Expression of GNG4 protein and its prognostic significance in gastrointestinal stromal tumors

doi:10.3877/cma.j.issn.2095-2015.2025.01.002

Abstract

Abstract:

Objective

To investigate the expression of guanine nucleotide-binding protein gamma 4 (GNG4) and its clinicopathological and prognostic significance in gastrointestinal stromal tumors(GIST).

Methods

A total of 112 surgically resected GIST samples in Nantong First People's Hospital from January 2016 to December 2019 were systematically collected, and the expression of GNG4 in these tissue samples were detected by immunohistochemistry. The correlations between the expression of GNG4 and clinicopathological parameters were analyzed, and the prognostic value of GNG4 for GIST patients was evaluated by Kaplan-Meier curve as well as the univariate and multivariate Cox regression analysis.

Results

The positive signals of GNG4 protein expression were mainly located in the cytoplasm of GIST cells, and the positive rate of its expression was 59.8% (67/112). Compared with the negative expression group, patients with positive expression of GNG4 had higher mitotic index (χ²=5.630, P=0.018) and the proportion of moderate and high risk group (P=0.022). Kaplan-Meier curves showed that the 3-year disease free survival (DFS) rates were 51.8% and 82.9% for patients with positive and negative expression of GNG4, respectively, with a statistically significant difference (P=0.020). Subgroup analysis revealed that the positive expression of GNG4 was significantly correlated with worse prognosis of GIST patients at moderate and high risk, and the 3-year DFS rates were 31.1% and 73.8%, respectively (P=0.009).Univariate and multivariate Cox analysis suggested that AFIP risk stratification (HR=2.177, 95% CI:1.036-4.578, P=0.040) and the expression of GNG4 (HR=2.551, 95% CI: 1.081-6.021, P=0.033) were independent prognostic factors for GIST patients.

Conclusion

The positive expression of GNG4 may reflect the malignant potential of GIST, and it can be used as an independent prognostic biomarker to further identify high-risk populations.

Key words: Gastrointestinal stromal tumors, Guanine nucleotide-binding protein gamma 4(GNG4), Immunohistochemistry, Prognosis, Marker

Yue Wang, Heng Lu, Jie Cao, Bowen Lu. Expression of GNG4 protein and its prognostic significance in gastrointestinal stromal tumors[J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2025, 15(01): 6-10.

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Figures/Tables 5

References 25

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参数	例数	GNG4表达		χ ²/t值	P值
参数	例数	阴性(n=45)	阳性(n=67)	χ ²/t值	P值
年龄				0.014	0.907
＜65岁	58(51.8)	23(51.1)	35(52.2)
≥65岁	54(48.2)	22(48.9)	32(47.8)
性别				0.973	0.324
女	46(41.1)	21(46.7)	25(37.3)
男	66(58.9)	24(53.3)	42(62.7)
组织学类型				0.199	0.656
梭形细胞型	95(84.8)	36(86.7)	56(83.6)
上皮样细胞型	17(15.2)	9(13.3)	11(16.4)
肿瘤位置				0.005	0.945
胃	85(75.9)	34(75.6)	51(76.1)
小肠	27(24.1)	11(24.4)	16(23.9)
肿瘤大小				3.321	0.190
＜5cm	63(56.3)	30(66.7)	33(49.3)
5～10cm	33(29.5)	10(22.2)	23(34.3)
＞10cm	16(14.3)	5(11.1)	11(16.4)
有丝分裂指数				5.630	0.018
＜5/HPF	78(69.6)	37(82.2)	41(61.2)
≥5/HPF	34(30.4)	8(17.8)	26(38.8)
AFIP风险分层				7.632	0.022
极低/低危	70(62.5)	35(77.8)	35(52.2)
中危	15(13.4)	3(6.7)	12(17.9)
高危	27(24.1)	7(15.6)	20(29.9)

参数	例数	GNG4表达		χ ²/t值	P值
参数	例数	阴性(n=45)	阳性(n=67)	χ ²/t值	P值
年龄				0.014	0.907
＜65岁	58(51.8)	23(51.1)	35(52.2)
≥65岁	54(48.2)	22(48.9)	32(47.8)
性别				0.973	0.324
女	46(41.1)	21(46.7)	25(37.3)
男	66(58.9)	24(53.3)	42(62.7)
组织学类型				0.199	0.656
梭形细胞型	95(84.8)	36(86.7)	56(83.6)
上皮样细胞型	17(15.2)	9(13.3)	11(16.4)
肿瘤位置				0.005	0.945
胃	85(75.9)	34(75.6)	51(76.1)
小肠	27(24.1)	11(24.4)	16(23.9)
肿瘤大小				3.321	0.190
＜5cm	63(56.3)	30(66.7)	33(49.3)
5～10cm	33(29.5)	10(22.2)	23(34.3)
＞10cm	16(14.3)	5(11.1)	11(16.4)
有丝分裂指数				5.630	0.018
＜5/HPF	78(69.6)	37(82.2)	41(61.2)
≥5/HPF	34(30.4)	8(17.8)	26(38.8)
AFIP风险分层				7.632	0.022
极低/低危	70(62.5)	35(77.8)	35(52.2)
中危	15(13.4)	3(6.7)	12(17.9)
高危	27(24.1)	7(15.6)	20(29.9)

因素	Β值	SE	Wald	HR	95%CI	P值
年龄
≥65岁vs＜65岁	0.496	0.365	1.849	1.643	0.803～3.360	0.174
性别
男vs女	0.167	0.376	0.196	1.181	0.565～2.468	0.658
组织学类型
梭形细胞vs上皮样细胞型	-0.609	0.608	1.001	0.544	0.165～1.792	0.317
肿瘤位置
小肠vs胃	0.245	0.360	0.464	1.278	0.631～2.586	0.496
肿瘤大小
≥5cm vs ＜5cm	0.755	0.356	4.480	2.127	1.057～4.277	0.034
有丝分裂指数
≥5/HPF vs ＜5/HPF	0.781	0.380	4.229	2.184	1.037～4.598	0.040
AFIP 风险分层
中、高危vs极低/低危	1.035	0.367	7.925	2.814	1.369～5.783	0.005
GNG4 表达
阳性vs阴性	1.050	0.429	5.988	2.859	1.233～6.630	0.014

因素	Β值	SE	Wald	HR	95%CI	P值
年龄
≥65岁vs＜65岁	0.496	0.365	1.849	1.643	0.803～3.360	0.174
性别
男vs女	0.167	0.376	0.196	1.181	0.565～2.468	0.658
组织学类型
梭形细胞vs上皮样细胞型	-0.609	0.608	1.001	0.544	0.165～1.792	0.317
肿瘤位置
小肠vs胃	0.245	0.360	0.464	1.278	0.631～2.586	0.496
肿瘤大小
≥5cm vs ＜5cm	0.755	0.356	4.480	2.127	1.057～4.277	0.034
有丝分裂指数
≥5/HPF vs ＜5/HPF	0.781	0.380	4.229	2.184	1.037～4.598	0.040
AFIP 风险分层
中、高危vs极低/低危	1.035	0.367	7.925	2.814	1.369～5.783	0.005
GNG4 表达
阳性vs阴性	1.050	0.429	5.988	2.859	1.233～6.630	0.014

因素	Β值	SE	Wald	HR	95%CI	P值
肿瘤大小
≥5cm vs ＜5cm	0.136	0.559	0.059	1.145	0.383～3.428	0.808
有丝分裂指数
≥5/HPF vs ＜5/HPF	0.815	0.529	2.372	2.259	0.801～6.369	0.123
AFIP 风险分层
中、高危vs极低/低危	0.778	0.379	4.212	2.177	1.036～4.578	0.040
GNG4表达
阳性vs阴性	0.936	0.438	4.568	2.551	1.081～6.021	0.033

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