The significance of serum sRAGE combined with lung function and lung HRCT in predicting risk of COPD with NSCLC_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

MA Honghong ¹ ^马 , WANG Xi ² ^马 , XIE Xinyun ³ , YUAN Qun ² , ZHUAN Bing ¹ ,  YANG Zhao ²

1. Department of Respiratory Medicine, Ningxia Hui Autonomous Region People's Hospital, Yinchuan, Ningxia 750001, P. R. China;
2. Department of Respiratory Medicine, Suzhou Science & Technology City Hospital, Suzhou, Jiangsu 215153, P. R. China;
3. Department of Respiratory Oncology, The Sixth People's Hospital of Chengdu, Chengdu, Sichuan 610051, P. R. China;

Corresponding author：

YANG Zhao, Email: greentree66611@sina.com

Keywords：

Chronic obstructive pulmonary disease; non-small cell lung cancer; emphysema; lung function; soluble receptor of advanced glycation endproducts; high resolution computed tomography

DOI：

10.7507/1671-6205.202305026

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Objective To observe the value of serum soluble receptor of advanced glycation endproducts (sRAGE) combined with lung function and high resolution lung CT (HRCT) in predicting the risk of chronic obstructive pulmonary disease (COPD) developing non-small cell lung cancer (NSCLC). Methods From January 2019 to June 2021, 140 patients with COPD combined with NSCLC, 137 patients with COPD, and 133 patients with NSCLC were enrolled in the study from the People's Hospital of Ningxia Hui Autonomous Region. General data, clinical symptoms, pulmonary function indexes and HRCT emphysema indexes (EI) were collected. Serum sRAGE levels of these patients were measured by enzyme linked immunosorbent assay. Clinical characteristics of patients with COPD complicated with NSCLC were analyzed. Serum sRAGE, lung function and lung HRCT were combined to evaluate the correlation between the degree of emphysema and the occurrence of NSCLC in COPD, and receiver operator characteristic (ROC) curve analysis was performed for diagnostic efficiency. Results Compared with NSCLC group, COPD combined with NSCLC group had higher proportion of male patients, higher proportion of elderly patients, higher smoking index, and higher proportion of squamous cell carcinoma (P<0.05). FEV₁ and FEV₁%pred in COPD combined with NSCLC group were significantly lower than those in COPD group and NSCLC group. The Goddard score and EI values of emphysema were significantly increased (P<0.05). Serum sRAGE was significantly lower than that of COPD group and NSCLC group (P<0.05). Serum sRAGE level was positively correlated with FEV₁%pred (r=0.366, P<0.001) and FEV₁/FVC (r=0.419, P<0.001), and negatively correlated with Goddard score (r=–0.710, P=0.001) and EI value (r=–0.515, P<0.001). Binary multi-factor logistic regression analysis showed that age, smoking index, EI, Goddard score, RV/TLC were positively correlated with the risk of COPD developing NSCLC, while FEV₁%pred, FVC, FEV₁/FVC and serum sRAGE were negatively correlated with the risk of COPD developing NSCLC. ROC curve results showed that the area under the curve (AUC) of single diagnosis of sRAGE was 0.990, and the optimal cut-off value of 391.98 pg/mL with sensitivity of 93.3% and specificity of 89.7%. The AUC of sRAGE combined with age, smoking index, EI, Goddard score, FEV₁%pred, FVC, FEV₁/FVC, RV/TLC was 1.000 with sensitivity of 96.7%, specificity of 96.6%, and Yoden index of 0.933. Conclusion The combination of serum sRAGE, lung function and HRCT emphysema score can improve prediction of NSCLC occurrence in COPD.

Citation： MA Honghong, WANG Xi, XIE Xinyun, YUAN Qun, ZHUAN Bing, YANG Zhao. The significance of serum sRAGE combined with lung function and lung HRCT in predicting risk of COPD with NSCLC. Chinese Journal of Respiratory and Critical Care Medicine, 2023, 22(7): 457-463. doi: 10.7507/1671-6205.202305026 Copy

1.	崔亚楠, 陈平, 陈燕. 2018年版慢性阻塞性肺疾病全球倡议诊断及处理和预防策略解读. 中华结核和呼吸杂志, 2018, 41(3): 236-239.
2.	Siegel RL, Miller KD, Fuchs HE, et al. Cancer Statistics, 2021. CA Cancer J Clin, 2021, 71(1): 7-33.
3.	Park HY, Kang D, Shin SH, et al. Chronic obstructive pulmonary disease and lung cancer incidence in never smokers: a cohort study. Thorax, 2020, 75(6): 506-509.
4.	Husebø GR, Nielsen R, Hardie J, et al. Risk factors for lung cancer in COPD - results from the Bergen COPD cohort study. Respir Med, 2019, 152: 81-88.
5.	Labaki WW, Xia M, Murray S, et al. Quantitative emphysema on low-dose CT imaging of the chest and risk of lung cancer and airflow obstruction: an analysis of the National Lung Screening Trial . Chest, 2021, 159(5): 1812-1820.
6.	Serban KA, Pratte KA, Bowler RP. Protein biomarkers for COPD outcomes. Chest, 2021, 159(6): 2244-2253.
7.	Hu XL, Xu ST, Wang XC, et al. Status of coexisting chronic obstructive pulmonary disease and its clinic pathological features in patients undergoing lung cancer surgery: a cross-sectional study of 3, 006 cases. J Thorac Dis, 2018, 10(4): 2403-2411.
8.	Media AS, Persson M, Tajhizi N, et al. Chronic obstructive pulmonary disease and comorbidities' influence on mortality in non-small cell lung cancer patients. Acta Oncol, 2019, 58(8): 1102-1106.
9.	Su ZX, Jiang Y, Li CC, et al. Relationship between lung function and lung cancer risk: a pooled analysis of cohorts plus Mendelian randomization study. J Cancer Res Clin Oncol, 2021, 147(10): 2837-2849.
10.	Carr LL, Jacobson S, Lynch DA, et al. Features of COPD as predictors of lung cancer. Chest, 2018, 153(6): 1326-1335.
11.	Yasuura Y, Terada Y, Mizuno K, et al. Quantitative severity of emphysema is related to the prognostic outcome of early-stage lung cancer. Eur J Cardiothorac Surg, 2022, 62(5): ezac499.
12.	Fortis S, Comellas AP, Bhatt SP, et al. Ratio of FEV₁/slow vital capacity of < 0.7 is associated with clinical, functional, and radiologic features of obstructive lung disease in smokers with preserved lung function. Chest, 2021, 160(1): 94-103.
13.	Parris BA, O'Farrell HE, Fong KM, et al. Chronic obstructive pulmonary disease (COPD) and lung cancer: common pathways for pathogenesis. J Thoracic Dis, 2019, 11(Suppl 17): S2155-S2172.
14.	Forder A, Zhuang R, Souza VGP, et al. Mechanisms contributing to the comorbidity of COPD and lung cancer. Int J Mol Sci, 2023, 24(3): 2859.
15.	Pouwels SD, Hesse L, Wu XH, et al. LL-37 and HMGB1 induce alveolar damage and reduce lung tissue regeneration via RAGE. Am J Physiol Lung Cell Mol Physiol, 2021, 321(4): L641-L652.
16.	袁雪枚, 耑冰, 李萍, 等. 慢性阻塞性肺疾病合并肺动脉高压患者血清活性氧和硫化氢水平及肺组织还原型烟酰胺腺嘌呤二核苷酸氧化酶-4和胱硫醚-γ-裂解酶表达及其意义. 中华内科杂志, 2019, 58(10): 770-776.
17.	王曦, 李萍, 耑冰, 等. RYR2、FKBP12.6及CaMK-Ⅱ在COPD患者肺组织中的表达研究. 国际呼吸杂志, 2020, 40(2): 94-101.
18.	Sharma A, Kaur S, Sarkar M, et al. The AGE-RAGE axis and RAGE genetics in chronic obstructive pulmonary disease. Clin Rev Allergy Immunol, 2021, 60(2): 244-258.
19.	Liao YF, Yin S, Chen ZQ, et al. High glucose promotes tumor cell proliferation and migration in lung adenocarcinoma via the RAGE NOXs pathway. Mol Med Rep, 2018, 17(6): 8536-8541.
20.	Waghela BN, Vaidya FU, Ranjan K, et al. AGE-RAGE synergy influences programmed cell death signaling to promote cancer. Mol Cell Biochem, 2021, 476(2): 585-598.

1. 崔亚楠, 陈平, 陈燕. 2018年版慢性阻塞性肺疾病全球倡议诊断及处理和预防策略解读. 中华结核和呼吸杂志, 2018, 41(3): 236-239.
2. Siegel RL, Miller KD, Fuchs HE, et al. Cancer Statistics, 2021. CA Cancer J Clin, 2021, 71(1): 7-33.
3. Park HY, Kang D, Shin SH, et al. Chronic obstructive pulmonary disease and lung cancer incidence in never smokers: a cohort study. Thorax, 2020, 75(6): 506-509.
4. Husebø GR, Nielsen R, Hardie J, et al. Risk factors for lung cancer in COPD - results from the Bergen COPD cohort study. Respir Med, 2019, 152: 81-88.
5. Labaki WW, Xia M, Murray S, et al. Quantitative emphysema on low-dose CT imaging of the chest and risk of lung cancer and airflow obstruction: an analysis of the National Lung Screening Trial . Chest, 2021, 159(5): 1812-1820.
6. Serban KA, Pratte KA, Bowler RP. Protein biomarkers for COPD outcomes. Chest, 2021, 159(6): 2244-2253.
7. Hu XL, Xu ST, Wang XC, et al. Status of coexisting chronic obstructive pulmonary disease and its clinic pathological features in patients undergoing lung cancer surgery: a cross-sectional study of 3, 006 cases. J Thorac Dis, 2018, 10(4): 2403-2411.
8. Media AS, Persson M, Tajhizi N, et al. Chronic obstructive pulmonary disease and comorbidities' influence on mortality in non-small cell lung cancer patients. Acta Oncol, 2019, 58(8): 1102-1106.
9. Su ZX, Jiang Y, Li CC, et al. Relationship between lung function and lung cancer risk: a pooled analysis of cohorts plus Mendelian randomization study. J Cancer Res Clin Oncol, 2021, 147(10): 2837-2849.
10. Carr LL, Jacobson S, Lynch DA, et al. Features of COPD as predictors of lung cancer. Chest, 2018, 153(6): 1326-1335.
11. Yasuura Y, Terada Y, Mizuno K, et al. Quantitative severity of emphysema is related to the prognostic outcome of early-stage lung cancer. Eur J Cardiothorac Surg, 2022, 62(5): ezac499.
12. Fortis S, Comellas AP, Bhatt SP, et al. Ratio of FEV₁/slow vital capacity of < 0.7 is associated with clinical, functional, and radiologic features of obstructive lung disease in smokers with preserved lung function. Chest, 2021, 160(1): 94-103.
13. Parris BA, O'Farrell HE, Fong KM, et al. Chronic obstructive pulmonary disease (COPD) and lung cancer: common pathways for pathogenesis. J Thoracic Dis, 2019, 11(Suppl 17): S2155-S2172.
14. Forder A, Zhuang R, Souza VGP, et al. Mechanisms contributing to the comorbidity of COPD and lung cancer. Int J Mol Sci, 2023, 24(3): 2859.
15. Pouwels SD, Hesse L, Wu XH, et al. LL-37 and HMGB1 induce alveolar damage and reduce lung tissue regeneration via RAGE. Am J Physiol Lung Cell Mol Physiol, 2021, 321(4): L641-L652.
16. 袁雪枚, 耑冰, 李萍, 等. 慢性阻塞性肺疾病合并肺动脉高压患者血清活性氧和硫化氢水平及肺组织还原型烟酰胺腺嘌呤二核苷酸氧化酶-4和胱硫醚-γ-裂解酶表达及其意义. 中华内科杂志, 2019, 58(10): 770-776.
17. 王曦, 李萍, 耑冰, 等. RYR2、FKBP12.6及CaMK-Ⅱ在COPD患者肺组织中的表达研究. 国际呼吸杂志, 2020, 40(2): 94-101.
18. Sharma A, Kaur S, Sarkar M, et al. The AGE-RAGE axis and RAGE genetics in chronic obstructive pulmonary disease. Clin Rev Allergy Immunol, 2021, 60(2): 244-258.
19. Liao YF, Yin S, Chen ZQ, et al. High glucose promotes tumor cell proliferation and migration in lung adenocarcinoma via the RAGE NOXs pathway. Mol Med Rep, 2018, 17(6): 8536-8541.
20. Waghela BN, Vaidya FU, Ranjan K, et al. AGE-RAGE synergy influences programmed cell death signaling to promote cancer. Mol Cell Biochem, 2021, 476(2): 585-598.

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