Expression And Prognostic Significance Of Plexin-A4 And PD-1 In Esophageal Squamous Cell Carcinoma

BackgroundEsophageal cancer has become a common malignant tumor of digestive tract all over the world.The pathogenesis of esophageal cancer is related to fast diet,excessive heat,smoking,drinking,genetic and nitrite stimulation.More than 90%of esophageal carcinoma was squamous cell carcinoma.Its early clinical characteristics are not obvious,such as dysphagia and other symptoms,most of them are in the middle and late stage of the disease.Surgery is the main treatment for esophageal cancer.For the patients who have lost the opportunity of operation,conservative methods such as radiotherapy and chemotherapy should be used,but the therapeutic effect is poor,the quality of life is poor,and the survival time is short.Immunotherapy as a new therapy has achieved initial results.Therefore,it is of great significance to detect tumor progression by immunomarkers such as Plexin-A4 and programmed death-1（PD-1）.ObjectiveBy detecting the expression of Plexin-A4 and PD-1 in esophageal squamous cell carcinoma,the relationship between them and clinicopathological features,prognosis and independent risk factors of patients with esophageal squamous cell carcinoma were analyzed,and the general rules were summarized,hoping to provide new targets and ideas for immunotherapy of esophageal carcinoma.MethodsReal time quantitative reverse transcription polymerase chain reaction（RT-q PCR）was used to detect the expression of Plexin-A4 and PD-1 genes in 20 cases of fresh esophageal squamous cell carcinoma and adjacent tissues.The corresponding mRNA expression was calculated by 2^-△△Ctmethod,and the dot like distribution of mRNA expression was depicted by graphpad 5.0 software,The expression of Plexin-A4 and PD-1in 80 cases of esophageal squamous cell carcinoma was detected by immunohistochemistry,By cell staining,the negative and positive expression patterns were summarized,and the correlation betweenχ²Analysis and clinicopathological characteristics was used for qualitative detection;Kaplan Meier method was used to analyze the relationship between the survival time of patients with esophageal squamous cell carcinoma and different differentiation degree,lymph node metastasis and positive expression of Plexin-A4 and PD-1;Cox univariate and multivariate models were used Methods the independent Prognostic risk factors were analyzed and determined.ResultsThe expression of PD-1 mRNA in ESCC（X±S=1.47±0.99）was significantly higher than that in adjacent tissues（X±S=0.48±0.32）,with statistical significance;the expression of Plexin-A4 mRNA in ESCC（X±S=0.95±0.62）was slightly higher than that in adjacent tissues（X±S=0.36±0.26）with statistical significance.Immunohistochemistry showed that the staining of Plexin-A4 was deeper in the cytoplasm of ESCC,PD-1 was deeper in the cytoplasm and cell membrane of ESCC,and lighter or almost no staining was found in normal esophageal mucosa 5cm adjacent to the cancer.According to the analysis of different clinicopathological characteristics,the expression of Plexin-A4 protein was significantly correlated with the degree of invasion（P=0.011）;the expression of PD-1protein was significantly correlated with age（P=0.004）,degree of invasion（P=0.021）,and lymph node metastasis（P=0.024）.The median survival time of patients with ESCC was significantly correlated with the degree of differentiation（P=0.006）,lymph node metastasis（P=0.001）and positive expression of PD-1（P=0.002）,but not with the positive expression of Plexin-A4（P=0.227）.Cox multivariate analysis showed that differentiation,lymph node metastasis and PD-1 expression were independent risk factors for the prognosis of ESCC.ConclusionThe expression levels of PD-1 and Plexin-A4 were up-regulated in esophagealsquamous cell carcinoma compared with adjacent tissues,especially PD-1.PD-1 can be used as an important target and prognostic indicator of esophageal squamousimmunotherapy.