphocytes.The top five pathways are cell cycle,ribosome,proteasome(supplementary Fig.4),spliceosome and DNA replication.Gene Ontology(go)results for gene sets(cellular components)include condensed chromosomes,chromosome territories,mitochondrial protein complexes,ribosomes,and the spindle.Gene Ontology(go)outcomes for gene sets(biological processes)included chromosome segregation,DNA replication,cell cycle checkpoints,double strand break repair,and spindle organization.Gene Ontology(go)outcomes of the genome(molecular function)include structural composition of the ribosome,catalytic activity,DNA action,single stranded DNA binding,helicase activity and catalytic activity and acting on RNA.Conclusions: ARHGAP30 is differentially expressed in lung adenocarcinoma tissues,and DNA methylation of ARHGAP30 is associated with poor prognosis in lung adenocarcinoma patients and promotes lung adenocarcinoma formation and growth by inhibiting multiple pathways of tumor infiltrating immunity,which provides a new idea for regulating gene therapy in lung adenocarcinoma.Bioinformatics research is important in the mining of new biomarkers for lung adenocarcinoma and may expand new directions for lung adenocarcinoma research with high efficiency.