Expression And Clinical Significance Of Runx1 In Non-small Cell Lung Cancer

BackgroundNon-small cell lung cancer(NSCLC)is one of the most common types of lung cancer globally.According to the World Health Organization(WHO),approximately 3 million people worldwide are diagnosed with lung cancer every year,of which approximately 85%are NSCLC.Most patients are diagnosed at intermediate to advanced stages,with poor treatment outcomes and low survival rates.Despite advances in chemotherapy,radiotherapy,and targeted therapies,the overall survival of NSCLC patients remains low.In recent years,research on the tumor microenvironment(TME)has continued to deepen.TME is a complex network of interactions between immune cells and extracellular matrix,including immune cells,blood vessels,extracellular matrix,fibroblasts,lymphocytes,and signaling molecules around the tumor.Different types of immune cells have become a research hotspot in tumor treatment and prognosis.With the deepening of clinical research,Immune checkpoint inhibitors(ICIs)have been successful in providing significant benefits to a subset of patients in long-term,durable remission and have become an important component of treatment for NSCLC patients,improving survival and anti-tumor response compared to conventional chemotherapy,and monoclonal blocking antibodies against immune checkpoint molecules are Novel immunotherapies against monoclonal blocking antibodies against immune checkpoint molecules have achieved durable long-term responses in NSCLC patients,Immunotherapy targeting PD-L1 has been applied clinically and has achieved certain therapeutic effects,but clinical immunotherapy is prone to drug resistance.Thus requiring the development of better tumor microenvironment(TME)biomarkers to provide more precise treatment for NSCLC patients.The RUNX gene family plays a crucial role in tumor immunosuppression,biological phenotyping,tumorigenesis,progression,metastasis,therapeutic efficacy,and patient prognosis through direct and indirect effects.Runt-related transcription factor 1(Runx1)is one of the Runt family proteins(Runx1,Runx2,and Runx3),which forms a heterodimeric complex with core binding factor β(CBFβ)to enhance the transcription of the RUNX gene family by stimulating the DNA binding ability and stability of the family proteins.Runx1 can cause various leukemias and act as an oncogene in various solid tumors.Many studies have shown that CAFs have become important regulators of anti-tumor immune responses,and many preclinical studies have shown that CAFs may be selected as emerging targets for anti-cancer immunotherapy.At present,there are relatively few studies on the expression of Runx1 in tumor cells and CAFs in NSCLC at home and abroad.There is no joint study on the relationship between Runx1 and immune cell infiltration in the tumor microenvironment,nor the relationship between it and PD-L1 expression.In this experiment,we used a retrospective study to investigate the expression of Runx1 in tumor cells and cancerassociated fibroblasts in NSCLC.ObjectiveTo investigate the differences of Runx1 expression in NSCLC tumor cells and cancer-associated fibroblasts,and to explore the relationship between Runx1 expression in tumor cells and cancer-associated fibroblasts and the clinicopathological characteristics of NCSLC,tumor-associated immune cells,and PDL1 expression,to provide a theoretical basis for precision treatment and immunotherapy for NSCLC patients.MethodSpecimens were collected from NSCLC patients who underwent surgical resection and were diagnosed at Huaihe Hospital of Henan University,from January 2020 to December 2021.Among them were 168 cases of tumor tissues and 98 cases of adjacent normal tissues(located>3cm away from the tumor).Immunohistochemistry was used for comparative analysis to observe the expression characteristics of Runx1 in NSCLC tumor tissues and the tumor microenvironment,and to analyze its relationship with clinical pathological features of patients,tumor-associated immune cells,and PD-L1 expression.The aim is to explore the clinical value of Runx1 in diagnosing and treating non-small cell lung cancer.Results1.The positive rate of Runx1 in NSCLC tumor tissue was 66.1%(111/168),and it was not expressed in normal lung tissue(0/98),the difference was statistically significant(P<0.001).2.The expression of Runx1 in NSCLC tumor tissues was correlated with age,tumor size and histological type,and the difference was statistically significant(P<0.05);while it was correlated with gender,degree of differentiation,capsule invasion,lymph node metastasis,family history,smoking history,and tumor location,the difference was not significant(P>0.05).3.The positive rate of Runx1 for CAFs in NSCLC was 97.6%(164/168),and it was not expressed in normal lung tissue(0/98),with a statistically significant difference(P<0.001).4.Runx1 expression of CAFs in NSCLC correlated with gender,histological type,and degree of differentiation,with statistically significant differences(P<0.05);while the differences with patient age,tumor size,perineural invasion,lymph node metastasis,tumor site,family history,smoking history,and TNM staging were not significant(P>0.05).5.Runx1 expression of CAFs in NSCLC correlated with infiltrative expression of helper T cells,cytotoxic T cells,and Foxp3+Tregs with statistically significant differences(P<0.05);while the differences with CD 163+tumor-associated macrophage infiltration were not significant(P>0.05).6.Runx1 expression in NSCLC cancer-associated fibroblasts was statistically different from that of PD-L1(p<0.001).Conclusions1.Runx1 protein was expressed in NSCLC tumor tissues,in tumor mesenchymal cancer-associated fibroblasts,and not in paraneoplastic lung tissues and interstitium,suggesting that Runx1 is closely associated with the development of non-small cell lung cancer.2.The high expression of Runx1 protein in cancer-associated fibroblasts interacts with tumorassociated immune cells to jointly promote tumor progression.3.Runx1 protein expression in cancer-associated fibroblasts was positively correlated with PD-L1 expression.