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410013 长沙,中南大学湘雅医学院附属肿瘤医院,湖南省肿瘤医院泌尿外科
[谢宇,E-mail:xieyu420@sina.com XIE Yu, E-mail: xieyu420@sina.com
收稿:2021-06-06,
修回:2021-09-19,
纸质出版:2021-12-15
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朱帅, 文育恒, 梁宇, 等. HMGCS2在膀胱癌中的表达及其与临床病理特征的相关性分析[J]. 第三军医大学学报, 2021,43(23):2552-2561.
Shuai ZHU, Yuheng WEN, Yu LIANG, et al. Expression of HMGCS2 and its correlation with clinopathological characteristics in bladder cancer[J]. Journal of Third Military Medical University, 2021, 43(23): 2552-2561.
朱帅, 文育恒, 梁宇, 等. HMGCS2在膀胱癌中的表达及其与临床病理特征的相关性分析[J]. 第三军医大学学报, 2021,43(23):2552-2561. DOI: 10.16016/j.1000-5404.202106042.
Shuai ZHU, Yuheng WEN, Yu LIANG, et al. Expression of HMGCS2 and its correlation with clinopathological characteristics in bladder cancer[J]. Journal of Third Military Medical University, 2021, 43(23): 2552-2561. DOI: 10.16016/j.1000-5404.202106042.
目的
2
探索3-羟甲基戊二酰辅酶A合酶2(3-hydroxy-3-methylglytaryl-CoA synthetase 2
HMGCS2)在膀胱癌中的表达水平及其与患者临床病理特征的相关性。
方法
2
利用GEO数据库筛选肌层浸润性膀胱癌与非肌层浸润性膀胱癌中有显著差异性表达的基因,GEPIA数据库对筛选的公共差异表达基因进行生存分析;Metascape数据库对HMGCS2及其相关基因进行功能富集分析;免疫组化染色检测临床手术切除膀胱癌样本中HMGCS2的蛋白表达情况,卡方检验分析其与患者临床病理特征的关系,Cox回归分析验证其预后效能。
结果
2
GEO数据库的转录组数据显示,与非肌层浸润性膀胱癌相比,HMGCS2在肌层浸润性膀胱癌中显著低表达(7.42±2.51
vs
9.38±2.78,
P
<
0.05);GEPIA数据库的生存分析显示,高表达HMGCS2的膀胱癌患者预后较好(总体生存期:风险比
HR
=0.6,
P
=0.028;疾病无进展生存期:
HR
=0.59,
P
=0.036);KEGG、GO功能富集分析表明,HMGCS2可能参与细胞的脂肪代谢、细胞凋亡及铂类耐药,并涉及mTOR通路的信号转导;卡方检验显示HMGCS2的表达与T分期(
P
<
0.001)、组织学分级(
P
=0.006)、患者存活状态(
P
<
0.001)及患者疾病无进展状态(
P
<
0.001)显著相关;单因素Cox回归分析显示,HMGCS2与患者的总体生存率及疾病无进展生存率显著相关(总体生存期:
HR
=0.104,
P
<
0.001;疾病无进展生存期:
HR
=0.155,
P
<
0.001);多因素Cox回归分析显示,HMGCS2是评估患者预后风险的独立预测因子(总体生存期:
HR
=0.181,
P
<
0.001;疾病无进展生存期:
HR
=0.312,
P
<
0.001)。
结论
2
HMGCS2在肌层浸润性膀胱癌中低表达,低表达的HMGCS2与患者的不良预后密切相关。
Objective
2
To explore the expression of 3-hydroxymethylglutaryl-CoA synthase 2 (HMGCS2) and its correlation with the clinicopathological characteristics of patients with bladder cancer.
Methods
2
The GEO database was used to screen genes that were significantly differentially expressed between muscle invasive bladder cancer and non-muscle invasive bladder cancer. The survival analysis of the screened public differentially expressed genes was performed by gene expression profiling interactive analysis (GEPIA). The Metascape database was used for the functional enrichment analysis of HMGCS2 and its related genes. The expression of HMGCS2 was detected with immunohistochemical staining in clinical samples from patients with bladder cancer.
Chi
-square test was used to analyze the relationship between the expression of HMGCS2 and the clinicopathological c
haracteristics
and Cox regression analysis was adopted to verify the prognostic efficacy of HMGCS2.
Results
2
The transcriptome data of the GEO database showed HMGCS2 had significantly lower expression in muscle invasive bladder cancer compared with non-muscle invasive bladder cancer (7.42±2.51
vs
9.38±2.78
P
<
0.05). The survival analysis of the GEPIA database showed that patients with high expression of HMGCS2 had better prognosis (overall survival:
HR
=0.6
P
=0.028; disease progression-free survival:
HR
=0.59
P
=0.036); KEGG pathway analysis and GO functional enrichment analysis showed that HMGCS2 might be involved in fat metabolism
cell apoptosis and platinum resistance
and exerted effect on the signal transduction of the mTOR pathway. In addition
the
Chi
-square test showed the expression of HMGCS2 was significantly related to the T stage (
P
<
0.001)
tissue grade (
P
=0.006)
patients' overall survival status (
P
<
0.001) and patients' disease-free survival status (
P
<
0.001); Univariate Cox regression analysis showed that HMGCS2 was related to the patients' overall survival rate and the disease progression-free survival rate (OS:
HR
=0.104
P
<
0.001; DFS:
HR
=0.155
P
<
0.001); multivariate Cox regression analysis indicated that HMGCS2 was an independent predictor of the prognostic risk of patients (OS:
HR
=0.181
P
<
0.001; DFS:
HR
=0.312
P
<
0.001).
Conclusion
2
HMGCS2 is lowly expressed in muscle invasive bladder cancer
and its low expression is closely related to the poor prognosis of patients.
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