Li Hao-Ran, Gao Jian, Jin Chun, Jiang Jia-Hao, Ding Jian-Yong
Department of Thoracic Surgery, Zhongshan Hospital, Fudan University Shanghai 200032, P. R. China.
Am J Transl Res. 2020 Feb 15;12(2):447-462. eCollection 2020.
SET binding protein 1 (SETBP1) has involved in cancer pathogenesis like leukemic malignancies and breast cancer. But the role and the underlying mechanism in NSCLC remain unclear.
RT-PCR and western blotting were used for determining the expression level of SETBP1 in NSCLC. The clinical values of SETBP1 expression were evaluated by tissue microarray and immunohistochemistry. CCK-8, transwell and Matrigel assays were used to assess NSCLC cells proliferation, migration and invasion ability. The analysis of EMT markers was carried out by RT-PCR, western blotting and immunofluorescence. Bioinformatics analysis revealed the relationship between SETBP1 expression and tumor-associated immune cells.
SETBP1 expression was significantly downregulated in NSCLC tissues than matched peri-tumors and NSCLC patients with the decreased level of SETBP1 had worse OS. Downregulation of SETBP1 expression induced EMT to promote NSCLC cells proliferation, migration and invasion by the activation of ERK1/2 signal pathway. Aberrant SETBP1 expression was companied by disordered immune status of NSCLC patients and might be involved in regulation of polarization of tumor-associated macrophages.
SETBP1 can act as a tumor suppressor to reduce the progression of NSCLC and can be used for a prognostic biomarker in NSCLC. Aberrant SETBP1 expression was companied by disordered immune status of NSCLC patients.
SET结合蛋白1（SETBP1）参与白血病和乳腺癌等癌症的发病机制。但其在非小细胞肺癌（NSCLC）中的作用及潜在机制尚不清楚。
采用逆转录-聚合酶链反应（RT-PCR）和蛋白质免疫印迹法检测NSCLC中SETBP1的表达水平。通过组织芯片和免疫组织化学评估SETBP1表达的临床价值。采用细胞计数试剂盒-8（CCK-8）、Transwell和基质胶实验评估NSCLC细胞的增殖、迁移和侵袭能力。通过RT-PCR、蛋白质免疫印迹法和免疫荧光分析上皮-间质转化（EMT）标志物。生物信息学分析揭示SETBP1表达与肿瘤相关免疫细胞之间的关系。
与配对的癌旁组织相比，SETBP1在NSCLC组织中的表达显著下调，且SETBP1水平降低的NSCLC患者总生存期较差。SETBP1表达下调通过激活细胞外信号调节激酶1/2（ERK1/2）信号通路诱导EMT，促进NSCLC细胞的增殖、迁移和侵袭。SETBP1表达异常与NSCLC患者免疫状态紊乱有关，可能参与肿瘤相关巨噬细胞极化的调节。
SETBP1可作为肿瘤抑制因子，减缓NSCLC的进展，可作为NSCLC的预后生物标志物。SETBP1表达异常与NSCLC患者免疫状态紊乱有关。
