WU Li'na, GAO Yi, LI Wosong, LIU Yong, QIN Xiaosong. Application Value of Serum Kreb Von Den Lungen-6 in the Adjuvant Treatment of Lung Injury after Non-small Cell Lung Cancer Surgery[J]. Medical Journal of Peking Union Medical College Hospital, 2021, 12(4): 496-502. DOI: 10.12290/xhyxzz.2021-0308
Citation: WU Li'na, GAO Yi, LI Wosong, LIU Yong, QIN Xiaosong. Application Value of Serum Kreb Von Den Lungen-6 in the Adjuvant Treatment of Lung Injury after Non-small Cell Lung Cancer Surgery[J]. Medical Journal of Peking Union Medical College Hospital, 2021, 12(4): 496-502. DOI: 10.12290/xhyxzz.2021-0308

Application Value of Serum Kreb Von Den Lungen-6 in the Adjuvant Treatment of Lung Injury after Non-small Cell Lung Cancer Surgery

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Science and Technology of National Health Commission 2021KYSHX00601

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  • Corresponding author:

    QIN Xiaosong  Tel: 86-24-96615-72128, E-mail: qinxs@sj-hospital.org

  • Received Date: April 05, 2021
  • Accepted Date: June 07, 2021
  • Issue Publish Date: July 29, 2021
  •   Objective  To investigate the diagnostic value of serum kreb von den lungen-6 (KL-6) in lung injury from postoperative adjuvant treatment in non-small cell lung cancer (NSCLC).
      Methods  This study is a retrospective analysis including NSCLC with postoperative adjuvant treatment and NSCLC with merely surgical treatment patients diagnosed and treated in Shengjing Hospital of China Medical University from November 2017 to July 2020. Consensus on the diagnosis of drug induced lung injury and radiation induced lung injury was used as the diagnostic criteria for lung injury from postoperative adjuvant treatment. NSCLC patients with postoperative adjuvant treatment were divided into the lung-injury group and the non lung-injury group. those only with surgery were as NSCLC-surgery group. Match the healthy adults of the physical examination center at the same period as the healthy control group based on the age and gender. Fasting venous blood was collected from NSCLC patients and healthy adults for detection of serum KL-6. The time of venous blood collection was on the day of lung-injury diagnosis for the lung-injury group, after 3 to 4 months of adjuvant treatment for the non lung-injury group, before and 7 to 10 days after surgery for NSCLC-surgery group, and on the day of physical examination for the healthy control group. The levels of serum KL-6 in each group were compared, and the non lung-injury group was used as the control, the diagnostic threshold value of serum KL-6 for adjuvant therapeutic lung injury was preliminarily established based on the receiver operating characteristic(ROC) curve.
      Results  A total of 206 NSCLC patients who met the selection and exclusion criteria were enrolled, of which 51 cases were in lung-injury group, 52 cases were in non lung-injury group, and 103 cases were in NSCLC-surgery group. Meanwhile, 103 cases in healthy control group were enrolled. There was no significant difference among the basic clinical data of the four groups. The levels of serum KL-6 in the descending order were lung-injury group [512.40 (322.30, 819.20)kU/L], pre-operation of the NSCLC-surgery group [204.40 (162.70, 283.20)kU/L], healthy control group [177.70 (154.20, 206.40)kU/L], non lung-injury group [147.80 (114.25, 229.80)kU/L], and post-operation of the NSCLC-surgery group [143.80 (111.90, 247.80)kU/L]. There was no significant difference in serum KL-6 between the non lung-injury group and post-operation of the NSCLC-surgery group (P=0.879), while the difference between other groups were statistically significant (all P < 0.05). The ROC curve analysis showed that the area under the curve (AUC) of serum KL-6 for the diagnosis of lung injury from NSCLC postoperative adjuvant treatment was 0.972 (95% CI: 0.948-0.997), and the diagnostic sensitivity, specificity, the positive and negative likelihood ratio were 86.3% (95% CI: 73.0%-94.1%), 96.2% (95% CI: 86.2%-98.7%), 22.43 (95% CI: 5.74-87.69), 0.14 (95% CI: 0.07-0.28), respectively. The best diagnostic cut-off value was 310.15 kU/L.
      Conclusions  Serum KL-6 is significantly increased in the patients with lung injury from NSCLC postoperative adjuvant treatment, and it has high application value in the diagnosis of lung injury from postoperative adjuvant treatment in NSCLC, but it still needs further verification by prospective studies with large samples.
  • [1]
    Zeng H, Chen W, Zheng R, et al. Changing cancer survival in China during 2003-15: a pooled analysis of 17 population-based cancer registries[J]. Lancet Glob Health, 2018, 6: e555-e567. DOI: 10.1016/S2214-109X(18)30127-X
    [2]
    孙建国, 李梦侠, 杨镇洲. PD-L1高表达晚期非小细胞肺癌一线免疫治疗策略的探讨[J]. 第三军医大学学报, 2020, 42: 314-319. https://www.cnki.com.cn/Article/CJFDTOTAL-DSDX202003017.htm

    Sun JG, Li MX, Yang ZZ. First line immunotherapy for advanced non-small cell lung cancer with high expression of PD-L1[J]. Di-san Junyi Daxue Xuebao, 2020, 42: 314-319. https://www.cnki.com.cn/Article/CJFDTOTAL-DSDX202003017.htm
    [3]
    Abe M, Tsushima K, Ikari J, et al. Evaluation of the clinical characteristics of everolimus- induced lung injury and determination of associated risk factors[J]. Respir Med, 2018, 134: 6-11. DOI: 10.1016/j.rmed.2017.11.009
    [4]
    王绿化, 傅小龙, 陈明, 等. 放射性肺损伤的诊断与治疗[J]. 中华放射肿瘤学杂志, 2015, 24: 4-9. DOI: 10.3760/cma.j.issn.1004-4221.2015.01.003

    Wang LH, Fu XL, Chen M, et al. Diagnosis and treatment of radiation-induced lung injury[J]. Zhonghua Fangshe Zhongliuxue Zazhi, 2015, 24: 4-9. DOI: 10.3760/cma.j.issn.1004-4221.2015.01.003
    [5]
    Kohno N, Akiyama M, Kyoizumi S, et al. Detection of solubletumor-associated antigen in sera and effusions using novelmonoclonal antibodies, KL-3 and KL-6, against lungadeno-carcinoma[J]. Jpn J Clin Oncol, 1988, 18: 203-216.
    [6]
    Ballester B, Milara J, Cortijo J. Mucinsas a New Frontier inPulmonaryFibrosis[J]. J Clin Med, 2019, 8: 1447. DOI: 10.3390/jcm8091447
    [7]
    Ishikawa N, Hattori N, Yokoyama A, et al. Utility of KL-6/MUC1 in the clinical management of interstitial lung diseases[J]. Respir Investig, 2012, 50: 3-13. DOI: 10.1016/j.resinv.2012.02.001
    [8]
    Kubo K, Azuma A, Kanazawa M, et al. Consensus state-ment for the diagnosis andtreatment of drug-induced lung injuries[J]. Respir Investig, 2013, 51: 260-277. DOI: 10.1016/j.resinv.2013.09.001
    [9]
    中国临床肿瘤学会指南工作委员会. 中国临床肿瘤学会(CSCO)原发性肺癌诊疗指南2019[M]. 北京: 人民卫生出版社, 2019: 1-18.
    [10]
    周惠琼, 张奉春. 涎液化糖链抗原-6在间质性肺疾病诊疗中的价值[J]. 协和医学杂志, 2018, 9: 207-212. DOI: 10.3969/j.issn.1674-9081.2018.03.004

    Zhou HQ, Zhang FC. The value of Kreb von den lungen-6 in the diagnosis and treatment of interstitial lung disease[J]. Xiehe Yixue Zazhi, 2018, 9: 207-212. DOI: 10.3969/j.issn.1674-9081.2018.03.004
    [11]
    Peng DH, Luo Y, Huang LJ, et al. Correlation of Krebs von den Lungen-6 and fibronectin with pulmonary fibrosis in coronavirus disease 2019[J]. Clin Chim Acta, 2021, 517: 48-53. DOI: 10.1016/j.cca.2021.02.012
    [12]
    Bergantini L, Bargagli E, d'Alessandro M, et al. Prognosticbioindicatorsin severe COVID-19 patients[J]. Cytokine, 2021, 141: 155455. DOI: 10.1016/j.cyto.2021.155455
    [13]
    Scotto R, Pinchera B, Perna F, et al. Serum KL-6 Could Represent a Reliable Indicator of Unfavourable Outcome in Patients with COVID-19 Pneumonia[J]. Int J Environ Res Public Health, 2021, 18: 2078. DOI: 10.3390/ijerph18042078
    [14]
    Iwata H, Shibamoto Y, Baba F, et al. Correlation between the serum KL-6 level and the grade of radiation pneumonitis after stereotactic body radiotherapy for stage I lung cancer or small lung metastasis[J]. Radiother Oncol, 2011, 101: 267-270. DOI: 10.1016/j.radonc.2011.05.031
    [15]
    Matsuno Y, Satoh H, Ishikawa H, et al. Simultaneous measurements of KL-6 and SP-D in patients undergoing thoracic radiotherapy[J]. Med Oncol, 2006, 23: 75-81. DOI: 10.1385/MO:23:1:75
    [16]
    Tanaka S, Hattori N, Ishikawa N, et al. Krebs von den Lungen-6 (KL-6) is a prognostic biomarker in patients with surgically resected nonsmall cell lung cancer[J]. Int J Cancer, 2012, 130: 377-387. DOI: 10.1002/ijc.26007
    [17]
    Ishikawa N, Hattori N, Yokoyama A, et al. Usefulness of monitoring the circulating Krebs von den Lungen-6 levels to predict the clinical outcome of patients with advancednon-small cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors[J]. Int J Cancer, 2008, 122: 2612-2620. DOI: 10.1002/ijc.23411
    [18]
    Ogawa Y, Ishikawa T, Ikeda K, et al. Evaluation of serum KL-6, a mucin-like glycoprotein, as a tumor marker for breast cancer[J]. Clin Cancer Res, 2000, 6: 4069-4072. http://www.ncbi.nlm.nih.gov/pubmed/11051258
    [19]
    Inata J, Hattori N, Yokoyama A, et al. Circulating KL-6/MUC1 mucin carrying sialyl Lewisa oligosaccharide is an independent prognostic factor in patients with lung adenocarcinoma[J]. Int J Cancer, 2007, 120: 2643-2649. DOI: 10.1002/ijc.22613
    [20]
    Kawase S, Hattori N, Ishikawa N, et al. Change in serum KL-6 level from baseline is useful for predicting life-threatening EGFR-TKIs induced interstitial lung disease[J]. Respir Res, 2011, 12: 97. DOI: 10.1186/1465-9921-12-97
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