MMP3、LCN2及DCN在结直肠腺瘤性息肉及结直肠癌中的表达及意义  

The expression and significance of MMP3,LCN2,and DCN in colorectal adenomatous polyps and colorectal cancer

作　　者：王瑾 李越洋 王宇 王立哲 杜嘉慧 曹永一[2] 李宗伟 朱婷[2] WANG Jin;LI Yueyang;WANG Yu;WANG Lizhe;DU Jiahui;CAO Yongyi;LI Zongwei;ZHU Ting(Bengbu Medical University,Bengbu,Anhui 233030,China;Department of Oncology,Hefei First People′s Hospital,Hefei,Anhui 230071 China;College of Life Sciences,Anhui Medical University,Hefei,Anhui 230032,China)

机构地区：[1]蚌埠医科大学,233030 [2]合肥市第一人民医院肿瘤科,230071 [3]安徽医科大学生命科学学院,230032

出　　处：《现代消化及介入诊疗》2024年第12期1419-1425,共7页Modern Interventional Diagnosis and Treatment in Gastroenterology

基　　金：国家自然科学基金(82270217);合肥市应用医学项目(Hwk2023zd021);2023年安徽医科大学校科研基金项目(2023xkj110);安徽省中医药传承创新科研项目(2024CCCX147)。

摘　　要：目的 探讨结直肠癌发生发展的关键基因,分析关键基因的表达水平与结直肠癌患者的临床病理特征及预后的相关性。方法 通过GEO2R、Metascape数据库及String数据库筛选出与结直肠癌发生发展相关的关键基因。选取2019年1—12月合肥市第一人民医院同时获取到结直肠腺瘤性息肉、结直肠癌和癌旁正常组织标本的30例患者,采用免疫组化检测患者标本中MMP3、LCN2、DCN的表达水平;分析MMP3、LCN2、DCN的表达水平与结直肠癌患者的临床特征的关系;绘制Kaplan-Meier生存曲线,比较三种基因的表达水平与结直肠癌患者五年PFS和OS的关系。结果 通过筛选选取MMP3、LCN2及DCN作为本次研究的关键基因;结直肠癌及腺瘤性息肉的病理标本中MMP3(χ^(2)=6.929,P<0.05)和LCN2(χ^(2)=10.396,P<0.05)的表达水平显著高于癌旁正常组织,且以结直肠癌标本最为显著,而DCN在癌旁正常组织、腺瘤性息肉、结直肠癌中的表达逐渐下降(χ^(2)=19.474,P<0.05);MMP3的表达水平与结直肠癌患者的CEA值、微卫星不稳定性以及有无远处转移相关(P<0.05);而LCN2和DCN的表达水平都仅与是否远处转移相关(P<0.05);Kaplan-Meier生存曲线结果表明,LCN2及DCN的表达水平与五年PFS相关(P=0.010,P=0.008);MMP3、LCN2和DCN的表达水平都与结直肠癌患者的OS相关(P=0.003,P=0.003,P=0.014)。结论 MMP3、LCN2及DCN可能与腺瘤-癌的发生发展存在一定联系,且表达水平与CRC患者的预后相关,对未来CRC的早发现、早诊断及早治疗可提供一定的思路。Objective To investigate the key genes involved in the development and progression of colorectal cancer(CRC) and analyze the correlation between their expression levels and the clinicopathological characteristics and prognosis of CRC patients.Methods Key genes associated with the development and progression of CRC were identified using the GEO2R,Metascape,and STRING databases.A total of 30 patients treated at Hefei First People′s Hospital from January to December 2019 were selected.Specimens of colorectal adenomatous polyps,CRC tissues,and adjacent normal tissues were collected from these patients.The expression levels of MMP3,LCN2,and DCN in these specimens were detected using immunohistochemistry.The relationship between the expression levels of these genes and the clinical characteristics of CRC patients was analyzed.Kaplan-Meier survival curves were drawn to compare the associations of these genes′ expression levels with five-year progression-free survival(PFS) and overall survival(OS).Results MMP3,LCN2,and DCN were identified as key genes in this study.The expression levels of MMP3 and LCN2 were significantly higher in colorectal adenomatous polyps and CRC tissues compared to adjacent normal tissues,with the highest expression observed in CRC tissues.Conversely,DCN expression decreased progressively in adjacent normal tissues,adenomatous polyps,and CRC tissues.MMP3 expression was significantly associated with CEA levels,microsatellite instability,and distant metastasis in CRC patients(P<0.05).The expression levels of LCN2 and DCN were only associated with distant metastasis(P<0.05).Kaplan-Meier survival curve analysis showed that LCN2 and DCN expression levels were correlated with five-year PFS(P=0.010,P=0.008),while MMP3,LCN2,and DCN expression levels were all associated with OS(P=0.003,P=0.003,P=0.014).Conclusion MMP3,LCN2,and DCN may play roles in the adenoma-carcinoma sequence and are associated with the prognosis of CRC patients.These findings may provide insights into the early detection,diagnosis,

关 键 词：腺瘤性息肉 结直肠癌 差异表达基因 预后 MMP3 LCN2 DCN 

分 类 号：R714.255[医药卫生—妇产科学] R574[医药卫生—临床医学]