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摘要:
目的 研究血清总胆红素（total bilirubin，TBIL）与非小细胞肺癌（non-small cell lung cancer，NSCLC）患者临床病理特征以及炎症细胞之间的关系，探讨血清TBIL对NSCLC患者治疗的指导意义以及预后价值。 方法 回顾性分析2017年3月至2020年12月于上海中医药大学附属市中医医院就诊的NSCLC患者332例，收集患者临床资料，并通过电话、门诊复诊等方式进行随访，采用Logistic回归分析进行单因素分析，采用Kaplan-Meier生存曲线进行生存分析。 结果 NSCLC患者血清TBIL水平在不同性别中存在差异，男性高于女性（P<0.05），但在不同年龄、有无吸烟史及患病时间中无显著性差异（P>0.05）；在不同淋巴浸润程度、是否存在远处转移和不同肿瘤分期中，血清TBIL表达存在显著性差异（P<0.05）。Logistic回归分析发现TBIL、白蛋白、谷草转氨酶水平与患者预后具有显著相关性（P<0.05）；当女性患者TBIL>9.85 μmol/L时，患者无病生存期相比TBIL≤9.85 μmol/L时延长，男性患者TBIL水平与无病生存期无明显相关性（P>0.05）。根据TBIL水平将患者分为高水平和低水平组，男性患者淋巴细胞比例在TBIL高水平组较高，中性粒细胞淋巴细胞比值（neutrophil- lymphocyte ratio，NLR）在高水平组较低；女性患者淋巴细胞比例在高水平组较高，NLR、CD3、CD4细胞比例在高水平组较低（P<0.05）。 结论 血清TBIL在NSCLC早期患者中的表达水平高于进展期患者，有望成为NSCLC的治疗指导依据；TBIL与中性粒细胞和NLR之间可能存在协同作用，共同在肺癌免疫调节中发挥抗肿瘤作用。 Abstract:Objective To investigate the relationship between serum total bilirubin (TBIL) and the clinicopathological characteristics and inflammatory cells of non-small cell lung cancer (NSCLC) patients, and to explore the significance of serum TBIL in guiding the treatment of NSCLC patients and its prognostic value. Methods A retrospective analysis of 332 patients with NSCLC who attended Municipal Hospital of Traditional Chinese Medicine Affiliated to Shanghai University of Traditional Chinese Medicine from March 2017 to December 2020, with clinical data collected and followed up by telephone and outpatient follow-up, was performed using Logistic regression analysis for univariate analysis and Kaplan-Meier survival curve for survival analysis. Results The serum TBIL levels of NSCLC patients differed in genders, with males being higher than females (P<0.05), but there were no significant differences among ages, smoking and the duration of disease (P>0.05); in addition, serum TBIL was differentially expressed by degree of lymphatic infiltration, whether or not distant metastasis was present, and TNM stage (P<0.05). Logistic regression analysis showed that TBIL, albumin and glutamate aminotransferase levels had a significant effect on prognosis of the disease (P<0.05); female patients had a better prognosis when their TBIL levels were greater than 9.85 μmol/L when compared with those with TBIL ≤9.85 μmol/L, but there was no correlation between TBIL levels and disease-free survival in male patients (P>0.05). Patients were assigned into high or low level groups according to TBIL levels. The percentage of lymphocytes in male patients was highly expressed in the high level group and neutrophil-lymphocyte ratio (NLR) values were low in the high level group; The percentage of lymphocytes in female patients was highly expressed in the high level group, but the NLR values and CD3, CD4 cell proportions were low in the high level group (P<0.05). Conclusions The expression level of serum TBIL was higher in NSCLC patients with early-stage than in patients with progressive stage, which is expected to be a basis for guiding the treatment of NSCLC; there may be synergistic effect between TBIL and neutrophils and NLR, which together play an anti-tumor role in immune regulation of lung cancer. -
Key words:
- non-small cell lung cancer (NSCLC) /
- bilirubin /
- oxidative stress /
- tumor immunity
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表 1 血清总胆红素水平与肺癌临床病例特征的关系
项目 n（%） 血清TBIL（μmol/L） Z P 性别 −2.375 0.018 男 133（40.1） 13.1（10.9，15.5） 女 199（59.9） 12.3（10.1，14.8） 年龄（岁） −1.273 0.203 ≤63 173（52.1） 12.4（10.1，15） >63 159（47.9） 12.8（10.95，14.8） 吸烟史 −1.472 0.141 有 77（76.8） 13.2（10.8，15） 无 255（23.2） 12.4（10.25，14.9） 肿瘤直径（cm） −0.440 0.660 ≤2 200（60.2） 12.7（10.4，15.5） >2 101（30.4） 12.6（10.4，14.5） 未知 31（9.4） 12.1（9.6，15.0） 淋巴结浸润 −2.357 0.018 无 268（80.7） 12.8（10.45，15.5） 有 64（19.3） 11.8（9.35，13.75） 远处转移 −2.053 0.040 无 290（87.3） 12.75（10.4，15.5） 有 42（12.7） 11.6（8.9，13.7） 分期 −2.779 0.005 Ⅰ～Ⅱ期 272（81.9） 13.77±0.32 Ⅲ～Ⅳ期 60（18.1） 11.66±0.50 患病时间（年） −1.387 0.165 ≤2 206（62.0） 12.3（10，15） >2 126（38.0） 12.9（11，14.8） 
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表 2 二元Logitic回归分析肿瘤分期病情程度的影响因素
项目 B P OR 95%置信区间 性别 −0.662 0.125 0.516 0.222~1.201 年龄 0.026 0.212 1.026 0.985~1.068 患病时间（年） <0.010 0.822 1.000 1.000~1.000 TBIL −0.127 0.012 0.881 0.798~0.973 总蛋白 0.004 0.078 1.004 1.000~1.000 白蛋白 −0.241 <0.010 0.786 0.687~0.899 球蛋白 0.020 0.563 1.029 0.933~1.135 谷草转氨酶 0.091 0.004 1.095 1.029~1.165 谷丙转氨酶 −0.047 0.027 0.954 0.915~0.995 γ−谷氨酰转肽酶 0.003 0.730 1.003 0.984~1.023 前白蛋白 0.001 0.717 1.001 0.995~1.007 总胆固醇 −0.229 0.233 0.798 0.545~1.159 甘油三酯 0.193 0.257 1.213 0.869~1.694 尿素氮 −0.411 0.024 0.663 0.464~0.947 血肌酐 0.026 0.052 1.027 1.000~1.055 尿酸 0.002 0.083 1.002 1.000~1.005
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表 3 男性患者不同TBIL水平炎症细胞表达情况
男性 低水平组 高水平组 Z/F P WBC 7.36（3.13,74.50） 6.00（3.05,12.43） −1.16 0.25 中性粒细胞（%） 58.76±1.35 57.17±1.65 2.03 0.16 淋巴细胞（%） 27.85（2.84,74.70） 31.60（8.40,55.80） −2.58 0.01 NLR 2.35（0.54,20.71） 1.76（0.55,8.67） −3.19 <0.01 CD3（%） 60.83±1.48 63.93±1.88 1.62 0.21 CD4（%） 33.31±1.06 34.46±1.45 0.78 0.38 CD8（%） 22.76（7.52,44.10） 23.54（10.49,58.83） −0.32 0.75
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表 4 女性患者不同TBIL水平炎症细胞表达情况
女性 低水平组 高水平组 Z/F P WBC 5.98（3.65,10.27） 5.77（1.17,9.80） −0.57 0.57 中性粒细胞（%） 57.40±1.66 56.70±0.72 0.56 0.46 淋巴细胞（%） 30.03±1.59 32.85±0.71 2.73 0.10 NLR 1.93（0.79,6.58） 1.64（0.65,8.24） −2.20 0.03 CD3（%） 69.69（22.98,79.52） 64.91（40.36,85.81） −2.53 0.01 CD4（%） 38.06±1.40 35.14±0.65 1.37 0.04 CD8（%） 24.76±1.38 23.66±0.67 1.98 0.16
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