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

[1]	Kaito A, Kinoshita T, Tokunaga M, et al. Prognostic factors and recurrence pattern of far-advanced gastric cancer with pathologically-positive para-aortic lymph nodes[J]. Anticancer Res, 2017, 37(7): 3685-3692.
[2]	Allemani C, Matsuda T, Di Carlo V, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries[J]. Lancet, 2018, 391(10125): 1023-1075.
[3]	Yang H, Fu H, Wang B, et al. Exosomal miR-423-5p targets SUFU to promote cancer growth and metastasis and serves as a novel marker for gastric cancer[J]. Mol Carcinog, 2018, 57(9): 1223-1236.
[4]	Francis O, Baker GE, Race PR, et al. Studies of recombinant TWA1 reveal constitutive dimerization[J]. Biosci Rep, 2017, 37(1): pii: BSR20160401.
[5]	Ore F, Fujun H, Adams JC, et al. Molecular phylogeny of a RING E3 Ubiquitin ligase, conserved in eukaryotic cells and dominated by homologous components, the Muskelin/RanBPM/CTLH complex[J]. PLoS One, 2013, 8(10): e75217.
[6]	Lu Y, Xie S, Zhang W, et al. Twa1/Gid8 is a β-catenin nuclear retention factor in Wnt signaling and colorectal tumorigenesis[J]. Cell Res, 2017, 27(12): 1422-1440.
[7]	Smyth EC, Verheij M, Allum W, et al. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up[J]. Ann Oncol, 2016, 27(suppl 5): v38-v49.
[8]	曹一鑫, 李小琴, 王宏宇, 等. Tensin1蛋白与胃癌临床病理特征及预后的关系[J]. 中华消化外科杂志, 2018, 17(6): 612-618.
[9]	de Araujo TS, Almeida MS. 1H, 13C and 15N chemical shift assignment of lissencephaly-1 homology (LisH) domain homodimer of human two-hybrid-associated protein 1 with RanBPM (Twa1)[J]. Biomol NMR Assign, 2018, 12(1): 99-102.
[10]	Huffman N, Palmieri D, Coppola V. The CTLH complex in cancer cell plasticity[J]. J Oncol, 2019, 2019: 4216750.
[11]	Hou G, Yuan X, Li Y, et al. Cardamonin, a natural chalcone, reduces 5-fluorouracil resistance of gastric cancer cells through targeting Wnt/β-catenin signal pathway[J]. Invest New Drugs, 2020, 38(2): 329-339.
[12]	Kilic L, Ordu C, Yildiz I, et al. Current adjuvant treatment modalities for gastric cancer: from history to the future[J]. World J Gastrointest Oncol, 2016, 8(5): 439-449.
[13]	Cheng L, Wang P, Yang S, et al. Identification of genes with a correlation between copy number and expression in gastric cancer[J]. BMC Med Genomics, 2012, 5(1): 14.
[14]	Tessari A, Parbhoo K, Pawlikowski M, et al. RANBP9 affects cancer cells response to genotoxic stress and its overexpression is associated with worse response to platinum in NSCLC patients[J].Oncogene, 2018, 37(50): 6463-6476.
[15]	Jiang F, Shi Y, Lu H, et al. Armadillo repeat-containing protein 8 (ARMC8) silencing inhibits proliferation and invasion in osteosarcoma cells[J]. Oncol Res, 2016, 24(5): 381-389.
[16]	Xiong J, Feng Z, Li Z, et al. Overexpression of TWA1 predicts poor prognosis in patients with gastric cancer[J]. Pathol Res Pract, 2019, 215(11): 152594.

[1]	张思平, 刘伟, 马鹏程. 全膝关节置换术后下肢轻度内翻对线对疗效的影响[J]. 中华关节外科杂志(电子版), 2023, 17(06): 808-817.
[2]	李越洲, 张孔玺, 李小红, 商中华. 基于生物信息学分析胃癌中PUM的预后意义[J]. 中华普通外科学文献(电子版), 2023, 17(06): 426-432.
[3]	张俊, 罗再, 段茗玉, 裘正军, 黄陈. 胃癌预后预测模型的研究进展[J]. 中华普通外科学文献(电子版), 2023, 17(06): 456-461.
[4]	马伟强, 马斌林, 吴中语, 张莹. microRNA在三阴性乳腺癌进展中发挥的作用[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 111-114.
[5]	杨倩, 李翠芳, 张婉秋. 原发性肝癌自发性破裂出血急诊TACE术后的近远期预后及影响因素分析[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 33-36.
[6]	栗艳松, 冯会敏, 刘明超, 刘泽鹏, 姜秋霞. STIP1在三阴性乳腺癌组织中的表达及临床意义研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 52-56.
[7]	江振剑, 蒋明, 黄大莉. TK1、Ki67蛋白在分化型甲状腺癌组织中的表达及预后价值研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 623-626.
[8]	晏晴艳, 雍晓梅, 罗洪, 杜敏. 成都地区老年转移性乳腺癌的预后及生存因素研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 636-638.
[9]	莫波, 王佩, 王恒, 何志军, 梁俊, 郝志楠. 腹腔镜胃癌根治术与改良胃癌根治术治疗早期胃癌的疗效[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 644-647.
[10]	鲁鑫, 许佳怡, 刘洋, 杨琴, 鞠雯雯, 徐缨龙. 早期LC术与PTCD续贯LC术治疗急性胆囊炎对患者肝功能及预后的影响比较[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 648-650.
[11]	陈大敏, 曹晓刚, 曹能琦. 肥胖对胃癌患者手术治疗效果的影响研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 651-653.
[12]	姜明, 罗锐, 龙成超. 闭孔疝的诊断与治疗：10年73例患者诊疗经验总结[J]. 中华疝和腹壁外科杂志(电子版), 2023, 17(06): 706-710.
[13]	李永胜, 孙家和, 郭书伟, 卢义康, 刘洪洲. 高龄结直肠癌患者根治术后短期并发症及其影响因素[J]. 中华临床医师杂志(电子版), 2023, 17(9): 962-967.
[14]	王军, 刘鲲鹏, 姚兰, 张华, 魏越, 索利斌, 陈骏, 苗成利, 罗成华. 腹膜后肿瘤切除术中大量输血患者的麻醉管理特点与分析[J]. 中华临床医师杂志(电子版), 2023, 17(08): 844-849.
[15]	索利斌, 刘鲲鹏, 姚兰, 张华, 魏越, 王军, 陈骏, 苗成利, 罗成华. 原发性腹膜后副神经节瘤切除术麻醉管理的特点和分析[J]. 中华临床医师杂志(电子版), 2023, 17(07): 771-776.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

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

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

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