Study On Expression Of M~6A Demethylase ALKBH5 In Papillary Thyroid Carcinoma And Its Clinical Significance

Objective:In this paper,the expression of Alk B Homolog 5(Alk B Homolog 5,ALKBH5)in thyroid cancer and its correlation with clinical parameters were preliminically discussed in bioinformatics database,and the biological processes and signaling pathways in which ALKBH5 might be involved were analyzed.In addition,immunohistochemical experiment was used to detect the expression of ALKBH5 in thyroid papillary carcinoma and analyze its clinical significance.It provides clues for ALKBH5 to be a new biomarker to predict the progression and prognosis of papillary thyroid carcinoma and its targeted therapy.Methods:1.Based on the data of thyroid cancer cases in The Cancer Genome Atlas(TCGA)database,the difference of ALKBH5 expression in thyroid cancer and normal thyroid tissues was explored,and the relationship between ALKBH5 and different clinical factors was further analyzed.Kaplan-Meier survival analysis was used to explore whether the expression level of ALKBH5 in thyroid cancer tissues was related to the relapse-free survival of patients.2.Functional enrichment analysis based on Gene Ontology(GO)and Kyoto Encyclopedia of Genesand Genomes(KEGG)pathway enrichment analysis,genomes The biological processes and pathways that ALKBH5 may participate in in thyroid cancer were investigated.3.The postoperative specimens of patients diagnosed with papillary carcinoma of thyroid were collected from the Department of Pathology,Affiliated Hospital of Guilin Medical College and made into paraffin sections.The corresponding normal thyroid tissues more than 2cm away from the tumor margin were used as the control group for immunohistochemical experiments.Chi-square test was used to analyze the difference of expression of m~6A demethylase ALKBH5 in papillary thyroid carcinoma and normal thyroid tissue,and the relationship between ALKBH5 and related clinical factors.Results:The results of TCGA database analysis showed that ALKBH5expression in thyroid cancer was lower than that in normal thyroid tissue(P<0.001).The expression of ALKBH5 in thyroid carcinoma was correlated with clinical stage and pathological classification(P<0.001).The expression of ALKBH5 in thyroid carcinoma was correlated with lymph node metastasis(P<0.001).There was no significant difference in ALKBH5 expression among different race,sex and age groups in thyroid cancer patients(P>0.05).ALKBH5 expression level was correlated with recurrent-free survival of thyroid cancer patients(P<0.001).GO functional enrichment showed that ALKBH5may be involved in biological processes including protein ubiquitination,intracellular protein transport,DNA transcription regulation,ubiquitin-dependent protein catabolism,and endoplasmic reticulum to Golgi vesicle-mediated transport in thyroid cancer.KEGG pathway enrichment analysis showed that ALKBH5 may be involved in endoplasmic reticulum protein processing,autophagy signaling pathway and insulin signaling pathway in thyroid cancer.Immunohistochemical results showed that ALKBH5expression in papillary thyroid carcinoma was lower than that in normal thyroid tissue(P<0.01).ALKBH5 expression in thyroid papillary carcinoma was correlated with lymph node metastasis(P<0.05),but had no significant correlation with patient age,sex and tumor size(P>0.05).Conclusions:The expression of m~6A demethylase ALKBH5 in thyroid papillary carcinoma was lower than that in normal thyroid tissue,and the expression level was negatively correlated with lymph node metastasis,but not significantly correlated with age,gender and tumor size,suggesting that Alk BH5may be involved in the occurrence and development of thyroid papillary carcinoma.