LAMA4 In Esophageal Squamous Cell Carcinoma And Its Relationship With Clinicopathologic Features

BackgroundEsophageal cancer(EC)is a malignant tumour with no specific symptoms in the early stage,aggressive disease,poor prognosis and short survival period,and the incidence of the disease is getting younger every year,posing a severe threat to human health.In China,oesophageal cancer ranks 6th in cancer incidence and 4th in cancer mortality,both higher than the global average incidence level(7th)and mortality level(6th).The two main pathological types of oesophagal cancer are Esophageal Squamous Cell Carcinoma(ESCC)and Esophageal Adenocarcinoma(EAC),of which ESCC is the predominant one.There are significant differences in their biological characteristics and epidemiological distribution features.In some parts of northern China,ESCC can exceed90%,with an overall 5-year survival rate of less than 30%.Therefore,it is of great significance to explore the process of oesophagal carcinogenesis,development,related influencing factors and mechanisms for the prevention,early detection,early treatment and improvement of the prognosis of ESCC.The Tumor Microenvironment(TME)is the cradle of malignant tumour survival.It adapts to the tumour cells and promotes their growth and metastasis by regulating and modifying the microenvironment.Laminin alpha4(LAMA4)is one of the critical components of the tumour microenvironment.It is mainly found in the endothelial basement membrane and mesenchyme,has an endothelial-specific expression pattern and promotes angiogenesis,and plays an important role in promoting the survival,proliferation and migration of various cell types.However,several studies have shown that LAMA4 is involved in the development and metastasis of various malignancies and can induce tumour resistance,infiltration of some immune cells for treatment and other effects primarily associated with poor prognosis of patients.However,its expression in ESCC and its role and mechanism in the development and progression of ESCC is unknown.ObjectiveThis study aimed to investigate the expression of LAMA4 protein in normal oesophagal squamous epithelial tissue,oesophagal intraepithelial neoplastic tissue and oesophagal squamous cell carcinoma tissue to explore the expression of LAMA4 protein in ESCC,its expression correlation with the clinicopathological characteristics and prognosis of ESCC.MethodsOne hundred and forty-nine specimens of patients who underwent radical oesophagal cancer surgery from January 2018 to December 2019 with complete clinicopathological data were selected from the case bank of Tai Zhou People’s Hospital,50 cases of high-grade intraepithelial neoplasia of the oesophagus from oesophagal EMR or ESD and 50 cases of low-grade intraepithelial neoplasia of the oesophagus were taken during the same period,and 91 cases of normal oesophagal squamous epithelial tissue adjacent to the cancer were taken as usual All patients are diagnosed by pathology.All patients are diagnosed by pathology.LAMA4 protein expression was measured in each group by the tissue chip technology and immunohistochemistry En Vision method,and its relationship with clinicopathological features and prognosis was analyzed.Results1.The favourable expression rates of LAMA4 protein in normal oesophagal squamous epithelium,oesophagal intraepithelial neoplasia(LGIN+HGIN),and oesophagal squamous cell carcinoma were 3.3%(3/91),17.0%(17/100),and 55.7%(83/149),respectively,with statistically significant differences between groups(P<0.05).2.In oesophagal squamous cell carcinoma,the expression level of LAMA4 strongly correlates with the sarcoid type,size,differentiation,presence of lymph node metastasis,Ki-67 expression and tumour stage of ESCC patients(P<0.05).At the same time,there was no significant difference between it and patients’ age,gender,tumour site,infiltration depth,vascular invasion,and nerve invasion(P>0.05).There was no significant difference with the Immunohistochemical markers P53,EGFR and Cyclin D1(P>0.05).3.The positive rate of vascular expression of LAMA4 in oesophagal tumour cells tumour was 87.9%(131/149),the positive rate of vascular expression of LAMA4 protein in oesophagal intraepithelial neoplasia(LGIN+HGIN)tissue was 7%(7/100).In contrast,in 91 cases of normal oesophagal squamous epithelial tissue adjacent to cancer,the positive rate of LAMA4 expression in blood vessels was 1.1%(1/91).All differences between groups were statistically significant(P<0.05).4.The expression of LAMA4 in cancer tissues significantly correlates with the expression of TEM8.Kaplan-Meier survival analysis showed that the prognosis of the group with high LAMA4 expression was significantly lower than that of the group with low LAMA4 expression(P<0.05),and the prognosis of the group with positive TEM8 expression was significantly lower than that of the group with negative TEM8 expression(P<0.05).Conclusion:1.LAMA4 expression was upregulated in oesophagal squamous cell carcinoma tissues and patients with high LAMA4 expression had a worse prognosis compared with those in the low LAMA4 expression group.It hypothesises that LAMA4 may be involved in the invasive growth of ESCC and the progression of clinical course,providing a reliable experimental basis for further study of the factors and molecular mechanisms influencing the occurrence,development and metastasis of oesophagal squamous cell carcinoma.2.The expression of LAMA4 is upregulating in the intra-tumoral vessels of oesophagal squamous cell carcinoma comparing to expression of LAMA4 protein in oesophagal intraepithelial neoplasia(LGIN+HGIN)tissue and normal oesophagal squamous epithelial tissue,which could use as a late-stage marker and potential therapeutic target for oesophagal squamous cell carcinoma.