Identification of deregulation of apoptosis and cell cycle in neuroendocrine tumors of the lung via NanoString nCounter expression analysis.
Identification of deregulation of apoptosis and cell cycle in neuroendocrine tumors of the lung via NanoString nCounter expression analysis.
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DOI：
10.18632/oncotarget.3992
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发表时间：
2015-09-22
期刊：
影响因子：
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通讯作者：
Mairinger FD
中科院分区：
文献类型：
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作者：
Walter RF;Werner R;Ting S;Vollbrecht C;Theegarten D;Christoph DC;Schmid KW;Wohlschlaeger J;Mairinger FD
肺的神经内分泌肿瘤包括典型（TC）和非典型类癌（AC）、大细胞神经内分泌癌（LCNEC）和小细胞肺癌（SCLC）。细胞周期和凋亡是多细胞稳态的关键途径，这些途径的失调与癌症发生有关。使用NanoString技术，将60份代表性FFPE标本（16份TC、13份AC、16份LCNEC和15份SCLC）用于mRNA表达分析。研究了8个与细胞凋亡相关的基因和10个调控细胞周期关键点的基因。ASCL 1、BCL 2、CASP 8、CCNE 1、CDK 1、CDK 2、CDKN 1A和CDKN 2A在类癌中的表达低于癌。相比之下，CCNE 1和CDK 6在类癌中的表达高于癌。计算的BCL 2/BAX比率显示从TC到SCLC的增加值。CDK 2、CDKN 1B、CDKN 2A和PNN在SCLC和LCNEC中的表达差异有统计学意义，其中SCLC中的表达高于LCNEC。类癌增加了CDK 4/6和CCND 1的表达，通过这种信号级联控制RB 1磷酸化。CDK 2和CCNE 1在癌中增加，表明它们使用相反的方式来控制RB 1。BAX和BCL 2是调节细胞凋亡的拮抗剂。从TC到SCLC，随着肿瘤恶性程度的增加，BCL 2的表达高于BAX的表达。
Neuroendocrine tumors of the lung comprise typical (TC) and atypical carcinoids (AC), large-cell neuroendocrine cancer (LCNEC) and small-cell lung cancer (SCLC). Cell cycle and apoptosis are key pathways of multicellular homeostasis and deregulation of these pathways is associated with cancerogenesis. Sixty representative FFPE-specimens (16 TC, 13 AC, 16 LCNEC and 15 SCLC) were used for mRNA expression analysis using the NanoString technique. Eight genes related to apoptosis and ten genes regulating key points of cell cycle were investigated. ASCL1, BCL2, CASP8, CCNE1, CDK1, CDK2, CDKN1A and CDKN2A showed lower expression in carcinoids compared to carcinomas. In contrast, CCNE1 and CDK6 showed elevated expression in carcinoids compared to carcinomas. The calculated BCL2/BAX ratio showed increasing values from TC to SCLC. Between SCLC and LCNEC CDK2, CDKN1B, CDKN2A and PNN expression was significantly different with higher expression in SCLC. Carcinoids have increased CDK4/6 and CCND1 expression controlling RB1 phosphorylation via this signaling cascade. CDK2 and CCNE1 were increased in carcinomas showing that these use the opposite way to control RB1. BAX and BCL2 are antagonists in regulating apoptosis. BCL2 expression increased over BAX expression with increasing malignancy of the tumor from TC to SCLC.