L-选择素及其配体足萼糖蛋白在结肠癌发生、发展中的表达和意义

Expression and Significance of L⁃Selectin and its Ligand Podocalyxin in Development and Progression of Colon Cancer

背景:结肠癌的早期诊治能有效改善患者的预后,简单有效且敏感的筛查指标对及早识别早期癌症及其癌前病变具有重要意义。L⁃选择素是细胞黏附分子,足萼糖蛋白(PODXL)是其配体,两者在癌症的发生、发展中发挥关键作用。目的:探讨L⁃选择素及其配体PODXL在结肠癌中的表达和意义。方法:收集2020年11月—2022年11月杭州市临安区第一人民医院和浙江中医药大学附属第一医院的病理标本120例(增生性息肉、结肠腺瘤、结肠癌各40例),另取正常肠黏膜组织20例作为对照。采用qRT⁃PCR和免疫组化法分别检测L⁃选择素、PODXL mRNA和蛋白表达。采用蛋白质印迹法测定L⁃选择素和PODXL蛋白表达,并分析其与结肠癌临床病理参数的关系。此外,收集60例结肠癌患者血清标本。以ELISA法检测血清L⁃选择素和PODXL浓度。结果:结肠腺瘤组L⁃选择素和PODXL mRNA和蛋白表达明显高于正常对照组、增生性息肉组(P<0.05),而结肠癌组又显著高于正常对照组、增生性息肉组和结肠腺瘤组(P<0.05)。不同病理类型、淋巴结转移、Dukes分期的结肠癌患者中L⁃选择素和PODXL蛋白表达相比差异有统计学意义(P<0.05)。结肠癌组织中L⁃选择素表达与PODXL表达具有显著正相关性(r=0.855,P<0.001)。初发组血清L⁃选择素和PODXL浓度显著低于复发组,未转移组亦显著低于转移组(P<0.05)。术后3个月血清L⁃选择素和PODXL浓度显著低于术后3 d和术前(P<0.05)。结论:L⁃选择素和PODXL可能参与了结肠癌发生、发展的病理过程,属于致癌蛋白,可为结肠癌的预防和早期诊治提供参考价值,通过早期筛查病变可在一定程度上改善结肠癌患者的预后。

Background:Early diagnosis and treatment can effectively improve the prognosis of colon cancer.Simple,effective and sensitive screening indicators are of great significance for identification of early cancer and precancerous lesions.L⁃selectin is a cell adhesion molecule,and podocalyxin(PODXL)is its ligand,both of them play key roles in the development of cancer.Aims:To investigate the expression and significance of L⁃selectin and its ligand PODXL in colon cancer.Methods:A total of 120 cases of pathological specimens(40 hyperplastic polyp,40 colon adenoma,and 40 colon cancer)from Nov.2020 to Nov.2022 at the Frist People′s Hospital of Hangzhou Lin′an District and the First Affiliated Hospital of Zhejiang Chinese Medical University were collected,and 20 cases of normal intestinal mucosal tissue were served as controls.qRT⁃PCR and immunohistochemistry were used to detect the mRNA and protein expressions of L⁃selectin and PODXL,respectively.Western blotting was used to determine the expressions of L⁃selectin and PODXL,and their relations with different clinicopathological parameters of colon cancer were analyzed.In addition,60 serum specimens of colon cancer were collected.ELISA was used to detect serum concentrations of L⁃selectin and PODXL.Results:Expressions of L⁃selectin and PODXL mRNA and protein in colon adenoma group were significantly higher than those in normal controls and hyperplastic polyp group(P<0.05),and mRNA and protein expressions of L⁃selectin and PODXL in colon cancer group were significantly higher than those in normal controls,hyperplastic polyp group and colon adenoma group(P<0.05).Significant differences in protein expressions of L⁃selectin and PODXL were found in different pathological types,lymph node metastasis,Dukes staging in colon cancer(P<0.05).Expression of L⁃selectin was positive correlated with expression of PODXL in colon cancer(r=0.855,P<0.001).Serum concentrations of L⁃selectin and PODXL were significantly lower in the initial group than in the relapse group(P<0.05),and serum concentrations of L⁃selection and PODXL was significantly lower in the non⁃metastatic group than in the metastatic group(P<0.05).Serum concentrations of L⁃selectin and PODXL at 3 months after surgery was significantly lower than 3 days after surgery and before surgery(P<0.05).Conclusions:L⁃selectin and PODXL may be involved in the development and progression of colon cancer.They are carcinogenic proteins,and their detection could provide reference value for the prevention and early diagnosis of colon cancer,and through early screening of lesion could improve the prognosis of colon cancer to a certain extent.