摘要
目的分析结肠癌转移相关基因1(MACC1)在甲状腺乳头状癌(PTC)进展和转移中的作用。方法选取2018年3月至2020年12月在贵州医科大学附属医院行手术治疗的60例PTC患者(其中Ⅰ、Ⅱ、Ⅲ、Ⅳ期PTC分别为30例、12例、9例、9例)和30例甲状腺良性肿瘤患者的甲状腺组织标本,采用免疫组织化学方法检测甲状腺组织标本中MACC1的表达情况。使用慢病毒载体构建MACC1低表达的甲状腺乳头癌细胞株TPC-1,利用四唑盐比色法、划痕实验、Transwell等实验研究MACC1对TPC-1的增殖、迁移及侵袭能力的影响。结果年龄≥55岁、肿瘤直径≥2 cm、中央区淋巴结侵犯PTC组织MACC1阳性表达率分别高于年龄<55岁、肿瘤直径<2 cm、无中央区淋巴结侵犯PTC组织(P<0.05或P<0.01)。不同性别、肿瘤个数、是否合并桥本甲状腺炎、是否侧区淋巴结侵犯、不同临床分期PTC组织MACC1阳性表达率比较差异无统计学意义(P>0.05)。免疫组织化学染色分析结果显示,PTC组织标本中MACC1阳性表达率显著高于甲状腺良性肿瘤组织标本[80.3%(50/60)比10.0%(3/30)](P<0.01),且Ⅰ~Ⅱ期PTC组织标本中MACC1阳性表达率低于Ⅲ~Ⅳ期PTC组织标本[64.3%(27/42)比100.0%(18/18)](P<0.01)。细胞转染96 h后,三组细胞A 490 nm值和细胞克隆数目比较差异有统计学意义(P<0.01),KD组细胞A 490 nm值、细胞克隆数目明显低于NC组、空白对照组[0.317±0.012比0.580±0.010、0.623±0.035,(51.3±2.6)个比(114.2±2.0)个、(117.6±4.4)个](P<0.01),但空白对照组和NC组细胞A 490 nm值、细胞克隆数目比较差异无统计学意义(P>0.05)。流式细胞实验结果显示,三组细胞凋亡百分比比较差异有统计学意义(P<0.001),其中KD组细胞凋亡百分比明显高于空白对照组和NC组[(13.68±0.07)%比(1.25±0.04)%、(1.35±0.05)%](P<0.01);而空白对照组和NC组细胞凋亡百分比比较差异无统计学意义(P>0.05)。划痕实验结果显示,三组细胞划痕8 h和划痕24 h迁移率比较差异有统计学意义(P<0.05),KD组细胞划痕8 h、24 h的迁移率均明显低于NC组和空白对照组[(0.06±0.01)%比(0.12±0.03)%、(0.14±0.04)%,(0.09±0.01)%比(0.32±0.05)%、(0.36±0.09)%](P<0.05)。Transwell小室侵袭实验结果显示,三组细胞的侵袭数目比较差异有统计学意义(P<0.01),KD组细胞侵袭数目明显低于NC组、空白对照组[(44.0±2.0)个比(118.0±2.0)个、(119.0±1.0)个](P<0.01),NC组和空白对照组细胞侵袭数目比较差异无统计学意义(P>0.05)。结论MACC1在PTC组织中高表达,可能参与了PTC的侵袭转移。
Objective To investigate the role of metastasis-associated in colon cancer 1(MACC1)in the progression and metastasis of papillary thyroid carcinoma(PTC).Methods Thyroid tissue samples were selected from 60 patients with PTC undergoing surgical treatment in the Affiliated Hospital of Guizhou Medical University from Mar.2018 to Dec.2020(including 30 patients with stageⅠ,12 patients with stageⅡ,9 patients with stageⅢ,9 patients with stageⅣPTC)and 30 patients with benign thyroid tumors,respectively.The expression of MACC1 in thyroid tissue samples was detected by immunohistochemical method.Lentiviral vector was used to construct thyroid papillary cancer cell line TPC-1 with low expression of MACC1.The effects of MACC1 on the proliferation,migration and invasion of TPC-1 were studied by methyl thiazolyl tetrazolium assay,scratch assay and Transwell assay.Results The positive expression rate of MACC1 in PTC tissue of patients with age≥55 years,tumor diameter≥2 cm and central lymph node invasion was higher than that in PTC tissue of patients with age<55 years,tumor diameter<2 cm and no central lymph node invasion,respectively(P<0.05 or P<0.01).There was no significant difference in the MACC1 positive expression rate of PTC tissues by gender,number of tumors,whether complicated with Hashimoto thyroiditis,whether with lateral lymph node invasion,and different clinical stages(P>0.05).Immunohistochemical staining showed that the positive expression rate of MACC1 in PTC tissue specimens was significantly higher than that in benign thyroid tumor tissue specimens[80.3%(50/60)vs 10.0%(3/30)](P<0.01),andthe positive expression rate of MACC1 in PTC tissue specimens of stagesⅠandⅡwas lower than that of PTC tissue specimens of stagesⅢandⅣ[64.3%(27/42)vs 100.0%(18/18)](P<0.01).After transfection for 96 h,the A 490 nm value and number of cell clones in the three groups were statistically significantly different(P<0.01),that the A 490 nm value and number of cell clones in KD group were significantly lower than those in NC group and blank control group[0.317±0.012 vs 0.580±0.010,0.623±0.035,(51.3±2.6)vs(114.2±2.0),(117.6±4.4)](P<0.01),while there was no significant difference in A 490 nm value and number of cell clones between the blank control group and NC group(P>0.05).Flow cytometry showed that the percentage of apoptosis in the three groups was significantly different(P<0.01),and the percentage of apoptosis in the KD group was significantly higher than that in the blank control group and the NC group[(13.68±0.07)%vs(1.25±0.04)%,(1.35±0.05)%](P<0.01),while there was no significant difference in the percentage of apoptosis between the blank control group and the NC group(P>0.05).The results of scratch test showed that there was statistically significant difference in the mobility of cells at 8 h and 24 h of scratch among the three groups(P<0.05),that the mobility at 8 h and 24 h of scratch in the KD group were significantly lower than those in the NC group and the blank control group[(0.06±0.01)%vs(0.12±0.03)%,(0.14±0.04)%;(0.09±0.01)%vs(0.32±0.05)%,(0.36±0.09)%](P<0.05).The results of Transwell cell invasion showed that there was significant difference in the number of cells invaded among the three groups(P<0.01),that the number of invasive cells in the KD group was significantly lower than those in the NC group and the blank control group[(44.0±2.0)vs(118.0±2.0),(119.0±1.0)](P<0.01),while there was no significant difference between the NC group and the blank control group(P>0.05).Conclusion MACC1 is highly expressed in PTC tissues,which may be involved in the invasion and metastasis of PTC.
作者
张琛
王南鹏
张建勇
徐澍
ZHANG Chen;WANG Nanpeng;ZHANG Jianyong;XU Shu(Department of Thyroid Surgery,the Affiliated Hospital of Guizhou Medical University,Guiyang 550001,China;Guizhou Medical University,Guiyang 550001,China)
出处
《医学综述》
CAS
2023年第20期4308-4313,共6页
Medical Recapitulate
基金
贵州省科技合作计划项目(黔科合LH字〔2015〕7419号)。
关键词
甲状腺乳头状癌
结肠癌转移相关基因1
增殖
迁移
侵袭
Papillary thyroid carcinoma
Metastasis-associated in colon cancer 1
Proliferation
Migration
Invasion
