The Expression Of UCH-L1 In Non-small Cell Lung Cancer And Its Correlation With Clinicopathological Features And Prognosis

Background and objectivesLung cancer is not only a common disease,but also one of the highest cancer mortality.Lung cancer can be divided into small cell lung cancer(SCLC)and non-small cell lung cancer(NSCLC).The prognosis of NSCLC is affected by many factors,in addition to histological subtypes,clinical or pathological stages and other factors,treatment strategies and therapeutic effects also have a crucial impact on its prognosis.The expression of some proteins in lung cancer is not only related to the prognosis,but also has targeted therapeutic drugs.Ubiquitin C-terminal hydrolase-L1(UCH-L1)is a kind of cysteine hydrolase.It not only has the function of ubiquitin hydrolase and stabilizing ubiquitin monomer,but also affects cell division through the effect of cell cycle protein deubiquitination.The abnormal expression of UCH-L1 is closely related to the occurrence and development of many tumors.Although some studies in vitro have revealed the significance of UCH-L1 in lung cancer,there are few clinical studies focus on the expression of UCH-L1 in lung cancer at home and abroad;in addition the results are not uniform and controversial.The purpose of this study is to explore the relationship between the expression of UCH-L1 in NSCLC with its clinicopathological characteristics and prognosis,and to explore the significance of the expression of UCH-L1 in NSCLC and whether it can become a potential new target for lung cancer treatment by using immunohistochemistry and clinical information statistics.Materials and methodsIn total,401 cases of NSCLC were collected in the Department of Pathology,The Second Hospital of Jilin University from January 2009 to June 2019.The clinicopathological characteristics and survival data of all cases were collected and analyzed.The expression of UCH-L1 protein in lung cancer tissues was detected by immunohistochemical staining.The relationship between the expression of UCH-L1 protein and the clinicopathological characteristics of the patients was evaluated by statistical method,and the relationship between the expression of UCH-L1 protein and the prognosis of the patients was analyzed.Results1.Among the 401 NSCLC patients,286 were adenocarcinoma(71.3%),51 were squamous cell carcinoma(12.7%)and 64 were others(16.0%).2.In NSCLC,the positive rate of UCH-L1 expression was higher in men than in women(P = 0.001),in smokers than in non-smokers(P < 0.001),and in the tumors with larger size(P = 0.003),in the high pathological stage(P = 0.027),but the positive rate was lower in tumors with infiltration of lymphoid cells than tumors with absent(P =0.035).There was at least one expression of UCH-L1 in cytoplasm or nucleus of male was higher than that of female(P < 0.001);smokers were higher than non-smokers(P < 0.001);the older the patients were,the higher the positive rate was(P = 0.039);the larger the tumor was,the higher the positive rate was(P = 0.002);and the higher the pathological stage was,the higher the positive rate was(P = 0.046).3.In adenocarcinoma,the positive rate of cytoplasmic expression of UCH-L1 with pleura invasion was higher than that without pleura invasion(P = 0.027),and the higher the pathological stage was,the higher the positive rate was(P = 0.027);the positive rate of expression of UCH-L1 in at least one cytoplasm or nucleus was also higher than that without pleura invasion(P = 0.012),and the higher the pathological stage was,the higher the positive rate was(P = 0.043).4.In NSCLC,the cytoplasmic expression of UCH-L1 was related to the shortening of overall survival(OS)(114.55 vs.89.72 months;P = 0.005);the nuclearexpression was related to progression free survival(PFS)(109.99 vs.59.80 months;P< 0.001)and OS(112.88 vs.69.94 months;P < 0.001).At least one expression in cytoplasm or nucleus was related to OS(115.99 vs.87.12 months;P < 0.001).In addition,the expression in nucleus was more significantly related to PFS(110.87,94.07,69.13 vs.37.78 months;P = 0.001)and OS(115.99,90.57,74.13 vs.49.36months;P < 0.001)than that in cytoplasm.5.In adenocarcinoma,the expression of UCH-L1 was related to the shortening of OS(118.55 vs.90.38 months;P = 0.010);the expression of nucleus was related to the shortening of PFS(108.63 vs.29.67 months;P < 0.001)and OS(117.43 vs.41.67months;P < 0.001);at least one expression of cytoplasm or nucleus was related to OS(118.89 vs.89.56 months;P =0.004).In addition,the expression of nucleus was more significantly related to the shortening of PFS(109.53,89.27,31.00 vs.28.33 months;P < 0.001)and OS(118.89,96.21,40.00 vs.43.33 months;P < 0.001)than that of cytoplasm.6.The expression of UCH-L1 in the cytoplasm of NSCLC tumor cells was an independent poor prognostic factor(OS: hazard ratio(HR value)= 1.854;95%confidence interval 1.132-3.038;P = 0.014);the expression of UCH-L1 in the nucleus of NSCLC tumor cells was an independent poor prognostic factor(PFS: HR value =3.169;95% confidence interval 1.578-6.361;P = 0.001;OS: HR value = 3.921;95%confidence interval 1.940-7.925;P < 0.001);at least one expression in the cytoplasm or nucleus of the tumor cell UCH-L1 of NSCLC was an independent poor prognostic factor(OS: HR = 2.282;95% confidence interval 1.418-3.672;P = 0.001).7.The expression of nucleus UCH-L1 in adenocarcinoma cells was an independent poor prognostic factor(PFS: HR = 6.068;95% confidence interval2.308-15.949;P < 0.001;OS: HR = 8.550;95% confidence interval 2.809-26.023;P< 0.001);at least one UCH-L1 expression in the cytoplasm or nucleus of the tumor cell of adenocarcinoma was an independent poor prognostic factor(OS: HR = 2.073;95% confidence interval 1.018-4.221;P = 0.044).Conclusions1.In NSCLC,including adenocarcinoma and squamous cell carcinoma,the expression of UCH-L1 has cytoplasmic expression and a small number of nuclear expression patterns,and the expression of UCH-L1 is different in tumors with different clinicopathological characteristics.The expression of UCH-L1 in NSCLC is positively correlated with age,tumor size and pathological stage.The expression of UCH-L1 in adenocarcinoma is positively correlated with pathological stage,and it is significantly related to pleural infiltration.2.In NSCLC,especially in adenocarcinoma,the expression of UCH-L1 in the cytoplasm and nucleus is related to the poor prognosis(OS and PFS),and its in the nucleus indicates a shorter survival period,which can be used as a prognostic factor for NSCLC patients.