Hu Zhangguo, Gu Xiang, Zhong Runbo, Zhong Hua
Department of Pulmonary Disease, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
Department of Emergency, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
J Thorac Dis. 2018 Apr;10(4):2089-2099. doi: 10.21037/jtd.2018.03.148.
The present study aimed to investigate the association of CD45RO, CD8, CCR7 and FOXP3 tumor-infiltrating lymphocytes (TILs) with the clinicopathological features as well as survival of patients with lung adenocarcinoma.
Ninety patients with lung adenocarcinoma who underwent surgery were recruited in the present study. Lung adenocarcinoma tissues and paired adjacent lung tissues were obtained from all participants, and immunohistochemistry was performed to detect the expression of CD45RO, CD8, CCR7 and FOXP3. After multiplying the staining intensity score by the labeling frequency score, the immunohistochemical results were divided into three groups: TILs low, TILs intermediate and TILs high.
CD45RO, CD8 and CCR7 infiltrating lymphocytes were markedly increased in lung adenocarcinoma (all P<0.001) while FOXP3 infiltrating lymphocytes were reduced (P<0.001) compared with than in adjacent tissues. CD45RO TILs were negatively associated with tumor size (P=0.002), lymph node metastasis (P<0.001) and TNM stage (P<0.001). CD8 TILs were also negatively correlated with lymph node metastasis (P=0.016). Kaplan-Meier curve analysis revealed that CD45RO TILs were positively associated with longer disease-free survival (DFS) (P<0.001) and overall survival (OS) (P<0.001). Univariate and multivariate Cox's proportional hazards regression confirmed that CD45RO TILs (high) independently predicted longer DFS (P=0.002) and OS (P=0.009).
The present study demonstrates that CD45RO TILs are negatively correlated with tumor size, lymph node metastasis and TNM stage and that CD45RO TILs (high) can be regarded as a novel and promising biomarker for prolonged DFS and OS in lung adenocarcinoma patients.
本研究旨在探讨CD45RO、CD8、CCR7和FOXP3肿瘤浸润淋巴细胞(TILs)与肺腺癌患者临床病理特征及生存情况之间的关联。
本研究招募了90例行手术治疗的肺腺癌患者。从所有参与者处获取肺腺癌组织及配对的相邻肺组织,并进行免疫组织化学检测以检测CD45RO、CD8、CCR7和FOXP3的表达。将染色强度评分与标记频率评分相乘后,免疫组化结果分为三组:低TILs组、中TILs组和高TILs组。
与相邻组织相比,肺腺癌中CD45RO、CD8和CCR7浸润淋巴细胞明显增加(均P<0.001),而FOXP3浸润淋巴细胞减少(P<0.001)。CD45RO TILs与肿瘤大小(P=0.002)、淋巴结转移(P<0.001)和TNM分期(P<0.001)呈负相关。CD8 TILs也与淋巴结转移呈负相关(P=0.016)。Kaplan-Meier曲线分析显示,CD45RO TILs与更长的无病生存期(DFS)(P<0.001)和总生存期(OS)(P<0.001)呈正相关。单因素和多因素Cox比例风险回归证实,CD45RO TILs(高)独立预测更长的DFS(P=0.002)和OS(P=0.009)。
本研究表明,CD45RO TILs与肿瘤大小、淋巴结转移和TNM分期呈负相关,且CD45RO TILs(高)可被视为肺腺癌患者延长DFS和OS的一种新的有前景的生物标志物。