NFE2L3在直肠癌中的表达及预后意义
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摘要
目的探索转录因子(NF-E2)相关因子3(NFE2L3)在直肠癌(RC)患者中的表达水平及其与临床预后指标的相关性。方法应用癌症相关数据库GEPIA和Oncomine中NFE2L3基因的表达水平和预后行生物信息预测;回顾性分析66对RC与配对癌旁组织,行免疫组化的方法检测NFE2L3基因蛋白表达;而后通过Kaplan-Meier单因素和Cox多因素分析研究NFE2L3表达水平与RC患者预后的关系。结果 GEPIA和Oncomine数据库均预测到NFE2L3基因mRNA水平在RC组织中显著高于正常组织(P<0.05),GEPIA数据库显示NFE2L3基因高表达的RC患者临床预后优于低表达者(P=0.041),且该结果与免疫组化结果相一致,RC组织中NFE2L3蛋白高表达(P<0.001),且临床预后优于低表达者(P=0.009)。多因素及单因素生存分析结果提示:NFE2L3蛋白表达水平是RC患者预后的独立预测因子。结论 NFE2L3基因在RC中高表达,可以作为预测RC患者预后良好的独立预测因子,有望成为未来RC患者治疗的新靶点。
Objective To explore the expression of NFE2 L3 and its prognostic significance in patients with rectal cancer(RC). Methods Using the data of the cancer database gene expression profiling interactive analysis(GEPIA) and Oncomine,the expression levels and prognosis of genes NFE2 L3 were used for bioinformatics prediction. 66 cases of RC patients tissue samples and paired normal tissues were collected retrospectively to examine the NFE2 L3 protein expression level by immunohistochemical staining. The relationship between NFE2 L3 expression level and prognosis of rectal cancer patients was analyzed by Kaplan-Meier univariate and Cox multivariate factors. Results Both GEPIA and Oncomine databases predicted that NFE2 L3 mRNA levels in rectal cancer tissues were significantly higher than those in normal tissues(P<0.05). GEPIA data showed that patients with high NFE2 L3 mRNA levels had significantly better prognosis than patients with low expression(P=0.041). Subsequent immunohistochemical results confirmed the above prediction results. NFE2 L3 protein levels in RC were highly expressed(P<0.001) compared with those in normal tissues, and the prognosis was better than that of patients with low expression of NFE2 L3(P=0.009). Multivariate and univariate survival analyses revealed that NFE2 L3 high expression could be used as an independent predictor of good prognosis in RC patients.Conclusion NFE2 L3 gene is highly expressed in rectal cancer, and highly expressed NFE2 L3 can be used as an independent predictor of good prognosis in rectal cancer patients. NFE2 L3 gene is expected to be a new target for the treatment of patients with rectal cancer in the future.
Objective To explore the expression of NFE2 L3 and its prognostic significance in patients with rectal cancer(RC). Methods Using the data of the cancer database gene expression profiling interactive analysis(GEPIA) and Oncomine,the expression levels and prognosis of genes NFE2 L3 were used for bioinformatics prediction. 66 cases of RC patients tissue samples and paired normal tissues were collected retrospectively to examine the NFE2 L3 protein expression level by immunohistochemical staining. The relationship between NFE2 L3 expression level and prognosis of rectal cancer patients was analyzed by Kaplan-Meier univariate and Cox multivariate factors. Results Both GEPIA and Oncomine databases predicted that NFE2 L3 mRNA levels in rectal cancer tissues were significantly higher than those in normal tissues(P<0.05). GEPIA data showed that patients with high NFE2 L3 mRNA levels had significantly better prognosis than patients with low expression(P=0.041). Subsequent immunohistochemical results confirmed the above prediction results. NFE2 L3 protein levels in RC were highly expressed(P<0.001) compared with those in normal tissues, and the prognosis was better than that of patients with low expression of NFE2 L3(P=0.009). Multivariate and univariate survival analyses revealed that NFE2 L3 high expression could be used as an independent predictor of good prognosis in RC patients.Conclusion NFE2 L3 gene is highly expressed in rectal cancer, and highly expressed NFE2 L3 can be used as an independent predictor of good prognosis in rectal cancer patients. NFE2 L3 gene is expected to be a new target for the treatment of patients with rectal cancer in the future.
引文
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[2] Blank V,Andrews N C.The Maf transcription factors:regulators of differentiation[J].Trends Biochem Sci,1997,22(11):437-41.
[3] Willenbrock K,Küppers R,Renné C,et al.Common features and differences in the transcriptome of large cell anaplastic lymphoma and classical Hodgkin's lymphoma[J].Haematologica,2006,91(5):596-604.
[4] Rhee D K,Park S H,Jang Y K.Molecular signatures associated with transformation and progression to breast cancer in the isogenic MCF10 model[J].Genomics,2008,92(6):419-28.
[5] 陈恩碧,邹继彬,黄勇波,等.CTHRC1和NFE2L3在结直肠癌组织中的表达及相关性[J].中国当代医药,2012,19(16):8-9.
[6] Tang Z,Li C,Kang B,et al.GEPIA:a web server for cancer and normal gene expression profiling and interactive analyses[J].Nucleic Acids Res,2017,45(W1):W98-102.
[7] Rhodes D R,Kalyana-Sundaram S,Mahavisno V,et al.Oncomine 3.0:genes,pathways,and networks in a collection of 18,000 cancer gene expression profiles[J].Neoplasia,2007,9(2):166-80.
[8] Wang W,Zhang M,Peng Y,et al.Ubiquitin associated protein 2-like (UBAP2L) overexpression in patients with hepatocellular carcinoma and its clinical significance[J].Med Sci Monit,2017,23:4779-88.
[9] Almstrup K,Ottesen A M,Sonne S B,et al.Genomic and gene expression signature of the pre-invasive testicular carcinoma in situ[J].Cell Tissue Res,2005,322(1):159-65.
[10] Wang H,Zhan M,Yang R,et al.Elevated expression of NFE2L3 predicts the poor prognosis of pancreatic cancer patients[J].Cell Cycle,2018,17(17):2164-74.
[11] Chevillard G,Paquet M,Blank V.Nfe2l3 (Nrf3) deficiency predisposes mice to T-cell lymphoblastic lymphoma[J].Blood,2011,117(6):2005-8.
[12] 许红民,王强,白雪娟,等.利用全基因组寡核苷酸筛选大肠癌差异表达基因[J].第一军医大学学报,2005,25(9):1109-13.
[13] 王强,李晓利,白雪娟,等.Nrf3基因对大肠癌LoVo细胞系生长的影响[J].军医进修学院学报,2008,29(4):262-4.
[14] 李晓利,王强,白雪娟,等.Nrf3基因对肝癌SMMC7721细胞系的体外研究[J].军医进修学院学报,2010,31(9):924-6.
[15] Chowdhury A M M A,Katoh H,Hatanaka A,et al.Multiple regulatory mechanisms of the biological function of NRF3 (NFE2L3) control cancer cell proliferation[J].Sci Rep,2017,7(1):12494.