切换至 "中华医学电子期刊资源库"

中华肺部疾病杂志(电子版) ›› 2021, Vol. 14 ›› Issue (03) : 283 -287. doi: 10.3877/cma.j.issn.1674-6902.2021.03.004

论著

血细胞因子在肺癌分型及预后中的临床意义
许琼1, 马硝惟2, 刘斌1, 蒋捍东1, 吴学玲1,()   
  1. 1. 201112 上海,上海交通大学医学院附属仁济医院呼吸科
    2. 201112 上海,上海交通大学医学院附属仁济医院检验科
  • 收稿日期:2021-01-15 出版日期:2021-06-25
  • 通信作者: 吴学玲
  • 基金资助:
    上海交大医学院附属仁济医院临床创新课题(2019NYLYCP0103)

Role of peripheral cytokines in lung cancer pathological typing and prognosis

Qiong Xu1, Xiaowei Ma2, Bin Liu1, Handong Jiang1, Xueling Wu1,()   

  1. 1. Department of Respiratory, Shanghai Jiaotong University School of Medicine, Renji Hospital, Shanghai 201112, China
    2. Clinical laboratory, Shanghai Jiaotong University School of Medicine, Renji Hospital, Shanghai 201112, China
  • Received:2021-01-15 Published:2021-06-25
  • Corresponding author: Xueling Wu
引用本文:

许琼, 马硝惟, 刘斌, 蒋捍东, 吴学玲. 血细胞因子在肺癌分型及预后中的临床意义[J]. 中华肺部疾病杂志(电子版), 2021, 14(03): 283-287.

Qiong Xu, Xiaowei Ma, Bin Liu, Handong Jiang, Xueling Wu. Role of peripheral cytokines in lung cancer pathological typing and prognosis[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2021, 14(03): 283-287.

目的

探讨细胞因子在肺癌不同病理类型和预后判断中的意义。

方法

收集就诊于上海交通大学附属仁济医院的127例肺癌患者以及11例支气管哮喘、68例社区获得性肺炎患者的临床数据,包括病理类型、生存时间、临床分期、年龄等,同时收集这些患者多次入院病程中外周血细胞因子和肺癌相关肿瘤指标的实验室检查资料。统计分析细胞因子在肺癌、支气管哮喘和社区获得性肺炎中的表达差异。筛选出肺癌患者中升高的细胞因子,并统计分析它与肺癌分期、病理类型及预后的相关性。

结果

IL-6在肺癌患者中的水平明显高于支气管哮喘和社区获得性肺炎组(P<0.001),而其它的细胞因子在这三种疾病中的表达无明显差异。IL-6在肺鳞癌患者中升高最为明显;IL-6水平的高低与临床TNM分期相关,在Ⅲ、Ⅳ期肺癌患者中最高(P<0.05)。在肺癌的死亡患者中,血IL-6的水平随疾病的进展逐步升高,相关回归分析具有统计学差异(P<0.01)。生存分析显示IL-6高水平组的生存时间短于IL-6低水平组,风险比为3.04(P<0.05)。

结论

IL-6与肺癌患者病情进展及预后相关。

Objective

To investigate the effectiveness of cytokines as pathological and prognostic markers for lung cancer.

Methods

Peripheral levels of cytokines and lung cancer related tumor markers during multiple hospitalization, as well as clinical data, including pathological type, survival time, clinical stage and age, were collected in a retrospective cohort with 127 lung cancer patients, 11 asthma and 68 pneumonia patients. All patients were admitted to Renji hospital, Shanghai Jiao Tong University School of Medicine. To identify new markers for lung cancer diagnostics, levels of cytokines were compared between lung cancer, asthma and pneumonia patients with statistical tests. The dynamics of significant cytokines were further evaluated among disease stages and during disease progression.

Results

The cytokine IL-6 levels were significantly higher in lung cancer compared to that in asthma and pneumonia patients (P<0.001). However, the level of other cytokines were not statistically different among these three groups. Furthur analysis showed that IL-6 levels were related to pathological type with highest level in squamous lung cancer. IL-6 levels were also associated with TNM stage, and were higher in Ⅲ-Ⅳ stages (P<0.05). It was significantly increased with disease progression in patients who died of lung cancer (P<0.01). For individuals with high levels of IL-6, poorer overall survival was observed compared to those with lower levels of this cytokine (hazard ratio=3.04, P<0.05).

Conclusion

Peripheral IL-6 level is an effective marker for lung cancer progression and prognostic analysis.

图1 细胞因子及肿瘤标志物在不同疾病中的表达
表1 外周血细胞因子的筛选
图2 IL-6与肺癌病理类型、临床分期的关系
图3 IL-6水平与病程进展的关系
1
钱桂生. 肺癌不同病理类型发病率的变化情况及其原因[J/CD]. 中华肺部疾病杂志(电子版), 2011, 4(1): 1-5.
2
WHO. Available online at: accessed April, 2021.

URL    
3
Jiang ZF, Wang M, Xu JL. Thymidine kinase 1 combined with CEA, CYFRA21-1 and NSE improved its diagnostic value for lung cancer[J]. Life Sci, 2018, 194: 1-6.
4
Zimmerman R, Wahren B, Edsmyr F. Assessment of serial CEA determinations in urine of patients with bladder carcinoma[J]. Cancer, 1980, 46(8): 1802-1809.
5
Zhao M, Liu Y, Liu R, et al. Upregulation of IL-11, an IL-6 family cytokine, promotes tumor progression and correlates with poor prognosis in non-small cell lung cancer[J]. Cell Physiol Biochem, 2018, 45(6): 2213-2224.
6
Smyth MJ, Cretney E, Kershaw MH, et al. Cytokines in cancer immunity and immunotherapy[J]. Immunol Rev, 2004, 202: 275-293.
7
Tang H, Bai Y, Shen W, et al. Clinical significance of combined detection of interleukin-6 and tumour markers in lung cancer[J]. Autoimmunity, 2018, 51(4): 191-198.
8
Naqash AR, Yang LV, Sanderlin EJ, et al. Interleukin-6 as one of the potential mediators of immune-related adverse events in non-small cell lung cancer patients treated with immune checkpoint blockade: evidence from a case report[J]. Acta Oncol, 2018, 57(5): 705-708.
9
Pinargote-Celorio H, Miralles G, Cano M, et al. Cytokine levels predict 30-day mortality in octogenarians and nonagenarians with community-acquired pneumonia: a retrospective observational study[J]. Eur J Clin Microbiol Infect Dis, 2020, 39(2): 299-307.
10
Mendez R, Menendez R, Cilloniz C, et al. Initial inflammatory profile in community-acquired pneumonia depends on time since onset of symptoms[J]. Am J Respir Crit Care Med, 2018, 198(3): 370-378.
11
Bazan-Socha S, Mastalerz L, Cybulska A, et al. Prothrombotic state in asthma is related to increased levels of inflammatory cytokines, IL-6 and TNFalpha, in peripheral blood[J]. Inflammation, 2017, 40(4): 1225-1235.
12
Kumari N, Dwarakanath BS, Das A, et al. Role of interleukin-6 in cancer progression and therapeutic resistance[J]. Tumour Biol, 2016, 37(9): 11553-11572.
13
Chu Y, Wang Y, Peng W, et al. STAT3 activation by IL-6 from adipose-derived stem cells promotes endometrial carcinoma proliferation and metastasis[J]. Biochem Biophys Res Commun, 2018, 500(3): 626-631.
14
Knupfer H, Preiss R. Significance of interleukin-6 (IL-6) in breast cancer (review)[J]. Breast Cancer Res Treat, 2007, 102(2): 129-135.
15
Lin Y, He Z, Ye J, et al. Progress in understanding the IL-6/STAT3 Pathway in Colorectal Cancer[J]. Onco Targets Ther, 2020, 13: 13023-13032.
16
Kucera R, Topolcan O, Treskova I, et al. Evaluation of IL-2, IL-6, IL-8 and IL-10 in malignant melanoma diagnostics[J]. Anticancer Res, 2015, 35(6): 3537-3541.
17
Pan YW, Zhou ZG, Wang M, et al. Combination of IL-6, IL-10, and MCP-1 with traditional serum tumor markers in lung cancer diagnosis and prognosis[J]. Genet Mol Res, 2016, 15(4). doi: 10.4238/gmr15048949.
18
Chang CH, Hsiao CF, Yeh YM, et al. Circulating interleukin-6 level is a prognostic marker for survival in advanced nonsmall cell lung cancer patients treated with chemotherapy[J]. Int J Cancer, 2013, 132(9): 1977-1985.
19
Huang X, Xiao S, Zhu X, et al. miR-196b-5p-mediated downregulation of FAS promotes NSCLC progression by activating IL-6-STAT3 signaling[J]. Cell Death Dis, 2020, 11(9): 785.
20
Hong DS, Angelo LS, Kurzrock R. Interleukin-6 and its receptor in cancer: implications for translational therapeutics[J]. Cancer, 2007, 110(9): 1911-1928.
21
Lederle W, Depner S, Schnur S, et al. IL-6 promotes malignant growth of skin SCCs by regulating a network of autocrine and paracrine cytokines[J]. Int J Cancer, 2011, 128(12): 2803-2814.
22
Fisher DT, Appenheimer MM, Evans SS. The two faces of IL-6 in the tumor microenvironment [J]. Semin Immunol, 2014, 26(1): 38-47.
23
Loeb LA, Ernster VL, Warner KE, et al. Smoking and lung cancer: an overview[J]. Cancer Res, 1984, 44(12 Pt 1): 5940-5958.
24
Hackshaw AK, Law MR, Wald NJ. The accumulated evidence on lung cancer and environmental tobacco smoke[J]. BMJ, 1997, 315(7114): 980-988.
25
Chen PH, Chang H, Chang JT, et al. Aryl hydrocarbon receptor in association with RelA modulates IL-6 expression in non-smoking lung cancer[J]. Oncogene, 2012, 31(20): 2555-2565.
26
Koo JB, Han JS. Cigarette smoke extract-induced interleukin-6 expression is regulated by phospholipase D1 in human bronchial epithelial cells[J]. J Toxicol Sci, 2016, 41(1): 77-89.
27
Xie C, Zhu J, Jiang Y, et al. Sulforaphane inhibits the acquisition of tobacco smoke-induced lung cancer stem cell-like properties via the IL-6/DeltaNp63alpha/Notch Axis[J]. Theranostics, 2019, 9(16): 4827-4840.
28
Gandhi L, Rodriguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer[J]. N Engl J Med, 2018, 378(22): 2078-2092.
29
Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial[J]. Lancet, 2019, 394(10212): 1929-1939.
30
Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer[J]. N Engl J Med, 2015, 372(21): 2018-2028.
[1] 马中正, 杨云川, 马翔, 周迟, 丁丁, 霍俊一, 徐楠, 崔培元, 周磊. 胰腺癌双硫死亡相关的lncRNA预后模型的构建及免疫反应研究[J]. 中华普通外科学文献(电子版), 2024, 18(05): 368-376.
[2] 屈翔宇, 张懿刚, 李浩令, 邱天, 谈燚. USP24及其共表达肿瘤代谢基因在肝细胞癌中的诊断和预后预测作用[J]. 中华普外科手术学杂志(电子版), 2024, 18(06): 659-662.
[3] 顾雯, 凌守鑫, 唐海利, 甘雪梅. 两种不同手术入路在甲状腺乳头状癌患者开放性根治性术中的应用比较[J]. 中华普外科手术学杂志(电子版), 2024, 18(06): 687-690.
[4] 付成旺, 杨大刚, 王榕, 李福堂. 营养与炎症指标在可切除胰腺癌中的研究进展[J]. 中华普外科手术学杂志(电子版), 2024, 18(06): 704-708.
[5] 梁孟杰, 朱欢欢, 王行舟, 江航, 艾世超, 孙锋, 宋鹏, 王萌, 刘颂, 夏雪峰, 杜峻峰, 傅双, 陆晓峰, 沈晓菲, 管文贤. 联合免疫治疗的胃癌转化治疗患者预后及术后并发症分析[J]. 中华普外科手术学杂志(电子版), 2024, 18(06): 619-623.
[6] 张志兆, 王睿, 郜苹苹, 王成方, 王成, 齐晓伟. DNMT3B与乳腺癌预后的关系及其生物学机制[J]. 中华普外科手术学杂志(电子版), 2024, 18(06): 624-629.
[7] 孙建娜, 孔令军, 任崇禧, 穆坤, 王晓蕊. 266例首诊Ⅳ期乳腺癌手术患者预后分析[J]. 中华普外科手术学杂志(电子版), 2024, 18(05): 502-505.
[8] 袁庆港, 刘理想, 张亮, 周世振, 高波, 丁超, 管文贤. 尿素-肌酐比值(UCR)可预测结直肠癌患者术后的长期预后[J]. 中华普外科手术学杂志(电子版), 2024, 18(05): 506-509.
[9] 黄福, 王黔, 金相任, 唐云川. VEGFR2、miR-27a-5p在胃癌组织中的表达与临床病理参数及预后的关系研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(05): 558-561.
[10] 肖丹, 陈辰, 查晔军, 公茂琪, 花克涵, 孙伟桐, 蒋协远. 改良松解术治疗创伤后肘关节僵硬的疗效及危险因素分析[J]. 中华老年骨科与康复电子杂志, 2024, 10(05): 257-263.
[11] 唐诗, 薛传优, 叶兴, 张鸿举, 戴瑞. 急性病毒性肝炎患者血脂、血糖、蛋白、尿酸变化特点及其与预后的关联[J]. 中华消化病与影像杂志(电子版), 2024, 14(05): 396-399.
[12] 李素娟, 王文玲, 董洪敏, 李小凯, 黄思成, 王刚. 多原发与单原发大肠腺癌的预后分析[J]. 中华消化病与影像杂志(电子版), 2024, 14(05): 407-412.
[13] 孙文恺, 沈青, 杭丽, 张迎春. 纤维蛋白原与清蛋白比值、中性粒细胞与白蛋白比值、C反应蛋白与溃疡性结肠炎病情评估和预后的关系[J]. 中华消化病与影像杂志(电子版), 2024, 14(05): 426-431.
[14] 郭曌蓉, 王歆光, 刘毅强, 何英剑, 王立泽, 杨飏, 汪星, 曹威, 谷重山, 范铁, 李金锋, 范照青. 不同亚型乳腺叶状肿瘤的临床病理特征及预后危险因素分析[J]. 中华临床医师杂志(电子版), 2024, 18(06): 524-532.
[15] 闫战涛, 王辉, 周梓迪, 史勇强, 陈铜兵. 胃淋巴上皮瘤样癌三级淋巴结构特征及其与预后的相关性[J]. 中华临床医师杂志(电子版), 2024, 18(05): 455-461.
阅读次数
全文


摘要