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. 2022 May 20;42(5):633-640.
doi: 10.12122/j.issn.1673-4254.2022.05.02.

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

[Article in Chinese]
Q Li  1   2 , Q Qiu  2   3 , L Zhang  2   4 , X Zhang  5 , Y Wang  1 , Z Geng  5 , S Ge  3 , L Zuo  3 , X Song  5 , J Li  1 , J Hu  1
Affiliations

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

[Article in Chinese]
Q Li et al. Nan Fang Yi Ke Da Xue Xue Bao. .

Abstract
in English, Chinese

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.

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。

Keywords: aldehyde dehydrogenase 3B1; gastric cancer; pathology; risk factor analysis; survival analysis.

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Figures

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ALDH3B1和Ki67在胃癌组织及癌旁组织中的细胞定位及表达 Localization and expression of ALDH3B1 and Ki67 in gastric cancer and adjacent tissues. A: Immunohistochemical staining of ALDH3B1. B: Immunohistochemical staining of Ki67. C, D: ALDH3B1 relative IOD value and analysis of mRNA expression. E: Relative IOD of Ki67. *P < 0.05 vs paracancerous tissue.
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胃癌组织中ALDH3B1与外周血CEA及CA19-9间的相关性分析 Correlation of ALDH3B1 with CEA and CA19-9 levels in peripheral blood of gastric cancer patients.A: Correlation betweenALDH3B1 and CEA. B: Correlation betweenALDH3B1 and CA19-9.
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K-M生存曲线分析ALDH3B1表达与胃癌根治术后5年生存率的关系 Kaplan-Meier survival analysis of the correlation between ALDH3B1 expression and 5- year survival rate of gastric cancer patients after radical gastrectomy.
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ALDH3B1和Ki67表达量对胃癌根治术后5年生存情况的预判价值 Predictive value of ALDH3B1 (A) and Ki67 expression (B) for 5-year survival of gastric cancer patients after radical gastrectomy
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5
ALDH3B1促进胃癌细胞增殖 ALDH3B1 promotes the proliferation of gastric cancer cells. A: Western blotting of LV-ALDH3B1 expressions; B: Analysis of relative LV-ALDH3B1 intensity; C: Western blotting of Si-ALDH3B1 expressions; D: Analysis of relative Si-ALDH3B1 intensity; E: A450 nm of CCK-8. NC: Normal control; Si: siRNA; LV: overexpression. *P < 0.05 vs NC.
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ALDH3B1促进胃癌细胞迁移和侵袭 ALDH3B1 overexpression promotes migration and invasion of gastric cancer cells. A: Transwell. B: Cell number of migration. C: Cell number of invasion. NC: Normal control; Si: siRNA; LV: Overexpression. *P < 0.05 vs NC.
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