The Expression Of Inflammatory Immune Pathway Molecules In Non-small Cell Lung Cancer And Correlation Of PDL1 Antibody Efficacy

Background:Lung cancer is a common malignant tumor in China,and its morbidity and mortality are all ranked first in the country.The main pathological types are divided into small cell lung cancer?SCLC?and non-small cell lung cancer?NSCLC?,which are characterized by high malignancy,invasiveness,easy metastasis,poor prognosis and recurrence^[1].The treatment is mainly combined with surgical resection and chemotherapy,radiotherapy,etc.The five-year survival rate of lung cancer is still less than 15%.With the development of medical treatment technology,especially the development of immunotherapy,prolongs the overall survival of lung cancer patients,the 5-year survival rate has not been significantly improved.Therefore,it is particularly important to improve the killing effect of targeted therapy on tumors by changing the immune microenvironment of tumors^[2].With the study of the tumor microenvironment,inflammation-related signaling pathways play an important role in the occurrence and development of tumors^[3].Recent studies have shown that hypoxia inducible factor-1?HIF-1?,Vascular Endothelial Growth Factor Receptor?VEGFR?,nuclear factor kappa B?nuclear factor kappa-B,NF?-?B),phosphorylation-signal transducers and Activators Of Transcription?p-STAT3?and other inflammatory signaling pathway molecules not only have a leading role in chronic inflammation,but also play an important role in the occurrence and metastasis of some solid tumors^[4].In addition to promoting tumor cell proliferation and blocking tumor cell apoptosis,HIF-1?can also mediate immunosuppression.Inflammation is the natural immune process of the body to physiology,mechanism and oxidative stress,and is closely related to the activation of the classical NF-?B signaling pathway.STAT 3 not only plays an important role in the proliferation,survival,invasion and immunosuppression of tumor cells,but also promotes cancer through factors such as inflammation,obesity and stem cells.VEGFR is an angiogenic growth factor receptor.Tumor cells need abundant blood supply to provide sufficient nutrition during the process of occurrence,proliferation and metastasis.VEGFR is closely related to tumor angiogenesis.The four inflammation-related signaling pathway molecules play a"two-way"role in the microenvironment of the tumor,and the effects of inflammation-related molecules on tumors at different timings are also quite different.With the deepening of immunotherapy research,the killing effect of programmed cell death protein ligand-1?PDL-1?immunosuppressive agents in cancer is exciting.PD-1 and PDL-1 have become a milestone in the process of cancer immunotherapy.The expression of PDL-1 impairs T cell function by binding to its receptor PD-1 on the surface of T cells.Therefore,the application of PDL-1 inhibitor can reduce the immune escape of tumors and play a role in killing tumors[5].Purpose:Whether it can interfere with inflammation-related molecules,let the inflammation-related molecules can be in a state of killing tumors for a long time.Or synergistic killing of tumor cells with related targeted drugs,and reducing the resistance of tumor cells to targeted drugs has become a research hotspot.Although there have been a lot of reports on killing tumor cells by using small molecule inhibitors such as STAT3,NF-?B,HIF-1,VEGFR,etc.,it can synergize with targeted drugs to exert stronger killing effect on tumor cells and reduce tumors.Inhibitors of cell-to-target drug resistance and a significant improvement in the prognosis of cancer patients are still under investigation.Therefore,screening important inflammation-related molecules,by changing the inflammatory microenvironment of tumors,is particularly important in combination with PDL-1 antibodies to synergistically kill tumor cells,and molecular mechanisms can provide strategies for the development of new anti-tumor drugs.Method:In this study,48 patients in our hospital were randomly selected with informed consent,and patients with non-small cell lung cancer who were treated with PDL-1antibody in the middle and late stage were included.The names,ages,genders,organization type and date were marked.All specimens were subjected to non-biotin immunohistochemical staining to detect the expression of inflammatory factors of p-STAT3,NF-?B P65,HIF-1?,VEGFR protein and PDL-1 in tissues.The expression of HIF-1?and PDL-1 was mainly located in the cytoplasm,and the high expression was brown-yellow.The expression of p-STAT3 and NF-?B P65 was mainly located in the nucleus,and the brown-yellow particles appeared in the high-stained part.The expression of VEGFR was mainly located in the cell membrane,which highly expressed parts of the stain appeared in brownish yellow particles.The image-pro plus 6.0 image analysis software was used to determine the cumulative optical density?IOD?of immunohistochemical images,which was used for statistical analysis by spss20.0 software.Result:1.The relationship between the expression of HIF-1?,VEGFR,NF-?B P65,p-STAT3,PDL-1 and clinicopathological featuresThe expression of HIF-1?was correlated with stage and pathological type.The expression of VEGFR was related to stage.The expression of NF-?B P65 was correlated with age,stage and pathological type.The expression p-STAT3 and PDL-1were associated with stage.2.The relationship between the efficacy and prognosis of HIF-1?,VEGFR,NF-?B P65,p-STAT3,PDL-1.Univariate survival analysis showed that PFS was associated with stage,PDL-1 availability,HIF-1?,VEGFR,NF-?B P65,p-STAT3 and PDL-1?P<0.05?.Cox multivariate survival analysis showed that staging and p-STAT3 protein expression were independent prognostic factors for PFS?P<0.05?.The expression of p-STAT3may be related to the efficacy of PDL-1 antibody.3.The correlation between HIF-1?,VEGFR,NF-?B P65,p-STAT3 and PDL-1expressionSpearman rank correlation analysis showed that a positive correlation between VEGFR and PDL-1 expression?rs=0.438,P=0.003?and p-STAT3 was positively correlated with PDL-1 expression?rs=0.359,P=0.012?.Conclusion:1.The high protein expression of HIF-1?,VEGFR,NF-?B P65,p-STAT3 and PDL-1 in NSCLC tissues is related to staging.The expression of HIF-1?and NF-?B P65 is related to pathological type,The expression of NF-?B P65 is related to age.2.Univariate analysis of PFS was associated with stage,HIF-1?,VEGFR,NF-?B P65,p-STAT3,and PDL-1 protein expression?p<0.05?.COX multivariate analysis found staging,p-STAT3 protein expression was an independent risk factor for poor prognosis of PFS?p<0.05?,and the expression of p-STAT3 may be related to the efficacy of PDL-1 antibody.3.There is a correlation between VEGFR with PDL-1 and p-STAT3 with PDL-1expression in tissues of patients with advanced NSCLC.