Prognostic Value And Immune Function Analysis Of M6a-related LncRNA In Cervical Carcinoma

Background: Cervical cancer is the fourth common cancer among women in terms of morbidity and mortality.The imbalance between Human Development Index（HDI）and poverty rate has caused economic and geographical disparities in the mortality and incidence of cervical cancer in the world,with cervical cancer mortality rates in high-income countries only 1/18 of those in low-income countries.In addition to persistent infection with High-Risk Human Papilloma Virus（HR-HPV）,HIV and Chlamydia trachomatis infection,smoking,too many deliveries and long-term use of oral contraceptives are also is main known risk factors.Cervical cancer is prone to recurrence and metastasis,and has worse clinical prognosis.15-61% Patients who belongs to International Federation of Gynecology and Obstetrics（FIGO）stages I-III have metastases within two years after treatment,with 5-year survival rates as low as17%.Some research suggest that immunotherapy offers new cure hope,but the limitations are that there are some individual differences in how individuals respond to different treatment plans.Therefore,finding more valuable biomarkers to evaluate prognosis and predict immunotherapy response is important.N6-methyladenosine（m6A）modification is the most abundant RNA post-transcriptional modification in eukaryotes.Abnormal changes in m6A-modification may affect the development of cancer,patient response to immunotherapy and clinical prediction of prognosis.Abnormal expression of long non-coding RNA（lncRNA）is also common in cervical cancer and lncRNA play an important role in transcription and posttranscriptional modifications by regulating gene expression.,also m6A-associated lncRNA plays an important role in the prognostic value of other cancers and in predicting immunotherapy response.The role of m6A-related lncRNA in cervical cancer remains to be explored.Understanding the expression patterns of lncRNA and m6 A modifications in cervical cancer may help identify prognostic biomarkers.Methods: In this study,we obtained transcriptome and clinical data of Cervical squamous cell carcinoma and endocervical adenocarcinoma（CESC）from The Cancer Genome Atlas（TCGA）database（https://www.cancer.gov/）,and m6A-related lncRNAs were screened by co-expression analysis.Six m6A-related lncRNAs were finally identified by performing univariate Cox regression analysis,least absolute shrinkage and selection operator（LASSO）and multivariate Cox regression analysis to construct a prognostic risk assessment model,and the risk scores of the patients in the training cohort were calculated.Based on the median of risk scores,we divided the training cohort patients into low-risk group and high-risk group.Kaplan-Meier survival analysis（K-M analysis）,principal component analysis（PCA）,GO functional analysis and column line plots were used to analyze the accuracy of the risk model.Univariate and multivariate Cox regression analyses were performed to verify the independence of the risk model.The efficacy of Immune checkpoint suppression therapy in patients was predicted by using this model to regroup patients and examine each group’s tumor mutational burden（TMB）and tumor immune dysfunction and exclusion（TIDE）prediction scores.Drug sensitivity prediction was also performed for this model.Then the expression levels of m6A-related lncRNAs were validated by collecting cervical cancer clinical specimens,and the lncRNA PCBP1-AS1 with the most significant expression differences was selected to explore its possible mechanism of action in cervical cancer.Conclusion: Bioinformatics analysis demonstrated that the prognostic risk assessment model based on 6 m6A-related lncRNAs was an independent predictor of cervical cancer prognosis.According to the risk assessment model,5 potential therapeutic agents for cervical cancer patients were screened,and may have guiding value for clinical medication.Based on the statistical results of TMB and TIDE scores,our risk model was not sensitive and specific in predicting response to immunotherapy,but it still showed differences between two groups,and can provide some reference for individualized immunotherapy.Clinical specimens validated that the expression levels of m6A-related lncRNAs we screened were the same as those in the biogenesis analysis,and knocking down PCBP1-AS1 may promote cervical cancer metastasis by promoting EMT progression.This prognostic risk assessment model based on m6A-related lncRNAs may be expected to predict the prognosis of patients with cervical cancer and provide reference for making immunotherapy plans.