乙醛脱氢酶家族18成员A1对结直肠癌预后的判断意义及其对骨髓细胞瘤原癌基因表达的影响

郭玉峰; 段江洁; 李琳; 卞修武; 余时沧

doi:10.16016/j.1000-5404.201806128

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乙醛脱氢酶家族18成员A1对结直肠癌预后的判断意义及其对骨髓细胞瘤原癌基因表达的影响

基础医学 | 更新时间：2026-01-09

- 乙醛脱氢酶家族18成员A1对结直肠癌预后的判断意义及其对骨髓细胞瘤原癌基因表达的影响
- Prognostic significance of P5CS in colorectal cancer and its effects on myelocytomatosis oncogene expression
- 第三军医大学学报 2018年40卷第21期页码：1911-1921
- 作者机构：
- 作者简介：
- 基金信息：
  
  国家重点研发计划(2016YFA0202104)
- DOI：10.16016/j.1000-5404.201806128
  中图分类号：
- 收稿：2018-06-20，
  
  纸质出版：2018-11-15
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郭玉峰, 段江洁, 李琳, 等. 乙醛脱氢酶家族18成员A1对结直肠癌预后的判断意义及其对骨髓细胞瘤原癌基因表达的影响[J]. 第三军医大学学报, 2018,40(21):1911-1921.

Yufeng GUO, Jiangjie DUAN, Lin Li, et al. Prognostic significance of P5CS in colorectal cancer and its effects on myelocytomatosis oncogene expression[J]. Journal of Third Military Medical University, 2018, 40(21): 1911-1921.
郭玉峰, 段江洁, 李琳, 等. 乙醛脱氢酶家族18成员A1对结直肠癌预后的判断意义及其对骨髓细胞瘤原癌基因表达的影响[J]. 第三军医大学学报, 2018,40(21):1911-1921. DOI： 10.16016/j.1000-5404.201806128.

Yufeng GUO, Jiangjie DUAN, Lin Li, et al. Prognostic significance of P5CS in colorectal cancer and its effects on myelocytomatosis oncogene expression[J]. Journal of Third Military Medical University, 2018, 40(21): 1911-1921. DOI： 10.16016/j.1000-5404.201806128.

摘要

Abstract

Objective

To explore the expression pattern of aldehyde dehydrogenase family 18 member A1 (ALDH18A1

also called pyrroline-5-carboxylate synthetase

P5CS) in colorectal cancer and its prognostic value for the patients

and to investigate the correlation between P5CS and myelocytomatosis oncogene (MYC)

as well as the effects which P5CS exerts on MYC expression.

Methods

Affymetrix mRNA analysis based on the cancer genome atlas (TCGA) and gene expression omnibus (GEO) datasets was performed to compare the expression of P5CS between colorectal cancer and normal human colon tissues. The correlation of P5CS protein level with the clinico-pathological characteristics of colorectal cancer was analyzed using contingency table analysis. Kaplan-Meier estimates and multivariate Cox regression analysis of overall survival were performed to evaluate the prognostic value of P5CS expression in the patients with colorectal cancer. Methyl-thiazolyldiphenyl-sulfophenyl-tetrazolium bromide (MTS) assay was used to detect the proliferation of colorectal cancer cell lines HT29 and HCT116 after P5CS knockdown. The correlation between P5CS expression and MYC expression was evaluated

and the effect of P5CS knockdown on the expression of MYC was measured by qRT-PCR and Western blotting. The correlation between P5CS and enrichment of MYC downstream target genes was defined by applying gene set enrichment analysis (GSEA).

Results

The expression of P5CS was significantly higher in colorectal cancer tissues

and was closely related to clinicopathological indexes of colorectal cancer

and exhibited significant prognostic value (

=1.996

95%

=1.012~3.939

=0.046). A significant positive correlation was observed between P5CS and MYC expression. Down-regulation of P5CS resulted in reduced cell proliferation of colorectal cancer cells

and inhibited MYC expression. The patients with high P5CS expression were significantly associated with enrichment of c-MYC target genes.

Conclusion

P5CS might serve as a biomarker with prognostic significance for colorectal cancer

and suppress the proliferation of colorectal cancer cells by regulating MYC expression.

关键词

Keywords

references

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