High expression of CREM is associated with poor prognosis in gastric cancer patients

doi:10.12122/j.issn.1673-4254.2024.09.18

Abstract

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

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.

Figures/Tables 6

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.

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

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.

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)

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.

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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