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[摘要]
目的:探讨结直肠癌(CRC)组织中磷酸甘油酸变位酶1(PGAM1)的表达及其与患者预后的关系,研究PGAM1 对CRC细胞增殖、迁移和侵袭的影响。方法:选择2003 年3月至2008 年11月间在天津医科大学肿瘤医院手术切除的30例CRC患者的肿瘤组织标本及临床资料,采用免疫组织化学染色法检测CRC组织中PGAM1蛋白的表达,分析PGAM1表达与患者临床病理特征的关系,Kaplan-Meier 生存分析法比较PGAM1 高表达与低表达患者的OS、PFS 来评价PGAM1 表达与患者预后的关系。利用RNA干扰技术分别将si-PGAM1及si-NC 质粒转染至HCT-116和SW480 细胞,WB法检测转染细胞中PGAM1蛋白的表达水平,CCK-8、Transwell 实验分别检测敲低PGAM1对CRC细胞增殖、迁移和侵袭的影响。结果:30 例CRC组织中PGAM1阳性染色定位于CRC细胞的细胞质,其中33.3%(10/30 例)呈高表达。虽然PGAM1高表达与CRC患者年龄、性别、组织学类型、肿瘤大小、淋巴结转移、远处转移及临床TNM分期无关(均P>0.05),但是PGAM1 高表达与低表达患者相比其OS、PFS 显著缩短。在CRC 细胞中敲低PGAM1 后,细胞的增殖、迁移和侵袭能力均显著降低(均P<0.05)。结论:CRC 组织中PGAM1 呈高表达,PGAM1高表达的患者预后较差;敲低PGAM1后细胞的增殖、迁移及侵袭能力均显著降低,提示PGAM1可能是CRC患者预后的生物标志物。
[Key word]
[Abstract]
Objective::To investigate the expression of phosphoglycerate mutase 1 (PGAM1) in colorectal cancer (CRC) tissues and its correlation with the prognosis and explore its effects on the proliferation, migration and invasion of CRC cells. Methods: Cancer tissue samples and clinical data of 30 patients who underwent surgery at Tianjin Medical University Cancer Institute and Hospital between March 2003 and November 2008 were collected. Immunohistochemical staining was used to detect the protein expression of PGAM1 in CRC tissues and analyze the relationship between PGAM1 expression and patients’ clinicopathological characteristics. Kaplan‐Meier survival analysis was employed to compare the overall survival (OS) and progress-free survival (PFS) of patients with high and low PGAM1 expression in order to analyze the relationship between PGAM1 expression and the prognosis. HCT-116 and SW480 cells were transfected respectively with si-PGAM1 and si-NC plasmids using RNA interference technology. Western blotting was used to detect PGAM1 protein expression levels in cells transfected with si-PGAM1 and si-NC. Afterwards, CCK-8 and Transwell assays were used to detect the influence of PGAM1 knockdown on the proliferation, migration, and invasion of CRC cells. Results: In 30 CRC tissue samples, PGAM1 positive staining was localized in the cytoplasm of CRC cells, and 33.3% (10 among 30 samples) showed high PGAM1 expression levels. Although the high expression of PGAM1 had no correlation with sex, age, histological type, tumor size,lymph node metastasis, distant metastasis and TNM stage of CRC patients (all P>0.05), the OS and PFS was significantly shorter in patients with PGAM1 high expression than those with low expression. After PGAM1 knockdown the proliferation, migration and invasion abilities of CRC cells were greatly inhibited (all P<0.05). Conclusion: PGAM1 was highly-expressed in CRC tissues. The high expression of PGAM1 was correlated with poor prognosis. Knocking down PGAM1 significantly inhibited the proliferation,migration and invasion abilities of CRC cells. All these findings suggest that PGAM1 might be a promising biomarker for predicting the prognosis of CRC patients.
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[基金项目]
国家自然科学基金(No. 81974416);天津市医学重点学科(专科)建设项目(No. TJYXZDXK-009A)