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PD-L1表达及PD-L1基因多态性与肺腺癌和肺鳞癌预后不良的相关性

Association of PD-L1 expression and PD-L1 gene polymorphism with poor prognosis in lung adenocarcinoma and squamous cell carcinoma.

作者信息

Yeo Min-Kyung, Choi Song-Yi, Seong In-Ock, Suh Kwang-Sun, Kim Jin Man, Kim Kyung-Hee

机构信息

Department of Pathology, Cancer Research Institute, Chungnam National University, School of Medicine, Daejeon, Republic of Korea.

Department of Pathology, Cancer Research Institute, Chungnam National University, School of Medicine, Daejeon, Republic of Korea.

出版信息

Hum Pathol. 2017 Oct;68:103-111. doi: 10.1016/j.humpath.2017.08.016. Epub 2017 Aug 26.

Abstract

Programmed cell death 1 receptor (PD-1)/programmed death-1 ligand-1 (PD-L1) interaction has been linked to tumor immune evasion. PD-L1 expression has been indicated in identifying non-small cell lung carcinoma (NSCLC) patients for treatment with anti-PD-1 or anti-PD-L1 therapy. The goal of this study was to evaluate the clinicopathologic values of PD-L1 expression and single-nucleotide polymorphisms (SNPs) in the PD-L1 gene in lung adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). The 147 NSCLC tissues consisted of 84 samples of ADC and 63 samples of SqCC. All tissue microarray paraffin blocks were used for PD-L1 immunohistochemical assays with 22C3, SP263, and SP142 clones. Three SNPs in the PD-L1 gene, rs4143815, rs822336, and rs822337, were genotyped using SNP pyrosequencing. The PD-L1 expression was significantly higher in SqCC than in ADC. Among ADCs, PD-L1 expression was significantly higher in papillary and solid types than in lepidic and acinar types. Statistical associations of the PD-L1 expression with a shorter disease-free survival outcome and lymph node metastasis in the ADCs were found but no associations in SqCCs. Among the three SNPs, the rs4143815 genotype CC was statistically associated with positive 22C3 PD-L1 labeling in NSCLCs. The rs4143815 genotype GG instead showed a trend of shorter survival outcomes but did not reach statistical significance in the ADCs. Our results showed a significantly higher prevalence of positive PD-L1 expression in lung SqCC than in ADC. However, the PD-L1 expression and rs4143815 genotype GG might be useful for the prediction of poor prognosis in lung ADC cases.

摘要

程序性细胞死亡1受体(PD-1)/程序性死亡配体1(PD-L1)相互作用与肿瘤免疫逃逸相关。PD-L1表达已被用于识别非小细胞肺癌(NSCLC)患者以进行抗PD-1或抗PD-L1治疗。本研究的目的是评估肺腺癌(ADC)和肺鳞状细胞癌(SqCC)中PD-L1表达及PD-L1基因单核苷酸多态性(SNP)的临床病理价值。147例NSCLC组织包括84例ADC样本和63例SqCC样本。所有组织微阵列石蜡块均用于采用22C3、SP263和SP142克隆进行的PD-L1免疫组织化学检测。使用SNP焦磷酸测序法对PD-L1基因中的三个SNP(rs4143815、rs822336和rs822337)进行基因分型。SqCC中的PD-L1表达显著高于ADC。在ADC中,乳头型和实体型的PD-L1表达显著高于鳞屑型和腺泡型。在ADC中发现PD-L1表达与较短的无病生存结局及淋巴结转移存在统计学关联,但在SqCC中未发现此类关联。在这三个SNP中,rs4143815基因型CC与NSCLC中22C3 PD-L1阳性标记存在统计学关联。相反,rs4143815基因型GG在ADC中显示出较短生存结局的趋势,但未达到统计学显著性。我们的结果显示,肺SqCC中PD-L1阳性表达的患病率显著高于ADC。然而,PD-L1表达和rs4143815基因型GG可能有助于预测肺ADC病例的不良预后。

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