CREM在胃癌中高表达并与患者的不良预后相关

doi:10.12122/j.issn.1673-4254.2024.09.18

摘要/Abstract

摘要：

目的分析CREM在胃癌中的表达及其与临床预后的相关性。方法利用TCGA和GEO数据库分析胃癌和癌旁组织CREM mRNA表达差异，免疫组化染色（IHC）分析43例胃癌和配对癌旁组织的CREM蛋白表达差异，分析CREM表达与胃癌患者临床病理特征之间的关系；采用Kaplan-Meier生存分析探讨CREM表达水平与胃癌患者生存期之间的关系；利用LinkedOmics数据库注释CREM相关基因的GO功能和KEGG通路的富集情况。结果数据库分析显示，CREM在胃癌组织中高表达（P<0.05），与胃癌患者的不良预后正相关（P=0.01）。IHC结果显示，与癌旁组织相比，胃癌组织中CREM高表达（P<0.0001），CREM表达水平与T分期和N分期有关（P<0.05），CREM高表达的胃癌患者总生存期更短（RR=4.02，P=0.0046）。基因富集分析显示，CREM可能通过细胞黏附分子介导的信号通路促进胃癌发生发展。结论 CREM在胃癌中高表达提示不良预后，CREM可作为候选的胃癌预后指标。

关键词: 胃癌, CREM, 免疫组化, 生物信息学, 预后

Abstract:

Objective To analyze the expression of CREM in gastric cancer (GC) and its correlation with prognosis of the patients. Methods TCGA and GEO databases were used to analyze the expression levels of CREM mRNA in GC and adjacent tissues. Immunohistochemistry was used to examine the expression of CREM protein in 43 pairs of GC and adjacent tissues, and the correlation of CREM expression with clinicopathological features of the patients was analyzed. Kaplan-Meier survival analysis was used to explore the relationship between CREM expression and survival of GC patients. LinkedOmics database was used to annotate the GO function and KEGG pathway enrichment of CREM-related genes. Results Database analysis showed that CREM was highly expressed in GC tissues (P<0.05) and positively correlated with poor prognosis in GC patients (P=0.01). Immunohistochemistry results showed significantly higher CREM expression in GC tissues than in paired adjacent tissues (P<0.0001), and its expression level was correlated with T-stage and N-stage of the tumor (P<0.05). The overall survival of GC patients with high expression of CREM was shorter (RR=4.02, P=0.0046). Gene enrichment analysis showed that high CREM expression promotes occurrence and progression of GC very likely through the cell adhesion signaling pathway. Conclusion CREM is highly expressed in GC, and its high expression is associated with a poor prognosis of GC patients, suggesting the potential of CREM to serve as a prognostic indicator for GC.

Key words: gastric cancer, CREM, bioinformatics, immunohistochemistry, prognosis

叶梦楠, 武鸿美, 梅琰, 张庆玲. CREM在胃癌中高表达并与患者的不良预后相关[J]. 南方医科大学学报, 2024, 44(9): 1776-1782.

Mengnan YE, Hongmei WU, Yan MEI, Qingling ZHANG. High expression of CREM is associated with poor prognosis in gastric cancer patients[J]. Journal of Southern Medical University, 2024, 44(9): 1776-1782.

图/表 6

图1 CREM在多种恶性肿瘤中的差异性表达

Fig.1 Differential expression of CREM in different cancers based on data from TCGA-GTEx (A) and TCGA (B) databases. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

图2 CREM与胃癌Estimate免疫浸润评分的相关性

Fig.2 Correlation between CREM expression level and Estimate immune infiltration scores in gastric cancer.

图3 CREM在胃癌组织中高表达

Fig.3 CREM is highly expressed in gastric cancer tissues. A: Expression of CREM in gastric cancer and adjacent tissues in TCGA database. B: Differential expression of CREM in tumors in different T-stages. C-E: Differential expression of CREM in gastric cancer tissues and adjacent tissues in GSE65801, GSE63089, and GSE54129 datasets. F, G: Immunohistochemical staining of CREM in gastric cancer and adjacent tissues and the immunohistochemical scores. *P<0.05, ****P<0.0001.

表1 43例胃癌患者CREM的表达与临床病理特征的关系

Tab. 1 Relationship between CREM expression and clinicopathological features of 43 patients with STAD

Characteristic	n	CREM Expression		χ²	P
Characteristic	n	Low (n=11)	High (n=32)	χ²	P
Age (year)				1.815	0.178
<60	15	2 (13.3)	13 (86.7)
≥60	28	9 (32.1)	19 (67.9)
Gender				1.120	0.290
Male	29	6 (20.7)	23 (79.3)
Female	14	5 (35.7)	9 (64.3)
Ki-67(%)				1.120	0.290
<50	14	5 (35.7)	9 (64.3)
≥50	29	6 (20.7)	23 (79.3)
Tumor size (cm)				2.516	0.113
<4	15	6 (40.0)	9 (60.0)
≥4	28	5 (17.9)	23 (82.1)
T stage				10.862	0.001
T₁-T₂	14	8 (57.1)	6 (42.9)
T₃-T₄	29	3 (10.3)	26 (89.7)
N stage				4.418	0.036
N₀	16	7 (43.8)	9 (56.2)
N₁-N₃	27	4 (14.8)	23 (85.2)
TNM staging				3.376	0.066
I-II	21	8 (38.1)	13 (61.9)
III-IV	22	3 (13.6)	19 (86.4)

图4 CREM高表达与胃癌患者预后不良相关

Fig.4 High CREM expression is associated with poor prognosis in gastric cancer patients. A-C: FP, OS, and PPS curves of gastric cancer patients with different CREM mRNA expression levels in the Kaplan-Meier Plotter database. D: OS curves of patients with high and low CREM protein expression in clinical gastric cancer samples.

图5 胃癌中CREM相关基因分析及KEGG、GO富集分析结果

Fig.5 Analysis of CREM-related genes and results of KEGG and GO enrichment analysis in gastric cancer. A, B: LinkedOmics database analysis of genes positively and negatively correlated with CREM expression in the TCGA gastric cancer dataset. C: GO enrichment analysis to explore the role of CREM in gastric cancer, including the biological process, cellular composition, and molecular function. D: KEGG enrichment analysis to explore the relevant molecular pathways of CREM in gastric cancer development.

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