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中华肺部疾病杂志(电子版)

中华肺部疾病杂志(电子版) ›› 2020, Vol. 13 ›› Issue (02) : 242 -246. doi: 10.3877/cma.j.issn.1674-6902.2020.02.023

论著

HIF-1α、PD-L1与非小细胞肺癌淋巴转移的相关性
齐倩1,†(), 王春梅1, 杨娟1, 田英1, 冯超1   
  1. 1. 061000　沧州，沧州市人民医院肿瘤内科
  • 收稿日期:2019-10-25 出版日期:2020-04-25
  • 通信作者: 齐倩
  • 基金资助:
    国家自然科学基金资助项目(81671277); 沧州市科技计划项目(162302042)

Correlation between HIF-1α, PD-L1 and lymphatic metastasis in non-small cell lung cancer

qian Qi1,†(), Chunmei Wang1, Juan Yang1, Ying Tian1, Chao Feng1   

  1. 1. Department of oncology, Cangzhou people′s Hospital, Cangzhou 061000, China
  • Received:2019-10-25 Published:2020-04-25
  • Corresponding author: qian Qi
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齐倩, 王春梅, 杨娟, 田英, 冯超. HIF-1α、PD-L1与非小细胞肺癌淋巴转移的相关性[J]. 中华肺部疾病杂志(电子版), 2020, 13(02): 242-246.

qian Qi, Chunmei Wang, Juan Yang, Ying Tian, Chao Feng. Correlation between HIF-1α, PD-L1 and lymphatic metastasis in non-small cell lung cancer[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2020, 13(02): 242-246.

目的

探讨HIF-1α、PD-L1表达水平与非小细胞肺癌(NSCLC)患者淋巴转移风险的相关性。

方法

选择2015年12月至2017年12月于我院手术治疗且未发生淋巴结转移的NSCLC患者97例。免疫组化分析对所有患者癌症病灶中HIF-1α、PD-L1的表达量进行检测。而后进行为期24月的随访，记录淋巴转移发生情况。根据HIF-1α及PD-L1表达量对所有患者进行分组，分析随访期间两种蛋白不同表达量患者淋巴转移风险之间的差异。通过COX回归分析确定NSCLC淋巴结转移之间的危险因素。

结果

所有患者平均随访时间19(12，24)月，共计92例患者完成随访，发生淋巴结转移例数36例，淋巴结转移率39.13%，淋巴结未转移中位时间时间24(16，24)月。HIF-1α高表达及低表达患者淋巴结转移率巴结转移发生率分别为92.6%和26.9%，HIF-1α高表达患者淋巴结转移率显著高于低表达患者(log-rankχ2＝63.052；P<0.001)。PD-L1高表达及低表达患者淋巴结转移发生率分别为82.1%和21.3%，PD-L1高表达患者淋巴结转移率显著高于低表达患者(log-rankχ2＝39.555；P<0.001)。HIF-1α高表达(HR＝25.790，95%CI＝10.005-30.287)、PD-L1高表达(HR＝16.693，95%CI＝12.014-20.356)、CEA(HR＝1.058，95%CI＝1.013-1.106)是NSCLC患者淋巴转移的危险因素(P<0.05)。

结论

HIF-1α、PD-L1高表达与NSCLC患者淋巴转移风险具有显著相关性，可作为早期预测和治疗的靶点。

关键词: HIF-1α, PD-L1, 非小细胞肺癌, 淋巴结转移
Objective

To investigate the correlation between the expression levels of HIF-1α and PD-L1 and the risk of lymphatic metastasis in patients with non-small cell lung cancer (NSCLC).

Methods

A total of 97 NSCLC patients who underwent surgical treatment in our hospital from December 2015 to December 2017 without lymph node metastasis were selected. Immunohistochemical analysis was used to detect the expression of HIF-1α and PD-L1 in cancer lesions of all patients. Then a follow-up period of 24 months was performed to record the occurrence of lymphatic metastases. All patients were grouped according to the expression levels of HIF-1α and PD-L1, and the differences in the risk of lymphatic metastasis in patients with different expression levels of the two proteins during the follow-up period were analyzed. COX regression analysis was used to determine the relationship between HIF-1α and PD-L1 and NSCLC lymph node metastasis.

Results

All patients were followed up for an average of 19 (12, 24) months. A total of 92 patients completed the follow-up. 36 cases of lymph node metastasis occurred. The rate of lymph node metastasis was 39.13%. Lymph node metastasis rates in patients with high and low expression of HIF-1α were 92.6% and 26.9%, respectively. Lymph node metastasis rates in patients with high expression of HIF-1α were significantly higher than those in patients with low expression (log-rankχ2=63.052; P<0.001) . The incidence of lymph node metastasis in patients with high PD-L1 expression and low expression was 82.1% and 21.3%, respectively. The lymph node metastasis rate in patients with high PD-L1 expression was significantly higher than that in patients with low expression (log-rankχ2=39.555; P<0.001). HIF-1α high expression (HR=25.790, 95%CI=10.005-30.287), PD-L1 high expression (HR=16.693, 95%CI=12.014-20.356), CEA (HR=1.058, 95%CI=1.013-1.106) is a risk factor for lymphatic metastasis in patients with NSCLC (P<0.05).

Conclusion

The high expression of HIF-1α and PD-L1 has significant correlation with the risk of lymphatic metastasis in patients with NSCLC, and can be used as targets for early prediction and treatment.

Key words: HIF-1α, PD-L1, Non-small cell lung cancer, Lymph node metastasis
图1 HIF-1α表达量对于NSCLC患者淋巴结转移的影响
图2 PD-L1表达量对于NSCLC患者淋巴结转移的影响
表1 NSCLC患者淋巴结转移的影响因素分析
临床资料 转移(n＝36) 非转移(n＝56) HR(95%CI) P值
年龄(岁) 56.85±12．73 55.58±10．31 1.007(0.977～1.038) 0.657
性别构成(男/女) 17/21 24/22 1.116(0.603～2.232) 0.657
BMI(kg/m2) 20.81±2．41 21.49±1．92 0.899(0.796～1.052) 0.185
HIF-1α        
  低表达 11 54 10.324(4.985～21.380) <0.001
  高表达 25 2    
PD-L1        
  低表达 13 51 6.896(3.449～13.789) <0.001
  高表达 23 5    
TMN分期        
  Ⅰ 9 32 2.952(1.387～6.285) 0.005
  Ⅱ 27 24    
病理分型        
  腺癌 24 41 1.188(0.594～2.377) 0.626
  非腺癌 12 15    
CEA(ng/ml) 159.84±19．93 141.83±20．29 1.028(1.013～1.043) <0.001
肿瘤直径(cm) 3.68±1．12 2.68±1．10 1.712(1.286～2.279) <0.001
影像学特征        
  毛刺征 14 21 1.094(0.559～2.138) 0.793
  血管集束征 6 14 0.715(0.298～1.719) 0.454
  胸膜凹陷 10 19 1.527(0.736～3.168) 0.255
  空洞 7 19 0.532(0.233～1.216) 0.135
  支气管血管束增厚 4 10 1.098(0.481～2.507) 0.824
病灶位置(左右肺)        
  左肺 21 33 0.995(0.513～1.930) 0.995
  右肺 15 23    
病灶分叶        
  上叶 19 31 0.953(0.495～1.834) 0.885
  中、下叶 17 25    
表2 影响淋巴结转移的Cox回归分析结果
因　素 β 标准误 Wald P值 HR 95%CI
LL UL
HIF-1α高表达 3.25 1.021 10.138 0.001 25.790 10.005 30.287
PD-L1高表达 2.815 0.909 9.599 0.002 16.693 12.014 20.356
CEA 0.057 0.022 6.42 0.011 1.058 1.013 1.106
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