The Possible Role Of Interferon Regulatory Factor 5 In The Development Of Non-small Cell Lung Cancer

Background and objective:Lung cancer is one of the malignant tumors with the highest morbidity and mortality in the world,which is a huge burden on human society.Non-small cell lung cancer(NSCLC)is the most common histopathological type of lung cancer,accounting for about 85%-90% of lung cancer cases.Inflammation is closely related to cancer and has become a major hallmark of cancer.Interferon regulatory factor(IRF)5 is a key transcription factor for the innate immune response signaling pathway,which is involved in regulating the expression of inflammatory factors such as type I interferon(IFN),interleukin(IL)-6,IL-10,tumor necrosis factor(TNF)-? and interferon-?-inducible protein(IP)-10,as well as plays a key regulatory role in macrophage polarization,B lymphocyte activation,proliferation,plasma cell differentiation,and antibody secretion.In addition,IRF5 can also promote cell cytle arrest and apoptosis.The effects of IRF5 in cancer can be cancer type-specific.IRF5 play a tumour suppressor role in breast cancer and liver cancer,but it can promot the development of thyroid cancer and kidney cancer.At present,IRF5 may inhibit the development of NSCLC in vitro.However,the role of IRF5 in the occurrence and development of NSCLC has not been explored from a clinical perspective.This study aims to clarify the expression and role of IRF5 in NSCLC tissues and peripheral blood,providing new ideas and methods for the NSCLC diagnosis and treatment.Methods:IRF5 protein expression in NSCLC tissues was detected by Western blotting.The expression of IRF5 and its related inflammatory factors IL-6,IL-10,TNF-? and IP-10 in peripheral blood of NSCLC patients was detected by RT-q PCR,flow cytometry and CBA.PCR and Sanger sequencing were used to detect the genotypes of IRF5rs77571059 and rs2004640 in NSCLC patients and healthy volunteers.Results:1.The IRF5 protein level in NSCLC tissues was significantly lower than that in the para-carcinoma tissues,especially in patients younger than 45 years and older than60 years.2.The IRF5 protein level in early-stage NSCLC tissues was significantly higher than that in progressive-stage NSCLC,while there was no significant difference between lung adenocarcinoma and lung squamous cell carcinoma.3.The survival time of NSCLC patients with high IRF5 protein level in cancer tissues was longer than that of NSCLC patients with low IRF5 protein level in cancer tissues,although there was no significant statistical difference between the two groups.4.In NSCLC patients with smoking,the IRF5 expression level in cancer tissues was significantly lower than that in para-carcinoma tissues,its level in early-stage cancer tissues was significantly higher than that in progressive-stage cancer tissues,and its level in cancer tissues negatively correlated with smoking years.5.The IRF5 expression level in peripheral blood WBCs of NSCLC patients was significantly higher than that in healthy controls,and the level in early-stage NSCLC patients was significantly higher than that in progressive-stage patients.6.Compared with the healthy controls,the NSCLC diagnostic sensitivity,specificity and AUC value of IRF5 m RNA in peripheral blood WBCs of NSCLC patients were 87.9%,71.4% and 0.858 respectively,and the diagnostic value(AUC =0.904)of IRF5 m RNA in early NSCLC patients was higher than that in advanced NSCLC patients(AUC = 0.81).7.The distribution frequency of IRF5 rs77571059 heterozygous deletion(-/CGGGG)in NSCLC patients was significantly higher than that in healthy controls,and the frequency of allele(CGGGG)distribution was also significantly higher than that in healthy controls,but there was no significant difference between the early and progressive stage.8.IRF5 m RNA levels in peripheral blood of NSCLC patients with IRF5rs77571059 heterozygous(-/CGGGG)were significantly higher than those inhomozygous(-/-)patients.9.The protein levels of IL-6 and IP-10 in NSCLC patient plasma were significantly higher than those in healthy controls,and the IP-10 protein levels in plasma and IL-10 m RNA levels in WBCs of early-stage NSCLC patients were significantly increased,while the IL-6 and IL-10 protein levels in plasma of advanced NSCLC patients were significantly elevated.10.The proportion of IRF5+ WBCs and monocytes in peripheral blood of NSCLC patients all positively correlated with the IP-10 protein level in plasma and negatively correlated with the IL-10 protein level in plasma.Conclusion:1.IRF5 may play a negative regulatory role in the development of NSCLC2.The IRF5 level in peripheral blood WBCs was significantly elevated in early stage NSCLC,suggesting that it played an early warning role in NSCLC development.3.IRF5 SNP rs77571059 was related with the susceptibility of NSCLC and affected the IRF5 m RNA level in peripheral blood WBCs of NSCLC patients,indicating that the genetic background influenced the IRF5 response in NSCLC development.4.The level of IRF5 downstream cytokines in peripheral blood WBCs or plasma was related to NSCLC stage.Monitoring the protein level of IP-10 in plasma and the m RNA level of IL-10 in peripheral blood WBCs had auxiliary effect on the early prediction of lung cancer.