a Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine , Shanghai Jiao Tong University , Shanghai , China.
b The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital , Shanghai Jiaotong University School of Medicine , Shanghai , China.
Cell Cycle. 2018;17(17):2164-2174. doi: 10.1080/15384101.2018.1520558. Epub 2018 Sep 22.
The highly malignant feature and difficulties for early diagnosis are the key reasons contributing to the poor prognosis of pancreatic cancer (PC) patients. NFE2L3 is a nuclear transcription factor, which has been reported an important biomarker of several tumors. But the role of NFE2L3 in PC remained undefined. Herein, through qPCR and immunohistochemistry, we found a significantly increased NFE2L3 in PC tissues as compared with adjacent non-tumor tissues. While reducing NFE2L3 expression suppressed the invasion abilities of PC cells, elevated NFE2L3 was found associated with lymph node metastasis (P = 0.001; HR = 3.95; 95% CI: 1.70 - 9.17) and advanced TNM stages (P < 0.001; HR = 4.06; 95% CI: 1.74 - 9.46). Consistently, data from both our two cohorts and the TCGA database revealed that higher NFE2L3 PC carriers had worse outcomes than those lower NFE2L3 expressers. Lastly, we confirmed the regulatory role of NFE2L3 on VEGFA, an important player involved in tumor angiogenesis. Collectively, our investigations suggested the oncogenic role of NFE2L3 in PC development and provided the rational for future adding NFE2L3 for the risk assessment of PC patients.
NFE2L3: NF-E2-related factor 3; UHMK1: U2AF homology motif kinase 1; VEGFA: vascular endothelial growth factor A; GEO: gene expression omnibus; TCGA: The Cancer Genome Atlas; HPDE: human pancreas duct cells; OS: overall survival; IHC: immunohistochemistry; FFPE: formalin-fixed and paraffin-embedded; SEM: standard error of mean.
高度恶性特征和早期诊断困难是导致胰腺癌（PC）患者预后不良的关键原因。NFE2L3 是一种核转录因子，已被报道为几种肿瘤的重要生物标志物。但是 NFE2L3 在 PC 中的作用仍未确定。在此，通过 qPCR 和免疫组织化学，我们发现与相邻非肿瘤组织相比，PC 组织中 NFE2L3 的表达显著增加。而降低 NFE2L3 的表达抑制了 PC 细胞的侵袭能力，而升高的 NFE2L3 与淋巴结转移（P=0.001；HR=3.95；95%CI：1.70-9.17）和晚期 TNM 分期（P<0.001；HR=4.06；95%CI：1.74-9.46）相关。一致地，我们的两个队列和 TCGA 数据库的数据表明，NFE2L3 高表达的 PC 患者的预后比 NFE2L3 低表达者差。最后，我们证实了 NFE2L3 对 VEGFA 的调节作用，VEGFA 是肿瘤血管生成中重要的参与者。总之，我们的研究表明 NFE2L3 在 PC 发展中的致癌作用，并为未来将 NFE2L3 用于 PC 患者的风险评估提供了依据。
NFE2L3：NF-E2 相关因子 3；UHMK1：U2AF 同源基序激酶 1；VEGFA：血管内皮生长因子 A；GEO：基因表达综合数据库；TCGA：癌症基因组图谱；HPDE：人胰腺导管细胞；OS：总生存期；IHC：免疫组织化学；FFPE：福尔马林固定和石蜡包埋；SEM：均数的标准误差。
