非小细胞肺癌中KIR 2D（L1、L3、L4、S4）和KIR 3DL1蛋白表达
KIR 2D (L1, L3, L4, S4) and KIR 3DL1 protein expression in non-small cell lung cancer.
作者信息
He Yayi, Bunn Paul A, Zhou Caicun, Chan Dan
机构信息
Department of Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, People's Republic of China.
Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
出版信息
Oncotarget. 2016 Dec 13;7(50):82104-82111. doi: 10.18632/oncotarget.13486.
BACKGROUND
Nature killer (NK) cells are the immune system's first line of defense against both viral infections and tumors. Killer cell immunoglobulin-like receptors (KIRs) are associated with susceptibility to different types of cancers. We investigated KIR 2D (L1, L3, L4, S4) and KIR 3DL1 protein expression and their association with survival in non-small cell lung cancer (NSCLC).
METHODS
The expression of KIR 2D (L1, L3, L4, S4) (BC032422/ ADQ31987/ NP_002246/ NP_036446, ABCAM) and KIR 3DL1 (AA 1-444, ABCAM) protein was assessed by immunohistochemistry (IHC) in 62 NSCLC patients.
RESULTS
KIR 2D (L1, L3, L4, S4) and KIR 3DL1 were expressed both on NSCLC tumor cells and tumor infiltrating lymphocytes (TILs). Fourteen samples (22.6%) stained positive for KIR 2D (L1, L3, L4, S4) on the tumor cells, and 10 (16.1%) had positive expression on the TILs. Thirty-three samples (53.2%) stained positive for KIR 3DL1 on the tumor cells, and 31 (50.0%) had positive expression on the TILs. Patients with negative KIR 2D (L1, L3, L4, S4) expression on tumor cells or TILs had longer overall survival (OS) than patients who are KIR 2D (L1, L3, L4, S4) positive on tumor cells (40.70 weeks, 95% CI 24.76-56.65 vs. 7.10 weeks, 95% CI 0.00-19.38, P = 0.014) or TILs (40.70 weeks, 95% CI 24.05-57.35 vs. 3.90 weeks, 95% CI 0.00-9.17, P < 0.001). Likewise, longer OS was significantly correlated with negative expression of KIR 3DL1 on tumor cells (62.30 weeks, 95% CI 0.00-177.37 vs. 13.10 weeks, 95% CI 3.42-22.78, P < 0.001) or TILs (62.30 weeks, 95% CI 0.00-152.05 vs. 12.10 weeks, 95% CI 2.61-21.59, P < 0.001). Cox regression analysis showed that KIR 2D (L1, L3, L4, S4) on TILs was correlated with OS (P = 0.032, Odds Ratio 2.628 95%CI 1.089-6.340).
CONCLUSIONS
KIR 2D (L1, L3, L4, S4) and KIR 3DL1 expression was correlated with poor prognosis in NSCLC patients.
背景
自然杀伤（NK）细胞是免疫系统抵御病毒感染和肿瘤的第一道防线。杀伤细胞免疫球蛋白样受体（KIRs）与不同类型癌症的易感性相关。我们研究了KIR 2D（L1、L3、L4、S4）和KIR 3DL1蛋白表达及其与非小细胞肺癌（NSCLC）患者生存的关系。
方法
采用免疫组织化学（IHC）方法检测62例NSCLC患者中KIR 2D（L1、L3、L4、S4）（BC032422/ADQ31987/NP_002246/NP_036446，ABCAM）和KIR 3DL1（AA 1 - 444，ABCAM）蛋白的表达。
结果
KIR 2D（L1、L3、L4、S4）和KIR 3DL1在NSCLC肿瘤细胞和肿瘤浸润淋巴细胞（TILs）上均有表达。14个样本（22.6%）肿瘤细胞上KIR 2D（L1、L3、L4、S4）染色呈阳性，10个样本（16.1%）TILs上有阳性表达。33个样本（53.2%）肿瘤细胞上KIR 3DL1染色呈阳性，31个样本（50.0%）TILs上有阳性表达。肿瘤细胞或TILs上KIR 2D（L1、L3、L4、S4）表达阴性的患者总生存期（OS）长于肿瘤细胞上KIR 2D（L1、L3、L4、S4）呈阳性的患者（40.70周，95%CI 24.76 - 56.65 vs. 7.10周，95%CI 0.00 - 19.38，P = 0.014）或TILs上呈阳性的患者（40.70周，95%CI 24.05 - 57.35 vs. 3.90周，95%CI 0.00 - 9.17，P < 0.001）。同样，OS较长与肿瘤细胞上KIR 3DL1阴性表达显著相关（62.30周，95%CI 0.00 - 177.37 vs. 13.10周，95%CI 3.42 - 22.78，P < 0.001）或TILs上阴性表达相关（62.30周，95%CI 0.00 - 152.05 vs. 12.10周，95%CI 2.61 - 21.59，P < 0.001）。Cox回归分析显示TILs上的KIR 2D（L1、L3、L4、S4）与OS相关（P = 0.032，比值比2.628，95%CI 1.089 - 6.340）。
结论
KIR 2D（L1、L3、L4、S4）和KIR 3DL1表达与NSCLC患者预后不良相关。
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