Hui-Yang Zhou

Hui-Yang Zhou is with Xining First People's Hospital,No.10 PoYang Lake Road,No.3,Huzhu Alley,Lirang Street Chengzhong District,Xining,810099,China.E-mail:iamqhzhy@163.com (Corresponding author).

Abstract—Due to factors such as smoking and air pollution,the incidence and mortality of chronic obstructive pulmonary disease (COPD) and lung cancer have remained high for a long time.The stimulus factors between the two diseases are similar,and the biological mechanisms also have certain similarities.Summarize the relationship between Chronic obstructive pulmonary disease and lung cancer from four aspects:inflammation,genetic predisposition,epithelialmesenchymal transition and extracellular matrix.Provide a certain basis for the management of respiratory diseases.

Key words—COPD,Lung cancer,Pathogenesis,Inflammation,Genetic predisposition,EMT,Extracellular matrix

CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Chronic obstructive pulmonary disease (COPD) is common worldwide and causes a significant healthcare burden.Current studies believe that COPD is caused by abnormal airway of chronic bronchitis and peripheral loss of lung parenchymal tissue in emphysema,which may be caused by a variety of cells with different genetic backgrounds and pathophysiological changes.Due to the medical conditions in certain regions,the global prevalence of COPD is always uncertain [1].The 2015 Global Burden of Disease Study estimated that the global prevalence of COPD was approximately 174 million cases [2].In WHO’s 2019 Global Health Estimates,chronic obstructive pulmonary disease ranks third.The number of deaths from tracheal cancer,bronchial cancer and lung cancer has risen from 1.2 million to 1.8 million,and currently ranks sixth among the leading causes of death.

Smoking is the main cause of chronic obstructive pulmonary disease worldwide.Although the proportion of people who smoke has declined,environmental particulate pollution and occupational exposure to second-hand smoke have increased significantly [3,4].As one of the chronic diseases,the high incidence of COPD brings high mortality.Controlling the development of COPD and reducing the number of cases of COPD is one of the problems that currently need to be solved by medicine.

LUNG CANCER

According to the latest data released by the International Agency for Research on Cancer in 2020,lung cancer has the highest mortality rates among all cancers worldwide.And the incidence of lung cancer was 11.4%,second only to breast cancer at 11.7% [5].Among all cancer cases,the incidence and mortality of lung cancer among women are the third and second respectively.However,the incidence and mortality of lung cancer among men have reached the first place.According to histological differences,lung cancer can be divided into two categories:small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC).Among them,NSCLC accounts for about 85% of lung cancers and can be further divided into adenocarcinoma,squamous cell carcinoma and large cell carcinoma [6].SCLC,also known as “oat cell carcinoma”,accounts for about 15% of lung cancers.Due to its rapid growth,high degree of malignancy,strong invasive ability,and easy resistance to radiotherapy and chemotherapy,SCLC is the subtype with the highest fatality rate among all lung cancers [7].

There are many factors that cause lung cancer,and smoking is one of the most important factors.The survey shows that 32.7% of the cancer death rate for men is due to smoking,which is much higher than the 2.4% for women[8].The second important factor is environmental factors.People who are exposed to certain special dust environment all year round have an increased possibility of pulmonary fibrosis.Pulmonary fibrosis and lung cancer are mutually dangerous,and the prevalence of lung cancer is greatly increased [9].

PATHOGENESIS LINKING COPD AND LUNG CANCER

According to clinical statistics,most COPD patients,especially those with milder illnesses,die from other causes.There are two main reasons:lung cancer and cardiovascular disease [10,11].COPD patients with predominantly emphysema have a higher risk of lung cancer than patients with major airway type diseases [12-14].In patients with COPD smokers,the higher incidence of lung cancer than smokers without the COPD doubled[15].

Inflammation

In the pathogenesis of COPD and lung cancer,the participation of NF-κB signaling pathway plays an important role.The expression of NF-κB in airway mucosal biopsy in COPD patients is increased,and the NFκB signaling pathway in lung cancer patients is also abnormally activated [16,17].Signal Transducers and Activators of Transcription 3 (STAT3) is another proinflammatory transcription factor.Compared with normal people,the expression of STAT3 in lung tissues of COPD increased,and further increased in lung cancer tissues [18].

Genetic predisposition

In recent years,many studies have shown that certain genes are closely related to the occurrence of COPD and lung cancer,such as SERPINA1,SERPINE2,Hedgehog interacting protein (HHIP) and family with sequence similarity 13,member A (FAM13A) [19-22].In addition,DNA methylation can promote the occurrence of lung cancer by changing the expression of oncogenes and tumor suppressor genes.CDKN2A is one of the common methylation markers between COPD and lung cancer [23].

Epithelial mesenchymal transition

Epithelial-mesenchymal transition (EMT) represents the transformation of cells with a pro-epithelial phenotype into cells with a mesenchymal phenotype [24].EMT is involved in tumor growth and invasion,and evidence of its existence is also found in the cells of the basal bronchial epithelial layer and respiratory basement membrane of COPD patients.

The extracellular matrix

MMP9 is produced by a variety of cells in the lung.MMP9 can improve the elastic decomposition ability of alveolar macrophages [25].MMP9 derived from macrophages and neutrophils is essential for tumor angiogenesis [27].MMP1 is a kind of interstitial collagenase,which helps the growth of most solid tumors and promotes the formation of metastases.At the same time,MMP1 is also one of the most highly expressed genes in alveolar macrophages of patients with COPD [28].

CONCLUSION

COPD is one of the major diseases that cause human death.Lung cancer is the first cause of human cancer deaths.Although smoking is one of the main causes of most cases of COPD and lung cancer,we should find the common mechanisms and differences between the two diseases in a deeper level.Especially for COPD patients,while actively screening for diagnosis and treatment,more attention should be paid to the monitoring of lung cancer and other major diseases.

ACKNOWLEDGMENT

The authors did not receive any funding for this study.