miR-4286与AEG-1在非小细胞肺癌组织中的表达及临床意义
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摘要
目的探讨miR-4286、星形胶质细胞上调基因-1 (AEG-1)在非小细胞肺癌(NSCLC)组织中的表达及与NSCLC临床病理特征的关系。方法分别采用原位杂交方法和免疫组织化学染色检测组织芯片中140例NSCLC癌组织及癌旁正常组织中miR-4286、AEG-1的表达,并分析两者表达水平与NSCLC临床病理特征的关系。结果 NSCLC癌组织中miR-4286高表达率为62.14%,高于癌旁正常组织的4.29%,差异有统计学意义(P<0.01);NSCLC癌组织中AEG-1高表达率为55.71%,高于癌旁正常组织的7.86%,差异有统计学意义(P<0.01)。miR-4286高表达与患者肿瘤直径大小、肿瘤TNM分期和淋巴结转移均有关(均P<0.05),AEG-1高表达与患者肿瘤TNM分期和淋巴结转移均有关(均P<0.05)。Spearman等级相关分析显示NSCLC癌组织中miR-4286的表达与AEG-1的表达呈正相关(r=0.223,P=0.008)。结论 NSCLC癌组织中miR-4286与AEG-1均高表达,miR-4286与AEG-1表达水平与TMN分期和淋巴结转移均有关,提示miR-4286和AEG-1可能参与NSCLC的发生、发展与转移。
Objective To investigate the expression of mi R-4286 and astrocyte elevated gene-1(AEG-1) in non-small cell lung cancer(NSCLC) and their relationships to clinicopathological features. Methods In situ hybridization and immunohistochemistry for mi R-4286 and AEG-1 were performed in 140 samples of NSCLC tumor tissues and adjacent normal lung tissues on tissue microarray sections, respectively. The correlation of mi R-4286 and AEG-1 expression with clinicopathologic parameters of NSCLC was analyzed. Results The high expression rate of mi R-4286 in tumor tissues was 62.14%, which was higher than that in adjacent normal tissues(4.29%)(P<0.01). The high expression rate of AEG-1 in tumor tissues was 55.71%, which was higher than that in adjacent normal tissues(7.86%)(P<0.01). The upregulated expression of mi R-4286 in NSCLC was correlated with tumor size, lymph node metastasis and TNM stage(all P<0.05), while the high expression of AEG-1 in NSCLC was associated with TNM stage and lymph node metastasis(both P<0.05). Moreover, Spearman analysis showed a positive correlation between mi R-4286 expression and AEG-1 expression in NSCLC(r=0.223, P=0.008). Conclusion The high expression of mi R-4286 and AEG-1 in NSCLC is correlated with TNM stage and lymph node metastasis, suggesting that both mi R-4286 and AEG-1 may be involved in the occurrence, development and metastasis of NSCLC.
Objective To investigate the expression of mi R-4286 and astrocyte elevated gene-1(AEG-1) in non-small cell lung cancer(NSCLC) and their relationships to clinicopathological features. Methods In situ hybridization and immunohistochemistry for mi R-4286 and AEG-1 were performed in 140 samples of NSCLC tumor tissues and adjacent normal lung tissues on tissue microarray sections, respectively. The correlation of mi R-4286 and AEG-1 expression with clinicopathologic parameters of NSCLC was analyzed. Results The high expression rate of mi R-4286 in tumor tissues was 62.14%, which was higher than that in adjacent normal tissues(4.29%)(P<0.01). The high expression rate of AEG-1 in tumor tissues was 55.71%, which was higher than that in adjacent normal tissues(7.86%)(P<0.01). The upregulated expression of mi R-4286 in NSCLC was correlated with tumor size, lymph node metastasis and TNM stage(all P<0.05), while the high expression of AEG-1 in NSCLC was associated with TNM stage and lymph node metastasis(both P<0.05). Moreover, Spearman analysis showed a positive correlation between mi R-4286 expression and AEG-1 expression in NSCLC(r=0.223, P=0.008). Conclusion The high expression of mi R-4286 and AEG-1 in NSCLC is correlated with TNM stage and lymph node metastasis, suggesting that both mi R-4286 and AEG-1 may be involved in the occurrence, development and metastasis of NSCLC.
引文
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[11] Su ZZ, Kang DC, Chen Y, et al. Identification and cloning of human astrocyte genes displaying elevated expression after infection with HIV-1or exposure to HIV-1 envelope glycoprotein by rapid subtraction hybridization, Ra SH[J]. Oncogene, 2002, 21(22):3592-3602. doi:10.1038/sj.onc.1205445.
[12] Ke Z, Mao X, Zeng C, et al. AEG-1 expression characteristics in human non-small cell lung cancer and its relationship with apoptosis[J]. Medical Oncology, 2013, 30(1):1-9. doi:10.1007/s12032-012-0383-9.
[2]王金秋,鲁杨,柯孔亮,等. miR-455-5p在结直肠癌中的表达及生物学特性[J].浙江医学, 2018, 40(8):796-802. doi:10.12056/j.issn.1006-2785.2017.40.8.2018-339.
[3] Wang X, Zhang Y, Zhi X. Correlation between microRNA expression, clinicopathological characteristics, and prognosis in patients with non-small cell lung cancer:A retrospective study[J]. Thoracic Cance r,2017, 8(5):511-516. doi:10.1111/1759-7714.12480.
[4] Liu F, Wang X, Li J, et al. miR-34c-3p functions as a tumour suppressor by inhibiting e IF 4E expression in non-small cell lung cancer[J]. Cell Proliferation, 2015, 48(5):582-592. doi:10.1111/cpr.12201.
[5]马志红,陈莹蓉,董顺利,等. NSCLC中AEG-1的表达及与临床病理特征和血管生成的关系研究[J].浙江医学, 2017, 39(8):617-619, 623.doi:10.12056/j.issn.1006-2785.2017.39.8.2017-293.
[6] Qu H, Zheng L, Pu J, et al. miRNA-558 promotes tumorigenesis and aggressiveness of neuroblastoma cells through activating the transcription of heparanase[J]. Human Molecular Genetics, 2015, 24(9):2539-2551. doi:10.1093/hmg/ddv018.
[7] Goff LA, Davila J, Swerdel MR, et al. Ago2 immunoprecipitation identifies predicted microRNAs in human embryonic stem cells and neural precursors[J]. PLoS One, 2009, 4(9):e7192. doi:10.1371/journal.pone.0007192.
[8] Komina A, Palkina N, Aksenenko M, et al. Antiproliferative and pro-apoptotic effects of MiR-4286 inhibition in melanoma cells[J]. PLoS One, 2016, 11(12):e0168229. doi:10.1371/journal.pone.0168229.
[9] Zhai R, Wei Y, Su L, et al. Whole-miRNome profiling identifies prognostic serum miRNAs in esophageal adenocarcinoma:the influence of Helicobacter pylori infection status[J]. Carcinogenesis, 2014, 36(1):87-93. doi:10.1093/carcin/bgu228.
[10] Zhang M, Tian H, Li R, et al. MicroRNA-4286 promotes esophageal carcinoma development by targeting INPP4A to evoke the JAK2/STAT3 pathway activation[J]. Pharmazie, 2018, 73(6):342-348. doi:10.1691/ph.2018.7339.
[11] Su ZZ, Kang DC, Chen Y, et al. Identification and cloning of human astrocyte genes displaying elevated expression after infection with HIV-1or exposure to HIV-1 envelope glycoprotein by rapid subtraction hybridization, Ra SH[J]. Oncogene, 2002, 21(22):3592-3602. doi:10.1038/sj.onc.1205445.
[12] Ke Z, Mao X, Zeng C, et al. AEG-1 expression characteristics in human non-small cell lung cancer and its relationship with apoptosis[J]. Medical Oncology, 2013, 30(1):1-9. doi:10.1007/s12032-012-0383-9.