早期结直肠癌内镜黏膜下剥离术标本中PDCD4和自噬相关因子LC3 Ⅱ、p62的表达及其意义  

Expressions and Significance of PDCD4 and Autophagy-related Factors LC3Ⅱ and p62 in Endoscopic Submucosal Dissection Specimens of Early Colorectal Cancer

作　　者：何双[1] 温菲菲 许晓阳 李扬扬[1] 崔忠泽 路丽祯 吴淑华[1] HE Shuang;WEN Feifei;XU Xiaoyang;LI Yangyang;CUI Zhongze;LU Lizhen;WU Shuhua(Department of Pathology,Binzhou Medical University Hospital,Binzhou,Shandong Province 256603)

机构地区：[1]滨州医学院附属医院病理科,256603

出　　处：《胃肠病学》2021年第4期204-211,共8页Chinese Journal of Gastroenterology

基　　金：国家自然科学基金(81772637);滨州医学院科研计划与科研启动基金(BY2015KJ03)。

摘　　要：背景:目前内镜黏膜下剥离术(ESD)已成为早期结直肠癌治疗的首选方法。PDCD4和自噬对结直肠癌的发生具有重要意义。目的:探讨凋亡因子PDCD4和自噬相关因子LC3Ⅱ、p62在结直肠癌中的表达及其临床意义。方法:收集2015年1月—2020年11月滨州医学院附属医院接受ESD治疗的早期结直肠腺癌患者54例,采用免疫组化法检测PDCD4、LC3Ⅱ和p62表达,分析其与患者临床病理特征的关系。利用生物信息学分析PDCD4在泛癌中的表达差异。结果:PDCD4表达与癌旁腺瘤长径相关(P <0.05),LC3Ⅱ和p62表达与腺癌长径和癌旁腺瘤长径相关(P <0.05)。PDCD4在P-NIMM中主要表达于细胞核,而在腺癌中主要表达于细胞质。P-NIMM的PDCD4核/质表达比明显高于P-LGIN、P-HGIN和腺癌(P <0.05),P-LGIN、P-HGIN的核/质表达比明显高于腺癌(P <0.05)。腺癌中LC3Ⅱ和p62的阳性表达率明显高于P-NIMM和P-LGIN(P <0.05)。在P-LGIN、P-HGIN和腺癌中,PDCD4表达与LC3Ⅱ、p62表达均呈负相关(P <0.05)。生物信息学分析结果显示PDCD4表达在包括结直肠癌在内的多种恶性肿瘤中降低(P <0.05)。结论:细胞凋亡受抑和自噬激活可能促进了结直肠癌的发生,其机制可能为PDCD4的细胞内转位可抑制细胞凋亡,并增强自噬作用,而自噬激活后又可通过降解PDCD4进一步减弱其抑癌作用。Background: Endoscopic submucosal dissection( ESD) has become the preferred treatment of early colorectal cancer. PDCD4 and autophagy have important clinical significance in the pathogenesis of colorectal cancer. Aims: To explore the expressions and significance of apoptosis factor PDCD4 and autophagy factors LC3 Ⅱ and p62 in colorectal cancer. Methods: Fifty-four early colorectal adenocarcinoma patients treated by ESD from Jan. 2015 to Nov. 2020 at Binzhou Medical University Hospital were collected. The expressions of PDCD4,LC3 Ⅱ and p62 were detected by immunohistochemistry,and the correlations with clinicopathological factors were analyzed. The differential expression of PDCD4 in pan-cancer was analyzed by bioinformatics analysis. Results: Expression of PDCD4 was associated with the long-diameter of paracancer adenoma( P < 0. 05),and expressions of LC3 Ⅱ and p62 were associated with the longdiameters of adenocarcinoma and paracancer adenoma( P < 0. 05). The positive expression of PDCD4 in P-NIMM was located in the nucleus,while the positive expression in adenocarcinoma was located in cytoplasm. The nucleus/cytoplasm ratio of PDCD4 was significantly higher in P-NIMM than in P-LGIN,P-HGIN and adenocarcinoma( P < 0. 05),and the nucleus/cytoplasm ratio of PDCD4 was significantly higher in P-LGIN,P-HGIN than in adenocarcinoma( P < 0. 05). The positive expression rates of LC3Ⅱ and p62 were significantly higher in adenocarcinoma than in P-NIMM and P-LGIN( P <0. 05). In P-LGIN,P-HGIN and adenocarcinoma,the expression of PDCD4 was negatively correlated with the expressions of LC3Ⅱ and p62( P < 0. 05). The bioinformatics analysis showed that expression of PDCD4 was significantly reduced in a variety of malignant tumors including colorectal cancer( P < 0. 05). Conclusions: The inhibition of apoptosis and activation of autophagy may promote the occurrence of colorectal cancer,and its mechanism may be related to the intracellular transposition of PDCD4 that inhibits cell apoptosis and enhances autophagy,and activ

关 键 词：结直肠肿瘤 程序性细胞死亡因子4 自噬 腺瘤 

分 类 号：R735.34[医药卫生—肿瘤]