Ichinokawa Kazuomi, Nakanishi Yoshitsugu, Hida Yasuhiro, Tsuchikawa Takahiro, Kato Tatsuya, Itoh Tomoo, Kaji Mitsuhito, Kaga Kichizo, Hirano Satoshi
Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan.
Department of Cardiovascular and Thoracic Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan.
Oncol Lett. 2019 Jul;18(1):117-126. doi: 10.3892/ol.2019.10293. Epub 2019 Apr 30.
The aim of this study was to clarify the association between expression of human leukocyte antigen (HLA) class I in non-small-cell lung cancer (NSCLC) cells and patient survival. To address this, immunohistochemical staining for HLA class I was performed on specimens from 111 patients with NSCLC, and overall survival curves were compared using the log-rank test. In addition, multivariate analyses were performed using Cox's proportional hazard model. The cases were divided into 5 classes based on the expression of HLA class I heavy chain and β2-microglobulin. The overall survival rate for patients with tumors lacking HLA class I heavy chain (30 cases; 27.0%) was significantly decreased. The multivariate analysis demonstrated that the absence of HLA class I heavy chain was an independent predictor of poor prognosis. There was a trend towards an unfavorable prognosis for patients whose tumors did not express β2-microglobulin (57 cases; 51.4%). Downregulation of HLA class I heavy chain expression was significantly associated with the downregulation of β2-microglobulin. Cases lacking HLA class I heavy chain as well as β2-microglobulin expression (23 cases; 20.7%) had a statistically significant unfavorable prognosis compared with other cases. The present findings demonstrate that the lack of HLA class I heavy chain expression in tumor cells is an independent prognostic factor for poor NSCLC survival, and is likely to exert an important influence on immune surveillance in patients.
本研究的目的是阐明非小细胞肺癌(NSCLC)细胞中人类白细胞抗原(HLA)I类分子的表达与患者生存率之间的关联。为解决这一问题,对111例NSCLC患者的标本进行了HLA I类分子的免疫组织化学染色,并使用对数秩检验比较了总生存曲线。此外,使用Cox比例风险模型进行了多因素分析。根据HLA I类重链和β2-微球蛋白的表达将病例分为5类。缺乏HLA I类重链的患者(30例;27.0%)的总生存率显著降低。多因素分析表明,HLA I类重链缺失是预后不良的独立预测因素。肿瘤未表达β2-微球蛋白的患者(57例;51.4%)有预后不良的趋势。HLA I类重链表达下调与β2-微球蛋白下调显著相关。与其他病例相比,缺乏HLA I类重链以及β2-微球蛋白表达的病例(23例;20.7%)有统计学上显著的不良预后。目前的研究结果表明,肿瘤细胞中HLA I类重链表达缺失是NSCLC患者生存不良的独立预后因素,并且可能对患者的免疫监视产生重要影响。