Expression Levels Of NFE2L3 In Rectal Cancer And Its Prognostic Value

Rectal cancer(RC)is one of the most common gastrointestinal malignancies all over the world.Radical surgery is the main treatment at present,but 40%-50% patients die due to postoperative recurrence or metastasis.Finding effective biological indicators for predicting prognosis is a hot research topic in the diagnosis and treatment of rectal cancer.The transcription factor NF-E2-related factor 3(NF-E2-related factor 3,NFE2L3,also known as Nrf3)is the third family member of the NF-E2 family.The main biological role is to induce the expression of antioxidant genes.Recent studies have shown that NFE2L3 is highly expressed in various malignant tumors such as blood system and breast cancer,while it is closely related to the prognosis of patients.However,NFE2L3 expression levels in rectal cancer and its prognostic value still have not seen relevant reports.Therefore,in this study,we used bioinformatics prediction combined with immunohistochemistry to investigate the expression of NFE2L3 in rectal cancer and its correlation with clinical prognostic indicators.Aim: To explore the expression level of NFE2L3 and its prognostic significance in patients with rectal cancer.Materials and methods: The large cancer public databases GEPIA and Oncomine were used to explore the expression level of NFE2L3 gene and the prognosis of patients with rectal cancer.A retrospective study was conducted on the tumor and para-normal tissue samples of 66 colorectal cancer patients in the First Affiliated Hospital of Anhui Medical University,and the expression level of NFE2L3 gene protein was detected byimmunohistochemistry.The relationship between NFE2L3 expression level and prognosis of rectal cancer patients was analyzed by Kaplan-Meier univariate and Cox multivariate factors.Finally,TCGA cancer data were used to predict the possible regulatory mechanism of NFE2L3 in rectal cancer.Results: Both GEPIA and Oncomine databases predicted that NFE2L3 m RNA levels in rectal cancer tissues were dramatically higher than those in normal control(P <0.05).GEPIA data showed that rectal cancer patients with NFE2L3 high m RNA expression levels had remarkably better prognosis than patients with low expression(P =0.041).Subsequent immunohistochemical results confirmed the above prediction results.In rectal cancer patients with high expression of NFE2L3 protein(P <0.001)and high expression of NFE2L3,the prognosis was better than that of patients with low expression of NFE2L3(P= 0.009).In addition,TCGA data was used to analyze the co-expressed genes with NFE2L3.According to the correlation coefficient R>0.4,P<0.01 as the screening conditions,a total of 500 co-expressed genes were obtained.Then,KEGG pathway and Gene Ontology(GO)enrichment analysis found that the regulation mechanism of NFE2L3 in rectal cancer may be related to Erb B and Rap1 signaling pathways,etc.Conclusions: NFE2L3 gene is highly expressed in rectal cancer,and highly expressed NFE2L3 can be used as a favorably independent parameter for predicting the prognosis of patients with rectal cancer.To sum up,NFE2L3 gene is expected to be a new target for the treatment of patients with rectal cancer in the future.