Screening and immune correlation analysis on differential genes for radiosensitivity of cervical cancer

HU Yu; WANG Hanmeng; CHEN Ranzhong; PENG Changmin; LI Le; TANG Shuangyang

doi:10.3969/j.issn.1002-266X.2023.29.005

Abstract：Objective To screen the differentially expressed genes(DEGs)affecting radiosensitivity of cervical can-cer and to conduct the expression validation and immune correlation analysis by bioinformatics methods.Methods The datasets of cervical cancer tissues before or after radiotherapy,normal cervical tissues and cervical cancer tissues were downloaded from Gene Expression Database(GEO),and the DEGs of cervical cancer were screened by Rstudio software,and Venn diagram was used to screen DEGs for radiosensitivity of cervical cancer.The expression data of cervical cancer tissue samples and normal cervical tissue samples,and clinical information and follow-up data of the patients were collect-ed from TCGA database and GTEx database.DEGs for radiosensitivity of cervical cancer were screened and their expres-sion levels were analyzed from GEPIA2 database,and then the reliability of selected DEGs were verified.The key DEGs for radiosensitivity of cervical cancer were screened through the effects of different gene expression levels on patients'prog-nosis by survival analyses from GEPIA2 database.The clinical data and prognosis of patients were porformed by single fac-tor and multi-factor COX regression analyses to verify the screened key DEGs as the influencing factors on the prognosis of cervical cancer patients by Rstudio software.The protein expression of screened key DEGs between cervical cancer and normal cervical tissues was compared through HPA database.The gene enrichment analysis was set for GO function and KEGG signaling pathways of key DEGs.The relationship between the expression of key DEGs in cervical cancer and the in-filtration level of immune cells was analyzed through TIMER database.The expression of immune checkpoint-related genes were observed through TCGA database.Spearman correlation analysis was conducted on the key DEGs and immune check-point genes highly associated with cervical cancer.Results Ten DEGs with cervical cancer radiosensitivity were screened out,which were HELLS,TOP2A,KIF23,TAP1,WDR76,LMNB1,RFC4,TFRC,IFI44L and IFIT3.All 10 DEGs were highly expressed in the cervical cancer tissues.Survival analysis results showed that the overall survival and disease-free survival of cervical cancer patients with high TFRC expression were lower than those of patients with low TFRC expression,so TFRC was selected as the key DEG for radiosensitivity of cervical cancer.TFRC and TNM stage of cervical cancer were both the influential factors for the prognosis of cervical cancer through the single factor COX regression analy-sis,but were the independent risk factors through the multi-factor COX regression analysis.The protein expression of TFRC in cervical cancer tissues and normal cervical tissues was verified through HPA database,and the results showed that TFRC was highly expressed in cervical cancer tissue,but not detected in normal cervical tissues.GO functional analy-sis showed that TFRC was mainly involved in the biological processes including chromosome segregation,RNA localization and adaptive immune response,the cellular components containing chromosomal regions,ribosomal precursors,and im-mune synapses,and the molecular functions such as deconjugating enzyme activity,histone binding,and antigen binding,etc.KEGG signaling pathway enrichment analysis showed that TFRC was mainly associated with the signaling pathways such as RNA transporters,cell cycle,and allogeneic graft rejection response,etc.TIMER database analysis showed that TFRC expression in cervical cancer was positively correlated with cell purity and was negatively correlated with CD8+ T lymphocytes,and it could affect the infiltration degree of memory B lymphocytes,CD8+ T lymphocytes,macrophage M0 and resting mast cells.Spearman correlation analysis showed that TFRC expression was negatively correlated with most of immune checkpoint-related genes for cervical cancer.Conclusion TFRC is DEG for radiosensitivity of cervical cancer,which may be associated with adaptive immune responses and cervical cancer-related immune checkpoint,suggesting that it may play a role in the radioimmunotherapy for cervical cancer and influence its progression and prognosis.