Expression Of USP15 In Esophageal Squamous Cell Carcinoma And Its Association With Clinicopathological Features

Background:The incidence of esophageal cancer(EC)shows significant regional differentiation,as one of the high incidence areas of esophageal cancer in China,its incidence rate and mortality rate are ranked 5th and 4th among all malignant tumors,and the 5-year survival rate is only about 20%,which poses a great threat to the health and quality of life of the population.In China,more than 90%of esophageal cancers are the histological subtype of esophageal squamous cell carcinoma(ESCC).However,the specific mechanism of the onset and progression of esophageal squamous cell carcinoma in the current study is not clear,and there is a lack of a reasonable and complete scheme for the screening,diagnosis and treatment of ESCC,as well as recurrent metastasis and prognosis judgment.Therefore,it is important to look for new molecular markers for the diagnosis and treatment of ESCC and provide indicators that can assess tumor migration and prognostic risk.Ubiquitin-Specific Protease 15(USP15)has been found to play a carcinogenic role in a variety of malignancies,and is associated with poor prognosis in patients,and may become a new therapeutic target for malignant tumors.However,the expression of USP15 in ESCC tissues and its correlation with the clinicopathological parameters and prognosis of patients have not been reported.Objective:To study the expression of USP15 in normal esophageal squamous epithelium and ESCC tissues and analyze its correlation with the clinicopathological features of patients.Methods:Esophageal squamous cell carcinoma paraffin samples undergoing radical resection in Taizhou People’s Hospital were collected,and paraffin samples of paracancerous esophageal tissue were collected at the same time,and the operation time was limited to January 01,2018 to December 31,2019.Among them,there were 156cases of ESCC organization and 72 cases of normal esophageal tissue.All patients included in the experiment were pathologically confirmed.Tissue chips were prepared and immunohistochemical(Envision)staining was performed,and the films were read independently by two experienced and highly qualified pathologists when all clinical pathological parameters were unknown,and the final results were displayed semi-quantitatively,that is,the proportion of positive cells and staining intensity were reported at the same time.The final score for each slice was calculated according to the same scoring criteria and divided into a high expression group(≥6 points)and a low expression group(<6 points).The experimental data were collated and analyzed using SPSS 26.0 software.Results:1.USP15 was not expressed in normal esophageal squamous epithelium or was only weakly positively expressed in focal basal cells,and was positively expressed in ESCC tissues,with positive rates of 26.4%(19/72)and 86.5%(135/156),respectively,with statistically significant differences(χ~2=81.303,P<0.001).The expression level of USP15 in ESCC tissues was independent of the patient’s sex,age,cancer size,general classification,expression of Cyclin D1 and expression of P53(P>0.05),but was not related to tumor growth site(χ~2=6.806,P=0.033),histological grade(χ~2=29.771,P<0.001),depth of invasion(χ~2=8.386,P=0.004),lymph node metastasis(χ~2=4.209,P=0.040),nerve invasion(χ~2=5.596,P=0.018),Ki-67 proliferation index(χ~2=5.632,P=0.018),and clinical stage(χ~2=15.498,P<0.001)were closely related.2.Spearman correlation analysis showed that the expression of USP15 in ESCC tissues and lymph node metastases was positively correlated(r=0.531,P=0.001).The Kaplan-Meier survival curve showed that USP15 high expressors had a worse prognosis than low expressioners(Log Rank testχ~2=9.164,P=0.002).3.Univariate Cox regression analysis showed that tumor maximum diameter(HR=2.016,95%CI=1.150-3.535,P=0.014),degree of differentiation(HR=2.529,95%CI=1.444-4.429,P=0.001),depth of invasion(HR=2.221,95%CI=1.202-4.102,P=0.011),lymph node metastasis(HR=3.091,95%CI=1.114-8.579,P=0.030),neuroaggression(HR=2.243,95%CI=1.176-4.278,P=0.014),USP15 expression level(HR=2.868,95%CI=1.395-5.898,P=0.004),clinical stage(HR=2.702,95%CI=1.460-5.000,P=0.002),and postoperative treatment(HR=0.528,95%CI=0.285-0.977,P=0.042)may be a risk factor for prognosis in patients with ESCC.Incorporating the above variables into multivariate Cox regression analysis showed that tumor maximum diameter(HR=1.786,95%CI=1.002-3.183,P=0.049),degree of tissue differentiation(HR=2.017,95%CI=1.071-3.799,P=0.030),presence or absence of lymph node metastasis(HR=4.402,95%CI=1.146-16.908,P=0.031),and postoperative treatment(HR=0.471,95%CI=0.251-0.883,P=0.019),is an independent prognostic risk indicator for patients with ESCC.Conclusions:1.The expression of USP15 in ESCC tissues was significantly upregulated,indicating that USP15 plays a role in the occurrence and development of ESCC as a carcinogen.2.The expression of USP15 is closely related to Ki-67,indicating that USP15 may promote ESCC progression by promoting tumor cell proliferation.3.The expression of USP15 in ESCC tissue and lymph node metastases was positively correlated,indicating that USP15 may promote ESCC progression by promoting tumor cell migration.4.The expression of USP15 is related to the prognosis of ESCC patients,and the prognosis of patients with high expression of USP15 is worse.Therefore,USP15 is expected to be used as a new therapeutic target and prognostic evaluation index for ESCC.