The Expression Of Nerve Growth Factor And Tyrosine Kinase Receptor A In Esophageal Squamous Cell Carcinoma Tissue And Its Clinical Significance

Objective :Esophageal squamous cell carcinoma(ESCC)is a challenging disease,and the search for new molecular markers and novel therapeutic targets for ESCC has been intensely pursued.Nerve growth factor(NGF)is a soluble protein that acts primarily by binding to two receptors,tyrosine kinase receptor A(Trk A)and p75 neurotrophin receptor(p75NTR).Several studies have now reported that NGF together with Trk A promote tumor cell growth and invasion by activating signaling pathways in a variety of malignancies.However,studies about NGF and Trk A in ESCC have not been reported in China.In this study,we investigated the possibility of NGF and Trk A becoming new molecular markers for ESCC by examining the relationship between the expression levels of NGF and Trk A in ESCC tissues and clinicopathological factors.Methods: Gene expression profiling(GEPIA)was used to retrieve gene expression profiles comparing NGF with Neurotrophin receptor kinase1(NTRK1)(i.e.,the gene encoding Trk A)in esophageal cancer from the Cancer Genome Atlas TCGA and genotype tissue expression GTEX databases Correlations of PIK3R1,PTEN,AKT1,AKT2,Akt3.We collect 10 fresh esophageal squamous cell carcinoma tissues and normal tissue samples from patients undergoing radical resection of esophageal cancer at Taizhou People’s Hospital from 2022 to 2023.Then detect the m RNA expression levels of NGF and Trk A in esophageal squamous cell carcinoma tissues and normal tissues using q PCR,and perform statistical analysis using T-test.Wax block samples of pathological tissues from 80 ESCC patients who underwent curative resection of esophageal cancer at the Tai Zhou People’s Hospital between 2018 and 2019,including cancer and normal tissues,and clinicopathological data of the 80 patients,including age,gender,TNM stage,tumor grade,intravascular tumor thrombus,and nerve invasion,were collected.The expression levels of NGF and Trk A in ESCC tissues versus normal tissues were assessed by immunohistochemical staining,and the relationships between the expression levels and clinicopathological factors including age,gender,TNM stage,tumor grade,intravascular tumor thrombus,and nerve invasion were analyzed by statistical methods using chi square tests.Clinicopathological parameters and the prognostic effects of NGF versus Trk A in ESCC were investigated by univariate versus multivariate Cox regression analysis,and NGF versus Trk A were explored for molecular typing of ESCC.Results: NGF gene expression was significantly correlated with PIK3CA(P =0.0041),AKT1(P = 0.0058),and Akt3(P = 5.4e-6)in esophageal cancer between TCGA and GTEX database,with statistical significance at P < 0.05.No statistically significant difference was observed in m RNA expression of NGF between ESCC and normal tissues(P = 0.124)and Trk A between ESCC and normal tissues(P = 0.192).NGF was expressed in both ESCC and normal tissues,and the positive findings of staining were localized to the cell membrane and cytoplasm,although 63.7%(51 / 80)of the 80 ESCC samples with high NGF expression were higher than that in normal tissues(32.5%),but there was no significant difference.NGF expression in ESCC tissues was not significantly correlated with gender,N stage,M stage,tumor grade,intravascular tumor thrombus,and perineural invasion,while it was significantly correlated with age(P = 0.007),T stage(P = 0.004),P < 0.05.Trk A is expressed in both ESCC and normal tissues,localizes to the cell membrane and cytoplasm,and the level of Trk A expression in ESCC is statistically significantly different(P = 0.000),P <0.05.Trk A expression in ESCC tissues was not significantly correlated with gender,age,T stage,N stage,M stage,intravascular tumor thrombus,and nerve invasion,while it was significantly correlated with tumor grade(P = 0.002),P <0.05.The difference between NGF and Trk A expression in ESCC of different TNM stages was not found to be statistically significant,nor was the effect of expression levels of NGF and Trk A in ESCC of different TNM stages on three-year survival.T stage was an independent prognostic factor for ESCC(P = 0.002)with P < 0.05,which was statistically significant.Conclusions: NGF gene expression was significantly correlated with PIK3CA(P= 0.0041),AKT1(P = 0.0058),and Akt3(P = 5.4e-6)in esophageal cancer from TCGA versus GTEX database.No statistically significant difference was observed in m RNA expression of NGF between ESCC and normal tissues(P =0.124)and Trk A between ESCC and normal tissues(P = 0.192).Both NGF and Trk A were expressed in the cell membrane and cytoplasm of ESCC cells,and Trk A expression was significantly higher in ESCC than in normal tissues(P =0.000).Higher expression of NGF in ESCC tissues suggested younger age(P =0.007)and suggested later T stage(P = 0.004).High expression of Trk A in ESCC tissues suggested better tumor differentiation(P = 0.002).Multivariate analysis revealed that the depth of tumor invasion was an independent prognostic factor for ESCC(P = 0.001).The above results suggest that NGF and Trk A may be a new potential molecular marker for ESCC.