GUCY2C在结直肠癌中的表达水平及靶向治疗的临床价值分析  

Expression and clinical significance of GUCY2C in colorectal cancer:implications for targeted therapy

作　　者：刘路[1] 郭凤华 郭金玲 墨玉娜 张旭磊[1] 李丹 Liu Lu;Guo Fenghua;Guo Jinling;Mo Yuna;Zhang Xulei;Li Dan(Department of Gastroenterology,The Seventh People’s Hospital of Hebei Province,Dingzhou 073000,Hebei,China;Department of Pathology,The Seventh People’s Hospital of Hebei Province,Dingzhou 073000,Hebei,China;Department of Spleen and Stomach Diseases,The Seventh People’s Hospital of Hebei Province,Dingzhou 073000,Hebei,China)

机构地区：[1]河北省第七人民医院消化内镜科,河北定州073000 [2]河北省第七人民医院病理科,河北定州073000 [3]河北省第七人民医院脾胃病科,河北定州073000

出　　处：《结直肠肛门外科》2025年第1期55-60,共6页Journal of Colorectal & Anal Surgery

摘　　要：目的检测鸟苷酸环化酶C(GUCY2C)在结直肠癌组织中的表达,分析GUCY2C对患者临床病理特征和生存率的影响及靶向GUCY2C治疗结直肠癌的潜在价值。方法收集2018年12月至2020年12月行结直肠癌根治术治疗的152例患者的组织标本及临床资料。通过免疫组化实验检测GUCY2C在结直肠癌及癌旁组织(距离癌组织>3 cm)中的表达情况,分析结直肠癌组织中GUCY2C的表达与临床病理特征及预后的关系。采用转染技术敲低HCT116细胞中GUCY2C的表达,设置对照组(con-GUCY2C组)和GUCY2C敲低组(si-GUCY2C组),采用细胞增殖实验和侵袭实验分别检测敲低GUCY2C的表达后对HCT116细胞的增殖和侵袭的影响。结果免疫组化结果显示,GUCY2C在结直肠癌组织中的阳性表达率高于癌旁组织(P<0.001)。结直肠癌组织中GUCY2C的表达与肿瘤分化程度、淋巴结转移、肿瘤远处转移和肿瘤TNM分期有关(P<0.05)。GUCY2C(-)、GUCY2C(+)、GUCY2C(++)和GUCY2C(+++)患者术后3年总生存率、3年无病生存率比较差异有统计学意义(P<0.05)。si-GUCY2C组GUCY2C蛋白相对表达水平、细胞培养72 h后的光密度值及穿膜细胞数均低于con-GUCY2C组,差异有统计学意义(P<0.001)。结论GUCY2C阳性表达强度与结直肠癌浸润和转移相关并影响患者生存率,敲低GUCY2C的表达可降低细胞的增殖和侵袭能力,靶向GUCY2C治疗CRC有望成为新的治疗方向。Objectives To detect the expression of guanylyl cyclase 2C(GUCY2C)in colorectal cancer(CRC)tissues and analyze its impact on clinicopathological features,survival rates,and the potential value of GUCY2C-targeted therapy.Methods Tissue specimens and clinical data from 152 patients undergoing radical CRC resection between December 2018 and December 2020 were collected.Immunohistochemistry(IHC)was used to assess GUCY2C expression in CRC tissues and adjacent non-cancerous tissues(>3 cm from the tumor).The correlation between GUCY2C expression and clinicopathological features or prognosis was analyzed.GUCY2C expression was knocked down in HCT116 cells via transfection,with cells divided into control(con-GUCY2C)and knockdown(si-GUCY2C)groups.Cell proliferation and invasion assays were performed to evaluate functional changes.Results IHC revealed a significantly higher positive expression rate of GUCY2C in CRC tissues than in adjacent tissues(P<0.001).GUCY2C expression correlated with tumor differentiation degree,lymph node metastasis,distant metastasis,and tumor node metastasis stage(P<0.05).Significant differences in 3-year overall survival and disease-free survival rates were observed among patients with GUCY2C expression levels of(-),(+),(++),and(+++)(P<0.05).The si-GUCY2C group exhibited lower GUCY2C protein levels,optical density values(72-hour culture),and transmembrane cell counts compared to the con-GUCY2C group(P<0.001).Conclusion GUCY2C expression intensity correlates with CRC invasion,metastasis,and survival outcomes.Knockdown of GUCY2C suppresses cellular proliferation and invasion,suggesting that GUCY2C-targeted therapy may represent a novel therapeutic strategy for CRC.

关 键 词：结直肠癌 鸟苷酸环化酶C 增殖 侵袭 

分 类 号：R735.3[医药卫生—肿瘤]