The Effect Of COPS5 On The Prognosis Of Patients With Esophageal Squamous Cell Carcinoma And Its Mechanism

Background and purpose:Esophageal squamous cell carcinoma(esophageal squamous cell carcinoma)is one of the most deadly gastrointestinal malignant tumors in the world today.Because of its insidious onset,the early symptoms are mostly insignificant,and the metastasis generally appears earlier,the patient is often in the advanced stage once the disease is discovered.And because the anatomical position of the esophagus is located inside the mediastinum,the surrounding of the lesion is often adjacent to the important tissue structures such as the large vessels of the heart,which brings great difficulties to the treatment and also leads to a general poor prognosis of the patient.In the treatment of esophageal squamous cell carcinoma,for patients with surgical indications and good general condition,surgical treatment is one of the preferred treatments recommended by the diagnosis and treatment guidelines.After the operation,based on the results of pathological diagnosis combined with the TNM staging method developed by WHO,the patient’s tumor progression is comprehensively evaluated by integrating the depth of the patient’s primary tumor invasion,lymph node metastasis,and the presence of distant metastasis.To provide further guidance on the follow-up adjuvant treatment plan.However,although TNM staging is currently the internationally recognized standard for tumor staging,we still find in clinical practice that the judgment of the condition based on TNM staging sometimes lacks sufficient flexibility.With the development of molecular biology technology today,people’s understanding of cancer has gradually deepened from the traditional histological and pathological levels to the molecular and genetic levels.Therefore,combined with the latest scientific research progress,it is necessary to further improve the therapeutic effect of esophageal squamous cell carcinoma and further improve the prognosis of patients with comprehensive analysis of cancer at the molecular and genetic levels and accurate staging of the patient’s condition.However,for the disease of esophageal squamous cell carcinoma,research in this area is still insufficient.The scientific community has not yet proposed a reliable and recognized molecular biological marker for the prognosis of patients with esophageal squamous cell carcinoma.COPS5(also known as CSN5,JAB1)is a multifunctional protein that can regulate cell function.It was previously thought to play an important role in the occurrence,progression,and metastasis of various cancers.However,the current research on the role and mechanism of COPS5 in esophageal squamous cell carcinoma is still insufficient,and there are still few reports on relevant researches in this direction.The purpose of this study was to investigate the expression of COPS5 in human esophageal squamous cell carcinoma tissues,combined with the patient’s pathological characteristics and clinical data obtained from clinical follow-up,analyze the clinical factors affecting the expression of COPS5,explore the expression level of COPS5 and the operation of patients with esophageal squamous cell carcinoma Association between post-prognosis.Further cell transfection and design of cell function and nude mice xenograft experiments were conducted to study the effect of COPS5 on the malignant behavior of esophageal squamous carcinoma cellsMethods:Immunohistochemical staining(IHC)and Western blotting(Western-blot)were used to detect the expression of COPS5 in tumor tissues of patients with esophageal squamous cell carcinoma.Based on the clinical information obtained from clinical follow-up,SPSS22.0 software was used to establish an information database and further analysis.First,the chi-square test was used to analyze the relationship between the expression of COPS5 and various clinicopathological characteristics of the patients.The Kaplan-meier method was further used to analyze the influence of single factors and multi-factors on the prognosis of patients.The log-rank test was used to judge the different factors for patients.Whether there is a difference in the impact of survival rate at the time.Transfected esophageal squamous carcinoma cell lines with synthetic COPS5 overexpressing lentivirus and small interfering RNA respectively,constructed COPS5 overexpressed and underexpressed esophageal squamous carcinoma cell lines,and designed cell function experiments and nude mouse xenograft experiments To explore the effect of COPS5 expression on malignant behaviors such as proliferation,migration and invasion of esophageal squamous cell carcinomaResults:A total of 124 patients with esophageal squamous cell carcinoma who underwent Ivor-Lewis operation were included in this experiment.According to the tumor tissue immunohistochemical staining results,it was classified into high expression group(65 cases,52.4%)and low expression group(59 cases,47.5%).Western blot analysis of tissue proteins showed that COPS5 had a higher expression level in esophageal squamous cell carcinoma compared with adjacent tissues.This result was statistically significant(P<0.01).Further combining with the clinical data of the patients,the analysis of univariate and multivariate clinical data shows that patients with COPS5 overexpression in tumor tissue have a poor prognosis.Corresponding cell function experiments found that the up-regulation of COPS5 in esophageal squamous carcinoma cell lines can enhance the proliferation,migration,and invasion ability of cancer cells,but showed the opposite effect in the down-regulated COPS5 group.Xenograft tumor experiments in nude mice confirmed that COPS5 overexpressed tumors grew faster than the control group.Conclusion:COPS5 is widely overexpressed in the tumor tissue of patients with esophageal squamous cell carcinoma,and this overexpression effect can promote the proliferation,migration and invasion of esophageal squamous cell carcinoma cells,which is obviously related to the poor prognosis of patients.COPS5 may play an important role in the occurrence and progression of esophageal squamous cell carcinoma,and it is a promising predictor of prognosis and a potential targeted therapy target.