南方医科大学学报

南方医科大学学报 ›› 2022, Vol. 42 ›› Issue (5): 633-640.doi: 10.12122/j.issn.1673-4254.2022.05.02

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ALDH3B1的表达与肿瘤组织病理学和远期预后相关

李晴晴，邱权威，张乐乐，张小凤，王月月，耿志军，葛思堂，左芦根，宋 雪，李 静，胡建国   

  1. 蚌埠医学院第一附属医院检验科，胃肠外科，中心实验室，安徽 蚌埠 233000；蚌埠医学院，安徽 蚌埠 233030；蚌埠医学院组织移植重点实验室，安徽 蚌埠 233000
  • 出版日期:2022-05-20 发布日期:2022-06-02

ALDH3B1 expression is correlated with histopathology and long-term prognosis of gastric cancer

LI Qingqing, QIU Quanwei, ZHANG Lele, ZHANG Xiaofeng, WANG Yueyue, GENG Zhijun, GE Sitang, ZUO Lugen, SONG Xue, LI Jing, HU Jianguo   

  1. Clinical Laboratory, Department of Gastrointestinal surgery, Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China; Bengbu Medical College, Bengbu 233030, China; Key Laboratory of tissue transplantation, Bengbu Medical College, Bengbu 233000, China
  • Online:2022-05-20 Published:2022-06-02

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摘要： 目的 探究乙醛脱氢酶3B1（ALDH3B1）在胃癌组织中的表达情况，明确其与胃癌病理参数和远期预后的关系。方法 纳入分析我院行胃癌根治术患者101例，治疗时间范围在2013年1月~2016年11月，采用免疫组织化学法检测胃癌和癌旁组织中ALDH3B1的表达，统计学分析ALDH3B1与病理组织学参数的关系以及对胃癌术后远期生存的预测评估价值；对MGC-803胃癌细胞系采用慢病毒特异性干扰和过表达ALDH3B1，经免疫印迹法验证基因调控效果，实验分为正常对照组（NC），干扰组（Si-ALDH3B1）和过表达组（LV-ALDH3B1），探究ALDH3B1作用于胃癌细胞恶性行为的影响。结果 胃癌组织中ALDH3B1 和Ki67的表达显著增加（P<0.05）；胃癌组织中ALDH3B1表达量与外周血CEA及CA19-9间均存在正相关关系（P<0.01）。ALDH3B1高表达组患者CEA≥5 μg/L、CA19-9≥37 kU/L、T分期为3~4期及N分期为2~3期的比例显著高于ALDH3B1低表达组（P<0.05）。K-M生存分析结果显示ALDH3B1高表达组患者5年生存率显著降低（P<0.01）。经单因素及Cox多元回归模型分析得出ALDH3B1高表达（P<0.05，HR=0.231，95% CI：0.064~0.826）、CEA≥5 μg/L（P<0.01，HR=4.478，95% CI：1.530~13.110）、CA19-9≥37 kU/L（P<0.01，HR=3.877，95% CI：1.625~9.247）、T 分期为 3~4 期（P<0.01，HR=4.953，95% CI：1.768~13.880）及N分期为2~3期（P<0.05，HR=2.152，95% CI：1.152~4.022）为影响胃癌根治术后5年生存期的独立危险因素。此外，以ALDH3B1相对表达量4.66为截点值，预判术后5年死亡的敏感性为76.47%，特异性为76%（P<0.01）；细胞学实验证明ALDH3B1高表达可促进胃癌细胞的增殖、迁移及侵袭能力。结论 ALDH3B1在胃癌组织中高表达与肿瘤病理学参数相关，是胃癌根治术后5年生存率的独立危险因素，可能促进肿瘤细胞的增殖、侵袭及转移等生物学过程。

关键词: 胃癌；乙醛脱氢酶3B1；病理；生存分析；危险因素分析

Abstract: Objective To investigate the expression of aldehyde dehydrogenase 3B1 (ALDH3B1) in gastric cancer and explore its correlation with the pathological parameters and long-term prognosis of the patients. Methods We analyzed the clinical data of 101 patients who underwent radical gastrectomy for gastric cancer in our hospital between January, 2013 and November, 2016, and examined the expression of ALDH3B1 in paraffin-embedded samples of gastric cancer tissues and adjacent tissues from these cases by immunohistochemical staining. We evaluated the correlation between ALDH3B1 expressions and histopathological parameters and assessed the predictive value of ALDH3B1 expression for long-term survival of the patients. We also examined the effect of lentivirus-mediated interference and overexpression of ALDH3B1 on the malignant behaviors of MGC- 803 gastric cancer cells. Results The expressions of ALDH3B1 and Ki67 were significantly higher in gastric cancer tissues than in adjacent tissues (P<0.05). In gastric cancer patients, ALDH3B1 expression was positively correlated with peripheral blood CEA and CA19-9 levels (P<0.01). The proportion of patients with CEA ≥5 μg/L, CA19-9 ≥37 kU/L, T stage of 3- 4, and N stage of 2-3 was significantly greater in high ALDH3B1 expression group than in low expression group. Kaplan-Meier survival analysis showed that the 5-year survival rate was significantly lower in gastric cancer patients with high ALDH3B1 expressions (P<0.01). Univariate and Cox multiple regression analyses identified a high expression of ALDH3B1 (P<0.05, HR=0.231, 95% CI: 0.064-0.826), CEA≥5 μg/L (P<0.01, HR=4.478, 95% CI: 1.530-13.110), CA19-9≥37 kU/L (P<0.01, HR=3.877, 95% CI: 1.625-9.247), T stage of 3-4 (P<0.01, HR=4.953, 95% CI: 1.768-13.880), and N stage of 2-3 (P<0.05, HR=2.152, 95% CI: 1.152-4.022) as independent risk factors affecting 5-year survival after radical gastrectomy. The relative ALDH3B1 expression level, at the cut-off point of 4.66, showed a sensitivity of 76.47% and a specificity of 76% for predicting 5-year postoperative death (P<0.01). In the cell experiment, overexpression of ALDH3B1 obviously promoted the proliferation, migration and invasion of MGC-803 cells. Conclusion As an independent risk factor affecting 5-year survival after radical gastrectomy, ALDH3B1 is highly expressed in gastric cancer and correlated with pathological parameters of the tumor, and a high ALDH3B1 expression may promote proliferation, invasion and metastasis of gastric cancer cells.

Key words: gastric cancer; aldehyde dehydrogenase 3B1; pathology; survival analysis; risk factor analysis