PD-L1 mRNA expression in EGFR-mutant lung adenocarcinoma
PD-L1 mRNA expression in EGFR-mutant lung adenocarcinoma
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DOI：
10.3892/or.2018.6442
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发表时间：
2018-07-01
期刊：
影响因子：
4.2
通讯作者：
Homma, Sakae
中科院分区：
文献类型：
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作者：
Isobe, Kazutoshi;Kakimoto, Atsushi;Homma, Sakae
在表皮生长因子受体 (EGFR) 突变型肺腺癌患者中，人们对程序性死亡配体 1 (PD-L1) mRNA 表达的分子机制以及细胞凋亡和生物标志物的作用知之甚少。对 33 名接受吉非替尼治疗的术后复发 EGFR 突变肺腺癌患者（16 例外显子 19 缺失、15 例 L858R、2 例 G719C）进行了研究。通过 PCR 定量福尔马林固定石蜡包埋的瘤旁和瘤内组织的 PD-L1 mRNA 表达。确定 PD-L1 mRNA 表达与 BIM、p53 上调细胞凋亡模块 (PUMA)、人表皮生长因子受体 2 (HER2)、间质-上皮转化 (MET)、EGFR 和血管内皮生长因子 A (VEGFA) 的相关性。 33 名患者中的 11 名 (33.3%) 和 14/33 名患者 (42.4%) 分别表达瘤内和瘤旁 PD-L1 mRNA。与瘤旁PD-L1 mRNA表达的患者相比，瘤内PD-L1 mRNA表达的患者BIM显着升高，VEGFA表达显着降低（P=0.049，P=0.009）。 PD-L1 mRNA 表达量与 PUMA、HER2、EGFR、MET 表达量无关，与 BIM 表达量呈正相关（r=0.41，P=0.017），与 VEGFA 表达量呈负相关（r=-0.33，P=0.043）。与无 PD-L1 表达的患者相比，瘤内 PD-L1 mRNA 表达的患者在吉非替尼治疗后的中位无进展生存期 (PFS) 显着缩短（分别为 255 天和 732 天；P=0.032）。因此，EGFR 突变肺腺癌中的 PD-L1 mRNA 表达与 BIM 和 VEGFA mRNA 表达以及吉非替尼治疗后较短的 PFS 相关。
Molecular mechanisms of programmed death-ligand 1 (PD-L1) mRNA expression and roles of apoptosis and biomarkers are poorly understood in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma patients. Thirty-three patients with recurrent postoperative EGFR-mutant lung adenocarcinoma (exon 19 deletion in 16, L858R in 15, G719C in 2 patients) treated with gefitinib were studied. PD-L1 mRNA expression of formalin-fixed paraffin-embedded paratumoral and intratumoral tissues was quantified by PCR. Correlations of PD-L1 mRNA expression with BIM, p53 upregulated modular of apoptosis (PUMA), human epidermal growth factor receptor 2 (HER2), mesenchymal-epithelial transition (MET), EGFR, and vascular endothelial growth factor A (VEGFA) were determined. Eleven of the 33 patients (33.3%) and 14/33 patients (42.4%) expressed intratumoral and paratumoral PD-L1 mRNA, respectively. Patients with intratumoral PD-L1 mRNA expression had significantly higher BIM and lower VEGFA expression compared with paratumoral PD-L1 mRNA patients (P=0.049, P=0.009). PD-L1 mRNA expression was not associated with the expression of PUMA, HER2, EGFR and MET but was positively correlated with BIM expression (r=0.41, P=0.017) and inversely correlated with VEGFA expression (r=-0.33, P=0.043). Patients with intratumoral PD-L1 mRNA expression had significantly shorter median progression-free survival (PFS) after gefitinib therapy compared with no PD-L1 expression (255 vs. 732 days, respectively; P=0.032). Thus, PD-L1 mRNA expression in EGFR-mutant lung adenocarcinoma was associated with BIM and VEGFA mRNA expression and with shorter PFS after gefitinib therapy.