胃肠道肿瘤患者免疫炎症指标与病理特征的关系研究

Relationship between immune and inflammatory markers and clinicopathological characteristics in patients with gastrointestinal cancers

目的分析胃肠道肿瘤患者围手术期免疫和炎症标志物变化并探讨其与病理特征间的关系。方法收集从2022年6月至2023年9月就诊于华中科技大学同济医学院附属同济医院的15例胃肠道肿瘤患者围手术期数据,其中胃癌2例,结直肠癌13例,于术前1 d及术后第3天分别采集外周血行免疫炎症全套分析,检测总B淋巴细胞、NK细胞、总T淋巴细胞及多个T淋巴细胞亚型,同时检测白介素2、4、6及肿瘤坏死因子。使用非参数配对t检验分析手术前后免疫炎症指标变化有无统计学意义;多组间比较采用单因素方差分析(One-way ANOVA)。结果手术后Th+Ts细胞计数[(613.85±224.98)个/μl]、总T淋巴细胞计数[(639.44±222.85)个/μl]、抑制/细胞毒性T淋巴细胞计数[(230.70±109.73)个/μl]、NK细胞计数[(96.03±73.90)个/μl]、T淋巴细胞+B淋巴细胞+NK细胞计数[(815.54±300.08)个/μl]均低于术前[(783.67±222.26)、(822.27±217.10)、(322.21±153.46)、(171.06±100.73)、(1103.67±310.95)个/μl,t=3.04、3.24、3.05、3.95、4.06,P<0.01]。进一步分析显示,肿瘤低、中、高分化程度与术前NK细胞计数[(97.38±32.08)、(223.60±96.85)、(66.68)个/μl]、表达第二信号受体Th淋巴细胞[(96.84±2.25)、(91.78±8.77)、(67.96)个/μl]、活化Ts细胞[(62.67±10.69)、(59.90±11.68)、21.26个/μl]明显相关(F=4.77、6.56、5.78,P<0.05);肿瘤分级(T1、T2、T3、T4)与术前总B淋巴细胞[9.48%、(5.56±1.73)%、(8.37±3.65)%、(17.15±4.17)%]、NK细胞[8.07%、(22.14±7.30)%、(16.53±5.60)%、(7.16±1.84)%]、表达第二信号受体Th淋巴细胞[67.96、(90.01±12.97)、(94.05±6.79)、(95.95±1.15)个/μl]、活化Ts细胞[21.26、(60.66±8.73)、(63.92±11.74)、(53.06±9.92)个/μl]明显相关(F=6.36、4.45、3.71、4.81,P<0.01);术后有淋巴结转移时术前IL-2[(2.10±0.65)pg/ml]、IL-4[(2.01±0.84)pg/ml]及IL-10[(3.02±1.26)pg/ml]均低于无淋巴结转移时各指标水平[(2.82±0.38)、(2.76±0.45)、(4.24±0.63)pg/ml,t=2.63、2.21、2.32,P<0.05];有淋巴结外种植转移(ENTD)时,术前TNF-γ水平[(3.12±0.35)pg/ml]高于无ENTD时[(2.04±0.49)pg/ml,t=2.93,P<0.05];有神经侵犯时IL-2[(2.14±0.70)pg/ml]及IL-4[(2.01±0.88)pg/ml]低于无神经侵犯时[(2.79±0.37)、(2.76±0.37)pg/ml,t=2.28、2.18,P<0.05]。结论胃肠道肿瘤患者围手术期免疫炎症指标存在变化,揭示免疫炎症指标与临床病理特征间潜在的关系。

Objective To analyze the changes in immune and inflammatory markers during the perioperative period of gastrointestinal cancer patients and further evaluate the relationship between preoperative immune and inflammatory markers and patients’clinicopathological characteristics.Methods 15 gastrointestinal cancer patients enrolled from June 2022 to September 2023 who underwent surgery in Tongji Hospital of Huazhong University of Science and Technology were collected,including 2 cases of gastric cancer and 13 cases of colorectal cancer.Analysis of peripheral blood immune and inflammatory markers was conducted one day before surgery and on the 3rd day post-surgery,including total B lymphocytes,Natural Killer(NK)cells,total T lymphocytes and various T cell subtypes,inflammatory markers such as interleukin(IL)-2,4,6 and tumor necrosis factors(TNF).Non-parametric paired t-tests were used to analyze the statistical significance of changes in immune and inflammatory markers before and after surgery.One-way ANOVA was employed for comparisons among multiple groups.Results After surgery,Post-operatively,the counts of Th+Ts cells[(613.85±224.98)cells/μl],total T lymphocytes[(639.44±222.85)cells/μl],suppressive/cytotoxic T lymphocytes[(230.70±109.73)cells/μl],NK cells[(96.03±73.90)cells/μl],and the combined count of T lymphocytes+B lymphocytes+NK cells[(815.54±300.08)cells/μl]were all lower than pre-operative levels(783.67±222.26),(822.27±217.10),(322.21±153.46),(171.06±100.73),and[(1103.67±310.95)cells/μl]respectively(t=3.04,3.24,3.05,3.95,4.06,P<0.01).Further analysis revealed significant correlations between tumor differentiation grades(low,moderate,high)and pre-operative counts of NK cells[(97.38±32.08),(223.60±96.85),66.68 cells/μl],expression of second signal receptor Th lymphocytes[(96.84±2.25),(91.78±8.77),67.96 cells/μl],and activation of Ts cells[(62.67±10.69),(59.90±11.68),21.26 cells/μl,F=4.77,6.56,5.78,P<0.05].Tumor staging(T1,T2,T3,T4)was significantly correlated with pre-operative total B lymphocytes[9.48%,(5.56±1.73)%,(8.37±3.65)%,(17.15±4.17)%],NK cells[8.07%,(22.14±7.30)%,(16.53±5.60)%,(7.16±1.84)%],expression of second signal receptor Th lymphocytes[67.96,(90.01±12.97),(94.05±6.79),(95.95±1.15)cells/μl],and activation of Ts cells[21.26,(60.66±8.73),(63.92±11.74),(53.06±9.92)cells/μl,F=6.36,4.45,3.71,4.81,P<0.01].In cases of post-operative lymph node metastasis,pre-operative levels of IL-2[(2.10±0.65)pg/ml],IL-4[(2.01±0.84)pg/ml],and IL-10[(3.02±1.26)pg/ml]were lower compared to levels without lymph node metastasis[(2.82±0.38),(2.76±0.45),(4.24±0.63)pg/ml]respectively(t=2.63,2.21,2.32,P<0.05).In cases of ENTD,pre-operative tumor necrosis factor(TNF)-γlevels[(3.12±0.35)pg/ml]were higher compared to cases without ENTD[(2.04±0.49)pg/ml,t=2.93,P<0.05].In cases of neural invasion,pre-operative IL-2[(2.14±0.70)pg/ml]and IL-4[(2.01±0.88)pg/ml]were lower compared to cases without neural invasion[(2.79±0.37),(2.76±0.37)pg/ml]respectively(t=2.28,2.18,P<0.05).Conclusion This small-sample study explored the changes in immune and inflammatory markers during the perioperative period of gastrointestinal cancer patients and their relationship with clinicopathological characteristics.