GPSM2 is highly expressed in gastric cancer to affect patient prognosis by promoting tumor cell proliferation

doi:10.12122/j.issn.1673-4254.2025.02.03

Abstract

Abstract:

Objective To explore the association between GPSM2 expression level and gastric cancer progression and analyze the functional pathways and action mechanism of GPSM2. Methods We analyzed GPSM2 expression levels in gastric cancer tumors based on data from the GEPIA database and the clinical data of 109 patients. Public databases enrichment analysis were used to assess the impact of GPSM2 expression level on survival outcomes and the functional pathways and action mechanism of GPSM2. We further observed the effects of GPSM2 knockdown and overexpression on proliferation, migration and apoptosis of MGC803 cells using CCK-8 assay, colony formation assay, flow cytometry and immunoblotting and on the growth of MGC803 cell xenografts in nude mice. Results Bioinformatic analysis and immunohistochemical staining of the clinical specimens both revealed high GPSM2 expressions in gastric cancer (P<0.01). A high GPSM2 expression was significantly correlated with T3-4 stages, N2-3 stages, a carcinoembryonic antigen (CEA) level ≥5 μg/L, and a carbohydrate antigen (CA) 19-9 level ≥37 kU/L (P<0.05). Cox regression analysis identified high GPSM2 expression as an independent risk factor affecting 5-year survival of the patients (P<0.05). Gene ontology (GO) analysis suggested that GPSM2 was involved in cell cycle regulation. In MGC803 cells, GPSM2 overexpression significantly promoted cell proliferation and G1/S transition and xenograft growth in nude mice. KEGG pathway enrichment analysis indicated that GPSM2 executed its biological functions by regulating the p53 signaling pathway, which was confirmed by the results of immunoblotting experiments showing suppression of p53 signaling pathway activity in GPSM2-over expressing MGC803 cells. Conclusion GPSM2 is highly expressed in gastric cancer to affect patient prognosis by promoting tumor cell proliferation and G1/S transition possibly via inhibiting the p53 pathway.

Key words: gastric cancer, GPSM2, prognosis, cell cycle, p53

Xue SONG, Yue CHEN, Min ZHANG, Nuo ZHANG, Lugen ZUO, Jing LI, Zhijun GENG, Xiaofeng ZHANG, Yueyue WANG, Lian WANG, Jianguo HU. GPSM2 is highly expressed in gastric cancer to affect patient prognosis by promoting tumor cell proliferation[J]. Journal of Southern Medical University, 2025, 45(2): 229-238.

Figures/Tables 9

Fig.1 GEPIA is highly expressed in gastric cancer tissues. A: Expression of GPSM2 in pan-cancer. B: Expression of GPSM2 in gastric cancer. C: Immunohistochemical staining of GPSM2. D: Relative integrated optical density (IOD) value of GPSM2. *P<0.05 vs adjacent tissue.

Fig.2 Association of GPSM2 expression level with clinicopathological parameters of gastric cancer patients. A, B: Expression levels of GPSM2 gene in tumor specimens with different cancer stages and lymph node metastasis status in the UALCAN database. **P<0.01 vs normal.

Tab.1 Relationship between GPSM2 expression in gastric cancer tissues and clinicopathological parameters of the patients

Clinicopathological parameters	Number of cases	GPSM2		χ ²	P
Clinicopathological parameters	Number of cases	Low expression (n=54)	High expression (n=55)	χ ²	P
Gender				0.002	0.962
Female	87	43	44
Male	22	11	11
Age (year)				2.080	0.149
<60	45	26	19
≥60	64	28	36
Tumor size (cm)				0.446	0.504
<5	41	22	19
≥5	68	32	36
Histological Grading				12.759	<0.001
G₁-G₂	60	39	21
G₃-G₄	49	15	34
T Stage				11.370	<0.001
T₁-T₂	59	38	21
T₃-T₄	50	16	34
N Stage				4.975	0.026
N₀-N₁	61	36	25
N₂-N₃	48	18	30
CEA (μg/L)				14.026	<0.001
<5	49	34	15
≥5	60	20	40
CA19-9 (kU/L)				12.556	<0.001
<37	52	35	17
≥37	57	19	38

Fig.3 High GPSM2 expression levels are associated with a decreased postoperative 5-year survival rate in gastric cancer patients. A-D: Analysis of the association of GPSM2 expression levels with over survival (OS), overall survival at 60 months (OS-5), first progression (FP) and post-progression survival (PPS) using Kaplan-Meier Plotter. E: Kaplan-Meier survival analysis demonstrating the impact of GPSM2 expression on 5-year survival rate of gastric cancer patients after gastrectomy. F: ROC curve analysis for evaluating the predictive value of GPSM2 expression for 5-year survival rates in gastric cancer patients following gastrectomy.

Tab.2 Univariate and multivariate Cox regression analysis of factors influencing 5-year survival rate of gastric cancer patients

Clinicopathological parameters	Univariate analysis		Multivariate analysis
Clinicopathological parameters	Log-rank χ²	P	HR	95% CI	P
Gender (female vs male)	0.157	0.692
Age (≥60 year vs <60 year)	1.188	0.276
Tumor size (≥5 cm vs <5 cm)	0.004	0.949
GPSM2 expression (high vs low)	32.418	<0.001	3.365	1.689-6.705	<0.001
G Stage (G₃-G₄vs G₁-G₂)	15.761	<0.001	1.421	0.769-2.626	0.262
T Stage (T₃-T₄vs T₁-T₂)	26.397	<0.001	3.406	1.762-6.584	<0.001
N Stage (N₂-N₃vs N₀-N₁)	21.542	<0.001	2.130	1.115-4.068	0.022
CEA (≥5 μg/L vs <5 μg/L )	37.810	<0.001	2.717	1.175-6.283	0.019
CA19-9 (≥37 kU/L vs <37 kU/L)	37.429	<0.001	3.592	1.577-8.183	0.002

Fig.4 Effect of GPSM2 knockdown (KD) and overexpression (OE) on cell cycle of gastric cancer cells. A: GO enrichment analysis. B, C: GPSM2 protein expression in MGC803 cells analyzed by Western blotting. D: Results of CCK-8 assay. E, F: Colony-forming assay. G, H: Effect of GPSM2 on cell cycle of MGC803 cells detected by flow cytometry. I, J: Expression of CDK2 and CDK4 analyzed by Western blotting. n=3, *P<0.05 vs NC group.

Fig.5 GPSM2 overexpression promotes subcutaneous graft tumor growth in nude mice. A: Gross observation of the dissected tumors in each group. B: Quantitative assessment of tumor volume in different groups (n=5). C, D: Expression of CDK2 and CDK4 in the xenografts. E, F: Expression of CDK2 and CDK4 in tumor tissues detected by immunohistochemical staining. n=5, *P<0.05 vs NC group.

Fig.6 GPSM2 overexpression suppresses expression of the p53 signaling pathway. A: KEGG enrichment analysis. B, C: Analysis of p53 and p21 expression in different groups of MGC803 cells. D, E: Analysis of p53 and p21 expression in the transplanted tumors from nude mice. n=3, *P<0.05 vs NC group.

Fig.7 GPSM2 overexpression promotes proliferation of gastric cancer cells possibly by suppressing expressions of proteins in the p53 signaling pathway. A, B: Measurement of p53 and p21 expression levels in the transplanted tumors. C, D: Expression of p53 and p21 in MGC803 cells. E, F: Colony-forming assay. n=3, *P<0.05 vs OE group.

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