肿瘤细胞和免疫细胞PD-1在早期肺腺癌中的表达及其预后价值

Expression and Prognostic Value of PD⁃1 of Tumor or Immune Cancer Cells in Early⁃Stage Lung Adenocarcinoma

目的既往关于肿瘤细胞程序性死亡配体1(programmed cell death⁃ligand 1,PD⁃L1)的分子机制及其临床价值已经被广泛探索,而关于肿瘤细胞及免疫细胞程序性细胞死亡1(programmed cell death⁃1,PD⁃1)的研究仍然缺乏,本文旨在探究早期肺腺癌患者肿瘤组织中免疫细胞、肿瘤细胞PD⁃1蛋白表达及其与临床病理特征、复发风险的相关性。方法本研究纳入2010年4月至2021年6月于广东省人民医院就诊的早期肺腺癌患者,并用免疫组化方法对石蜡包埋肿瘤组织上的肿瘤细胞及其周围免疫细胞进行PD⁃1蛋白表达检测。结果本研究共纳入446例早期肺腺癌患者,肿瘤细胞PD⁃1阳性率为2.2%(10/446),免疫细胞PD⁃1阳性率为18.2%(81/446)。二元logistics回归分析结果显示:免疫细胞PD⁃1阳性表达在吸烟患者(对比非吸烟者)中更常见[比值比(odds ratio,OR)2.059,95%可信区间(confidence interval,CI)1.138~3.723,P<0.05],肿瘤细胞PD⁃1阳性表达在Ⅲ期(对比Ⅰ期)的患者中更常见(OR:45.92,95%CI 5.616~375.507,P<0.05),并且肿瘤细胞PD⁃1表达与免疫细胞PD⁃1表达之间呈正相关(r=0.58,P<0.05)。Kaplan⁃Meier生存分析显示,肿瘤细胞PD⁃1阳性患者复发风险更高[风险比(hazard ratio,HR)6.5,95%CI 1.227~34.590,无病生存率(disease⁃free survival,DFS):P<0.05],免疫细胞PD⁃1表达与复发风险无关(DFS:P=0.26)。结论肿瘤细胞PD⁃1阳性表达可能是早期肺腺癌患者术后的不良预后因子。

Objective The molecular mechanism of programmed cell death⁃ligand 1(PD⁃L1)in tumor cells and its clinical value had been widely explored.However,the research of programmed cell death⁃1(PD⁃1)on tumor cells and immune cells was still lacking.Our article aimed to explore the PD⁃1 expression on immune cells and tumor cells respectively.Otherwise,we also explored the correlation of PD⁃1 and clinicopathological features,and its recurrence risk in patients with early⁃stage lung adenocarcinoma.Methods In this study,patients with early⁃stage lung adenocarcinoma were enrolled from Guangdong Provincial People􀆳s Hospital between April 2010 and June 2021.PD⁃1 protein expression was assessed by immunohistochemical(IHC)on tumor cells and immune cells,respectively.Results 446 early⁃stage lung adenocarcinoma patients meeting the criteria were analyzed.The positive expression rate of PD⁃1 on tumor cells was 2.2%(10/446),and the positive expression rate of PD⁃1 on immune cells was 18.2%(81/446).Binary logistics regression analysis showed that positive PD⁃1 expression on immune cells was more likely to happen in smoking patients(vs.non⁃smoker)[odds ratio(OR)2.059,95%confidence interval(CI)1.138~3.723,P<0.05],PD⁃1 positive expression on tumor cells are more likely to happen in stageⅢpatients(vs.stageⅠ)(OR:45.92,95%CI 5.616~375.507,P<0.05),and there was a positive correlation between PD⁃1 expression on tumor cells and PD⁃1 expression on immune cells(r=0.58,P<0.05).Kaplan⁃Meier survival analysis showed that the patients of tumor cell PD⁃1 positive expression had a higher risk of recurrence[hazard ratio(HR)6.5,95%CI 1.227~34.590,disease⁃free survival(DFS):P<0.05],and PD⁃1 expression on immune cells was not related to the risk of recurrence(DFS:P=0.26).Conclusions The positive expression of PD⁃1 on tumor cells may be a poor prognostic factor after surgery in patients with early⁃stage lung adenocarcinoma.