Clinical Significance Of Downregulated CD70 And CD27 Expression In Poor Prognosis Of Esophageal Squamous Cell Carcinoma

Objective Surgery is the primary way to treat Esophageal cancer,one of the most common malignancies in the world,but the recurrence rate is high.The outcomes in the patients with Esophageal squamous cell carcinoma(ESCC)are limited.Evidence for the antitumor activity of immunocheckpoint inhibitors has also increased in recent years.In this regard,regulating the interaction between CD27 and CD70 may be a novel cancer immunotherapy strategy,and CD27 and CD70 have been reported in breast cancer,liver cancer and other tumors.However,the role of CD27 and CD70 in esophageal squamous cell carcinoma(ESCC)remains unclear.The purpose of this study was to investigate the down-regulation of CD27 and CD70 expression in esophageal squamous cell carcinoma(ESCC)and the role of CD70 in esophageal squamous cell carcinoma(ESCC).Methods 1.We first retrieved the GSE53625 data set of esophageal cancer from the GEO data set WWW.Nlm.nlm.nih.gov/GDS /,which includes the differentially expressed genes in esophageal cancer compared with normal tissues,as well as the clinicopathological parameters,such as age,gender,pathological stage,T stage,N stage and M stage.The differences of CD27 and CD70 expression in tumor tissues and normal tissues were analyzed,and the relationship between CD27 and CD70 m RNA expression levels and patient clinicopathological parameters was analyzed.2.The expression of CD27 and CD70 in esophageal squamous cell carcinoma(ESCC)was evaluated by quantitative polymerase chain reaction(RT-QPCR)and immunohistochemistry.The clinical data were collected and followed up to explore the relationship between survival and prognosis of patients with esophageal squamous cell carcinoma.We also investigated the correlation between CD27 and CD70 expression and immune-related pathways,including CD8+ T cell recruitment,function,and other inhibitory immune checkpoints.Results 1.GSE53625 database analysis results We found that both CD27 and CD70 m RNA levels in ESCC tissues were significantly lower than those in para-cancer normal tissues(P < 0.0001 for both)when compared with matched normal tissues,which was consistent with our Chinese patient cohort.Kaplan-meier curve and log-rank test showed that CD27 m RNA level was significantly correlated with overall quality of life of patients(P = 0.041),and CD70 m RNA level was significantly correlated with overall quality of life of patients(P = 0.047).And we use GSE53625 data set(www.ncbi.nlm.nih.gov/gds/)to assess the patients with ESCC CD27 and CD70 expression and its relationship with clinicopathological parameters.The data set contained two groups of ESCC data: 119 pairs of ESCC and 60 pairs of normal esophageal tissue,respectively.We found that the m RNA levels of CD27 and CD70 in ESCC tissues were lower than those in the normal matched group,and the expression of CD27 was negatively correlated with tumor invasion depth(P = 0.026),but the expression of CD27 and CD70 was not correlated with other clinicopathological parameters.2.Our database analysis results In our patient cohort,we analyzed levels of CD27 and CD70 in 153 ESCC patients and found that m RNA levels of both CD27 and CD70 in ESCC tissues were significantly lower than those in para-cancer normal tissues(P < 0.0043 and P < 0.0029;)..Our kaplan-meier curve and log-rank tests showed that both CD27 and CD70 expression were significantly associated with better overall survival in ESCC patients(P = 0.0027 and P = 0.045).Next,we determined the correlation between CD27 and CD70 expression and clinicopathological parameters in our patients,and found that CD27 expression was negatively correlated with tumor stage T and stage N,while CD70 expression was negatively correlated with tumor stage N.Since proteins are the functional units of any protein-coding gene,we used immunohistochemistry to detect the expression of CD27 and CD70 proteins in 126 pairs of surgical tissue samples from ESCC patients.We divided the patients into low CD27 expression tumors and high CD27 expression tumors and low CD70 expression tumors and high CD70 expression tumors.We found that the expression of CD27 and CD70 proteins in ESCC tissues was significantly lower than that in normal esophageal tissues(P < 0.0001 and P < 0.05).In addition,CD27 and CD70 expression was significantly associated with overall survival(P = 0.0071 and P = 0.0022).3.Relationship between CD27 and CD70 and other cytokines CD27 expression was significantly correlated with levels of CD8 A,GZMB,IFNG,CD8+ T cell recruitment related chemoattractants(CXCL9,CXCL10,and CXCL11)and CD8 receptors(CCR5,CXCR6,and CXCR3),while CD70 expression was negatively correlated with levels of immunosuppression checkpoints(pd-l1,pd-l2,and HHLA2).Conclusions These data suggest that detection of CD70/CD27 may be a biomarker for ESCC early detection and prognosis prediction.