摘要
目的探讨外周血中12种细胞因子(IL-1β、IL-1Ra、IL-4、IL-6、IL-13、IL-17、Eotaxin、IP-10、MCP-1、RANTES、G-CSF、PDGF-BB)在不同肿瘤类型、年龄、性别及季节的表达差异,系统解析机体免疫状态,为肿瘤免疫治疗提供新思路。方法回顾性纳入2016年3月~2023年7月于解放军总医院就诊的1842例恶性肿瘤患者临床资料,所有患者均完成外周血细胞因子检测。入组患者的肿瘤类型包括肺癌、肝癌、胃癌、乳腺癌、结直肠癌、胰腺癌、卵巢癌和食管癌。其中男性1266例、女性576例;年龄25~92岁。季节分为春季(3~5月)、夏季(6~8月)、秋季(9~11月)、冬季(12~2月)。比较不同肿瘤类型间细胞因子表达差异及同类型肿瘤中细胞因子随年龄、性别、季节的变化及相关性。结果IL-1Ra、IL-13、IL-17、Eotaxin、G-CSF、IP-10、MCP-1、PDGF-BB和RANTES 9种细胞因子在8种肿瘤中的表达均呈现瘤种差异,差异均有统计学意义(χ^(2)=36.17、21.75、40.02、32.19、28.67、19.08、48.75、26.62、21.37,P<0.001)。其中,IL-1Ra在胰腺癌显著低表达;IL-13在结直肠癌较肝癌升高;IL-17在卵巢癌高表达,而在食管癌低表达;RANTES在肺癌高表达;MCP-1在食管癌高表达;Eotaxin在卵巢癌高表达、肺癌低表达;IP-10在肺癌浓度显著高于结直肠癌;PDGF-BB在胰腺癌低表达;G-CSF在食管癌上调,胰腺癌下调。而IL-1β、IL-4、IL-63种细胞因子在8种肿瘤中的表达差异均无统计学意义(P>0.05)。细胞因子表达与年龄也呈现相关性,IL-4在乳腺癌中与年龄呈正相关(r=0.306,P<0.001);IP-10在肺癌和结直肠癌中与年龄呈弱正相关(r=0.127、0.294,P<0.001);Eotaxin在肺癌、肝癌、乳腺癌及结直肠癌中均随年龄升高(r=0.102、0.301、0.506、0.265,P<0.05);PDGF-BB在肝癌、胃癌、乳腺癌及结直肠癌中呈年龄依赖性下调(r=-0.284、-0.168、-0.316、-0.308,P<0.001)。细胞因子的性别差异性显示,男性肺癌的Eotaxin、肝癌的PDGF-BB、胃癌的G-CSF显著高于女性(Z=-2.29、-3.98、-2.71,P<0.05);女性肝癌的IL-4、IL-17、Eotaxin、IP-10及胃癌的RANTES均显著高于男性(Z=-2.9、-3.63、-3.39、-2.94、-2.71,P<0.05)。细胞因子的季节特征显示,肺癌IL-1β、IL-17水平呈夏季高[0.60(0.16,1.77)、20.29(13.69,57.18)]、冬季低波动[0.41(0.16,0.94)、16.69(12.28,31.92)],两者比较差异有统计意义(χ^(2)=3.10、2.98,P<0.05);肝癌IL-1β呈春季表达低谷,与秋、冬季节比较差异有统计学意义(χ^(2)=-3.69、-3.20,P<0.05),胃癌IL-6、IL-13、IL-1β在秋季表达下调,与春、夏、冬季节比较差异有统计学意义(χ^(2)=3.64、3.05、-4.36,3.91、2.02、-2.16,4.37、2.10、-4.89,P<0.05)。结论常见恶性肿瘤外周血细胞因子谱受肿瘤类型、年龄、性别及季节因素影响。细胞因子波动可能反映免疫状态,已有证据表明细胞因子与肿瘤免疫治疗疗效及不良反应有关,如何结合这些细胞因子特征优化肿瘤免疫治疗值得未来进一步研究。
Objective To investigate the expression heterogeneity of 12 cytokines(IL-1β、IL-1Ra、IL-4、IL-6、IL-13、IL-17、Eotaxin、IP-10、MCP-1、RANTES、G-CSF、PDGF-BB)in peripheral blood across tumor types,age groups,genders,and seasons,thereby systematically characterizing systemic immune status and providing novel insights for cancer immunotherapy.Methods This retrospective study enrolled 1,842 malignancy patients admitted to PLA General Hospital from March 2016 to July 2023,with peripheral blood cytokine profiling.The tumor types of the enrolled patients included lung cancer,liver cancer,gastric cancer,breast cancer,colorectal cancer,pancreatic cancer,ovarian cancer and esophageal cancer.There were 1,266 male patients and 576 female patients;their ages ranged from 25 to 92 years old.The seasons were divided into spring(March to May),summer(June to August),autumn(September to November),and winter(December to February).Comparative analyses evaluated cytokine expression variations across tumor types and their correlations with age,gender,and seasonal factors.Results The expressions of nine cytokines,IL-1Ra,IL-13,IL-17,Eotaxin,G-CSF,IP-10,MCP-1,PDGF-BB and RANTES,were statistically significant in the eight tumors(χ^(2)=36.17,21.75,40.02,32.19,28.67,19.08,48.75,26.62,21.37,P<0.001).Among them,IL-1Ra was significantly underexpressed in pancreatic cancer;IL-13 is more elevated in colorectal cancer than in liver cancer;IL-17 is highly expressed in ovarian cancer and low in esophageal cancer;RANTES is highly expressed in lung cancer;MCP-1 is highly expressed in esophageal cancer;Eotaxin was highly expressed in ovarian cancer and low in lung cancer;The concentration of IP-10 in lung cancer was significantly higher than that in colorectal cancer;PDGF-BB is underexpressed in pancreatic cancer;G-CSF is upregulated in esophageal cancer and downregulated in pancreatic cancer.However,there was no significant difference in the expression of three cytokines,IL-1β,IL-4 and IL-6,in 8 tumors(P>0.05).The expression of cytokines was also correlated with age,and IL-4 was positively correlated with age in breast cancer(r=0.306,P<0.001).IP-10 was weakly positively correlated with age in lung cancer and colorectal cancer(r=0.127、0.294,P<0.001).Eotaxin increased with age in lung,liver,breast and colorectal cancers(r=0.102,0.301,0.506,0.265,P<0.05).PDGF-BB was age-dependently down-regulated in liver,gastric,breast and colorectal cancers(r=-0.284,-0.168,-0.316,-0.308,P<0.001).The gender differences of cytokines showed that Eotaxin in male lung cancer,PDGF-BB in liver cancer,and G-CSF in gastric cancer were significantly higher than those in female(Z=-2.29,-3.98,-2.71,P<0.05).IL-4,IL-17,Eotaxin,IP-10 in female hepatocellular carcinoma and RANTES in gastric cancer were significantly higher than those in male(Z=-2.9,-3.63,-3.39,-2.94,-2.71,P<0.05).The seasonal characteristics of cytokines showed that the levels of IL-1βand IL-17 in lung cancer fluctuated high in summer[0.60(0.16,1.77)、20.29(13.69,57.18)]and low in winter[0.41(0.16,0.94)、16.69(12.28,31.92)],and the difference between the two was statistically significant(χ^(2)=3.10,2.98,P<0.05).The expression of IL-1βin liver cancer was at a trough in spring,which was statistically significant compared with that in autumn and winter(χ^(2)=-3.69,-3.20,P<0.05),and the expression of IL-6,IL-13 and IL-1βin gastric cancer was down-regulated in autumn,which was statistically significant compared with that in spring,summer and winter(χ^(2)=3.64,3.05,-4.36,3.91,2.02,-2.16,4.37,2.10,-4.89,P<0.05).Conclusion The peripheral blood cytokine profile in common malignancies is affected by tumor type,age,gender,and season,with fluctuations likely related to immune status.Existing evidence links cytokine changes to tumor immunotherapy efficacy and adverse reactions.Thus,optimizing cancer immunotherapy by incorporating these immune-related cytokine changes warrants further investigation.
作者
何唱
孙胜杰
赵晓
李珂
杨子仲
焦顺昌
He Chang;Sun Shengjie;Zhao Xiao;Li Ke;Yang Zizhong;Jiao Shunchang(Chinese PLA Medical School,Beijing 100853,China)
出处
《中华保健医学杂志》
2025年第4期644-649,共6页
Chinese Journal of Health Care and Medicine
基金
国家重点研发计划(2016YFC0905402)。
