非小细胞肺癌中Cbl家族表达与临床病理及预后的关系

Expression of Cbl family in non-small cell lung cancer and its relationship with clinicopathology and prognosis

目的检测非小细胞肺癌(NSCLC)中E3泛素连接酶Cbl家族c-Cbl、Cbl-b、Cbl-c蛋白表达水平,并分析其与临床病理、预后的关系。方法本研究为前瞻性研究。选取2020年1月至2023年1月在汉中市人民医院治疗的NSCLC患者102例作为研究对象,其中男78例、女24例,年龄(67.49±8.33)岁。选取手术切除的癌旁组织作为对照。免疫组织化学染色法检测癌组织、癌旁组织c-Cbl、Cbl-b、Cbl-c蛋白表达。收集患者临床病理特征(性别、年龄、吸烟史、病灶位置、TNM分期、组织分化程度、病理类型、胸膜侵袭),并对比患者癌组织c-Cbl、Cbl-b、Cbl-c蛋白表达;用Cox回归模型分析NSCLC预后的影响因素。绘制Kaplan-Meier曲线分析癌组织Cbl-b、Cbl-c蛋白表达与NSCLC预后的关系。统计学方法采用t检验、χ^(2)检验。结果癌组织c-Cbl、Cbl-b、Cbl-c蛋白表达阳性率均高于癌旁组织[52.94%(54/102)比37.25%(38/102)、63.73%(65/102)比43.14%(44/102)、67.65%(69/102)比39.22%(40/102)],差异均有统计学意义(χ^(2)=5.068、8.688、16.568,均P<0.05)。有吸烟史、TNM分期Ⅲ期、未/低分化、胸膜侵袭患者癌组织c-Cbl、Cbl-b、Cbl-c蛋白表达均高于无吸烟史、TNM分期Ⅰ/Ⅱ期、中/高分化、无胸膜侵袭患者[吸烟史:62.32%(43/69)比33.33%(11/33)、73.91%(51/69)比42.42%(14/33)、78.26%(54/69)比45.45%(15/33);TNM分期:76.00%(19/25)比45.45%(35/77)、88.00%(22/25)比55.84%(43/77)、92.00%(23/25)比59.74%(46/77);组织分化程度:65.22%(30/46)比42.86%(24/56)、78.26%(36/46)比51.79%(29/56)、82.61%(38/46)比55.36%(31/56);胸膜侵袭:80.00%(20/25)比44.16%(34/77)、88.00%(22/25)比55.84%(43/77)、92.00%(23/25)比59.74%(46/77)],差异均有统计学意义(χ^(2)=7.528、9.575、10.978、7.068、8.442、8.974、5.068、7.658、8.570、9.733、8.442、8.974,均P<0.05)。Cox回归分析显示,吸烟史、TNM分期Ⅲ期、未/低分化、胸膜侵袭、癌组织Cbl-b蛋白表达、癌组织Cbl-c蛋白表达是NSCLC患者预后的影响因素(均P<0.05)。Cbl-b阳性组无进展生存时间为27个月(95%CI 22.602~31.398),Cbl-b阴性组无进展生存时间为40个月(95%CI 28.810~51.190),Kaplan-Meier生存曲线总体比较,差异有统计学意义(χ^(2)=6.709,P=0.010);Cbl-c阳性组无进展生存时间为28 个月(95%CI 23.786~32.214),Cbl-c 阴性组无进展生存时间为39 个月(95%CI 29.892~48.108),Kaplan-Meier生存曲线总体比较,差异有统计学意义(χ^(2)=4.605,P=0.032)。结论 NSCLC中c-Cbl、Cbl-b、Cbl-c蛋白高表达,三者均与吸烟史、TNM分期、分化程度及胸膜侵袭相关,其中Cbl-b、Cbl-c是NSCLC预后的影响因素。

Objective To detect the expression levels of Cbl-b,c-Cbl,and Cbl-c proteins of E3 ubiquitin ligase casitas b-lineage lymphoma(Cbl)family in non-small cell lung cancer(NSCLC),and to analyze their relationship with clinicopathological features and prognosis.Methods This was a prospective study.A total of 102 patients with NSCLC admitted to Hanzhong People's Hospital from January 2020 to January 2023 were selected,including 78 males and 24 females.They were(67.49±8.33)years old.The cancer-adjacent tissues removed by surgery were used as controls.The immunohistochemical staining was used to detect the expressions of Cbl-b,c-Cbl,and Cbl-c proteins in the cancer tissues and cancer-adjacent tissues.The expressions of Cbl-b,c-Cbl,and Cbl-c proteins in the cancer tissues of the patients with different clinicopathological characteristics(gender,age,smoking history,lesion site,TNM stage,differentiation grade,pathological type,and pleural invasion)were compared.The Cox regression model was used to analyze the influencing factors of the patients'prognosis.Kaplan-Meier curves were drawn to analyze the relationship between the expressions of Cbl-b and Cbl-c proteins in the cancer tissues and NSCLC prognosis.t andχ^(2) tests were applied.Results The positive expression rates of Cbl-b,c-Cbl,and Cbl-c proteins in the cancer tissues were higher than those in the cancer-adjacent tissues[52.94%(54/102)vs.37.25%(38/102),63.73%(65/102)vs.43.14%(44/102),and 67.65%(69/102)vs.39.22%(40/102)],with statistical differences(χ^(2)=5.068,8.688,and 16.568;all P<0.05).The positive expression rates of Cbl-b,c-Cbl,and Cbl-c proteins in the cancer tissues of the patients with smoking history,TNM stageⅢ/Ⅳ,undifferentiated/low differentiation,and pleural invasion were higher than those of the patients without smoking history and with TNM stage I/Ⅱ,moderate/high differentiation,and no pleural invasion[smoking history:62.32%(43/69)vs.33.33%(11/33),73.91%(51/69)vs.42.42%(14/33),and 78.26%(54/69)vs.45.45%(15/33);TNM stage:76.00%(19/25)vs.45.45%(35/77),88.00%(22/25)vs.55.84%(43/77),and 92.00%(23/25)vs.59.74%(46/77);differentiation:65.22%(30/46)vs.42.86%(24/56),78.26%(36/46)vs.51.79%(29/56),and 82.61%(38/46)vs.55.36%(31/56);pleural invasion:80.00%(20/25)vs.44.16%(34/77),88.00%(22/25)vs.55.84%(43/77),and 92.00%(23/25)vs.59.74%(46/77)],with statistical differences(χ^(2)=7.528,9.575,10.978,7.068,8.442,8.974,5.068,7.658,8.570,9.733,8.442,and 8.974;all P<0.05).The Cox regression analysis showed that smoking history,TNM stageⅢ,undifferentiated/low differentiation,pleural invasion,and Cbl-b protein expression and Cbl-c protein expression in the cancer tissues were the influencing factors of the patients'prognosis(all P<0.05).The progression-free survival time of the Cbl-b positive group was 27 months(95%CI 22.602-31.398 months),and that of Cbl-b negative group was 40 months(95%CI 28.810-51.190 months);the overall comparison of Kaplan-Meier survival curves showed a statistical difference(χ^(2)=6.709,P=0.010).The progression-free survival time of the Cbl-c positive group was 28 months(95%CI 23.786-32.214 months),and that of the Cbl-c negative group was 39 months(95%CI 29.892-48.108 months);the overall comparison of Kaplan-Meier survival curves showed a statistical difference(χ^(2)=4.605,P=0.032).Conclusions Cbl-b,c-Cbl,and Cbl-c proteins are highly expressed in NSCLC.All the three are related to smoking history,TNM stage,differentiation degree,and pleural invasion.Among them,Cbl-b and Cbl-c are influencing factors of prognosis of patients with NSCLC.