胃癌外周血TWA1 mRNA的表达与预后价值

doi:10.3877/cma.j.issn.1674-0793.2020.06.005

目的

检测胃癌（GC）患者外周血TWA1 mRNA表达水平，分析其与患者长期预后的关系。

方法

选择2016年6月至2017年6月于西宁市第二人民医院诊治的97例GC患者，实时荧光定量PCR（RT-PCR）检测外周血TWA1表达量，随访并记录患者无进展生存期（PFS）。受试者工作特征（ROC）曲线判定TWA1 mRNA的阈值，分组比较TWA1 mRNA不同表达患者的PFS情况。Cox回归模型评估TWA1 mRNA水平对GC患者预后的预测价值。

结果

随访（20.91±5.76）个月，随访率为94.79%（91/94），平均PFS（21.83±5.13）个月。TWA1 mRNA对GC患者PFS判定的曲线下面积为0.781（95% CI：0.687~0.875，P<0.001），截断值为1.27。TWA1 mRNA高表达患者的PFS显著短于低表达患者（χ²=14.415，P<0.01）。淋巴结转移（HR=3.328，95% CI：2.098~5.971，P=0.044）、TNM Ⅲ~Ⅳ期（HR=3.400，95% CI：1.114~4.795，P=0.011）及外周血TWA1 mRNA高表达（HR=7.429，95% CI：1.711~32.263，P=0.007）是影响患者PFS的独立危险因素。

结论

外周血TWA1的表达与GC患者PFS显著相关，TWA1 mRNA水平对GC患者随访预后情况具有较好的预测价值。

关键词: 胃肿瘤, TWA1, E3泛素连接酶复合物, 预后, 预测价值

Objective

To investigate the predictive value of peripheral blood TWA1 mRNA expression on the prognosis of patients with gastric cancer (GC).

Methods

A total of 97 GC patients treated in the Second People’s Hospital of Xining City from June 2016 to June 2017 were selected, and the TWA1 expression in peripheral blood was detected by real-time fluorescent quantitative PCR (RT-PCR). Patients were followed up and recorded for progression-free survival (PFS). The ROC curve was used to determine the threshold of peripheral blood TWA1 mRNA for PFS in GC patients. PFS of patients with different expression of TWA1 mRNA was compared. Finally, Cox regression analysis was used to analyze the influencing factors of patients’ PFS.

Results

The average follow-up time of all patients was (20.91±5.76) months, the follow-uprate was 94.79% with an average PFS of (21.83±5.13) months. The AUC for PFS of GC patients by TWA1 mRNA was 0.781 (95% CI: 0.687-0.875, P<0.001), and the Cut-off value was 1.27. PFS in patients with high TWA1 mRNA expression was significantly shorter (χ2=14.415, P<0.01). Lymph node metastasis (HR=3.328, 95% CI: 2.098-5.971, P=0.044), TNM Ⅲ-Ⅳ (HR=3.400, 95% CI: 1.114-4.795, P=0.011), and high expression of TWA1 mRNA in peripheral blood (HR=7.429, 95% CI: 1.711-32.263, P=0.007) were independent risk factors for PFS.

Conclusion

The expression of TWA1 in peripheral blood has a significant effect on the prognosis of GC patients, which has good predictive value for the prognosis ofGC patients.

Key words: Stomach neoplasms, TWA1, E3 ubiquitin ligase complex, Prognosis, Predictive value

图1 外周血TWA1对胃癌患者预后的预测性分析

图2 TWA1表达对胃癌患者无进展生存期（PFS）的影响

表1 97例胃癌患者基本临床资料

组别	例数	性别(例)		年龄(岁，±s)	瘤体最大直径(cm，±s)	血管浸润(例)	神经浸润(例)
组别	例数	男	女	年龄(岁，±s)	瘤体最大直径(cm，±s)	血管浸润(例)	神经浸润(例)
PFS组	63	40	25	58.07±7.24	2.56±0.75	21	30
非PFS组	28	16	10	58.31±6.14	2.96±0.85	15	13
统计值		χ²=0.129		t=0.154	t=2.645	χ²=7.569	χ²=0.078
P值		0.719		0.878	0.011	0.005	0.778
组别	淋巴结转移(例)	TWA1 mRNA(±s)	肿瘤位置(例)		TNM分期(例)		术后辅助化疗(例)
组别	淋巴结转移(例)	TWA1 mRNA(±s)	贲门	胃体胃窦	Ⅰ~Ⅱ	Ⅲ~Ⅳ	术后辅助化疗(例)
PFS组	33	1.07±0.26	30	33	43	20	46
非PFS组	24	1.37±0.27	15	13	7	21	17
统计值	χ²=9.203	t=5.003	χ²=0.274		χ²=14.651		χ²=1.377
P值	0.002	<0.001	0.601		<0.001		0.241

表1 97例胃癌患者基本临床资料

组别	例数	性别(例)		年龄(岁，±s)	瘤体最大直径(cm，±s)	血管浸润(例)	神经浸润(例)
组别	例数	男	女	年龄(岁，±s)	瘤体最大直径(cm，±s)	血管浸润(例)	神经浸润(例)
PFS组	63	40	25	58.07±7.24	2.56±0.75	21	30
非PFS组	28	16	10	58.31±6.14	2.96±0.85	15	13
统计值		χ²=0.129		t=0.154	t=2.645	χ²=7.569	χ²=0.078
P值		0.719		0.878	0.011	0.005	0.778
组别	淋巴结转移(例)	TWA1 mRNA(±s)	肿瘤位置(例)		TNM分期(例)		术后辅助化疗(例)
组别	淋巴结转移(例)	TWA1 mRNA(±s)	贲门	胃体胃窦	Ⅰ~Ⅱ	Ⅲ~Ⅳ	术后辅助化疗(例)
PFS组	33	1.07±0.26	30	33	43	20	46
非PFS组	24	1.37±0.27	15	13	7	21	17
统计值	χ²=9.203	t=5.003	χ²=0.274		χ²=14.651		χ²=1.377
P值	0.002	<0.001	0.601		<0.001		0.241

表2 影响胃癌患者无进展生存期的Cox回归分析结果

变量	β	SE	Wald	P值	HR	95% CI
性别构成(男vs女)	0.065	0.480	0.018	0.893	1.067	0.416~2.735
年龄(实测值)	0.012	0.030	0.155	0.694	1.012	0.954~1.073
瘤体最大直径(实测值)	0.221	0.273	0.649	0.420	1.246	0.729~2.129
血管浸润(是vs否)	0.298	0.476	0.391	0.532	1.347	0.292~1.886
神经浸润(是vs否)	0.123	0.432	0.081	0.775	1.131	0.485~2.640
淋巴结转移(是vs否)	1.175	0.584	4.040	0.044	3.328	2.098~5.971
TWA1 mRNA(实测值)	2.005	0.749	7.164	0.007	7.429	1.711~32.263
肿瘤位置(贲门vs胃体胃窦)	-0.582	0.435	1.784	0.182	0.559	0.238~1.312
TNM分期(Ⅲ~ⅣvsⅠ~Ⅱ)	1.224	0.484	6.400	0.011	3.400	1.114~4.759
术后辅助化疗(是vs否)	-0.702	0.481	2.126	0.145	0.459	0.785~5.181

表2 影响胃癌患者无进展生存期的Cox回归分析结果

变量	β	SE	Wald	P值	HR	95% CI
性别构成(男vs女)	0.065	0.480	0.018	0.893	1.067	0.416~2.735
年龄(实测值)	0.012	0.030	0.155	0.694	1.012	0.954~1.073
瘤体最大直径(实测值)	0.221	0.273	0.649	0.420	1.246	0.729~2.129
血管浸润(是vs否)	0.298	0.476	0.391	0.532	1.347	0.292~1.886
神经浸润(是vs否)	0.123	0.432	0.081	0.775	1.131	0.485~2.640
淋巴结转移(是vs否)	1.175	0.584	4.040	0.044	3.328	2.098~5.971
TWA1 mRNA(实测值)	2.005	0.749	7.164	0.007	7.429	1.711~32.263
肿瘤位置(贲门vs胃体胃窦)	-0.582	0.435	1.784	0.182	0.559	0.238~1.312
TNM分期(Ⅲ~ⅣvsⅠ~Ⅱ)	1.224	0.484	6.400	0.011	3.400	1.114~4.759
术后辅助化疗(是vs否)	-0.702	0.481	2.126	0.145	0.459	0.785~5.181

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Predictive study of TWA1 mRNA expression in peripheral blood on the prognosis of patients with gastric cancer

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Predictive study of TWA1 mRNA expression in peripheral blood on the prognosis of patients with gastric cancer