The expression of VASP in colorectal cancer and its relationship with metastasis

doi:10.3877/cma.j.issn.2095-3224.2021.03.008

Abstract

Abstract:

Objective

We analyze the expression of VASP in CRC, and study the role of VASP in promoting CRC metastasis.

Methods

The expression of VASP was detected by Real-time PCR and immunohistochemistry in human CRC cohort. The effect of VASP-mediated invasion and metastasis were analyzed by Transwell assays and tail veins metastasis model both in vitro and in vivo.

Results

The expression levels of VASP were dramatically higher in CRC tissues than in adjacent nontumor tissues (χ²=82.1,P＜0.001). Elevated expression of VASP was positively correlated with tumor size, tumor differentiation, nerve invasion, the lymph node metastasis, distant metastasis, higher American Joint Committee on Cancer (AJCC stage) and poor prognosis in human CRC. COX analysis indicated VASP expression was independent predictor for high recurrence rate and poor overall survival. Elevated expression of VASP promotes CRC metastasis both in vitro and in vivo.

Conclusion

VASP was overexpression and correlated with poor prognosis in CRC. Upregulated VASP can promote CRC metastasis and could be served as a potential treatment marker for CRC patients.

Key words: Colorectalneoplasms, VASP, Invasion, Metastasis

Yunzhi Dang, Jiao Yu, Shuhong Zhao, Long Jin, Xiaoyue Ren, Qing Wang. The expression of VASP in colorectal cancer and its relationship with metastasis[J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2021, 10(03): 266-272.

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https://zhjzcjbdzzz.cma-cmc.com.cn/EN/Y2021/V10/I03/266

Figures/Tables 5

References 19

1	Freddie B, Jacques F, Isabelle S, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424.
2	Fakih GM, Metastatic colorectal cancer: current state and future directions[J]. J Clin Oncol, 2015. 33(16): 1809-1824.
3	Jemal A, Siege R, Ward E, et al. Cancer statistics, 2008[J]. CA Cancer J Clin, 2008. 58(2): 71-96.
4	Punt CJ, Koopman M, Vermeulen L, et al. From tumour heterogeneity to advances in precision treatment of colorectal cancer[J]. Nat Rev Clin Oncol, 2017, 14(4): 235-246.
5	Shami K, Kevin CO, Nicole LE, et al. American cancer society colorectal cancer survivorship care guidelines[J]. CA Cancer J Clin, 2015, 65(6): 428-455.
6	Krause M, Erik WD, James EB, et al. Ena/VASP proteins: regulators of the actin cytoskeleton and cell migration[J]. Annu Rev Cell Dev Biol, 2003, 19: 541-564.
7	Dennis B, Antje KK, Joern K, et al. Molecular mechanism of Ena/VASP-mediated actin-filament elongation[J]. EMBO J, 2011, 30(3): 456-467.
8	Chen XJ, Anna JS, Raiko S, et al. Ena/VASP proteins cooperate with the WAVE complex to regulate the actin cytoskeleton[J]. Dev Cell, 2014, 30(5): 569-584.
9	Tu KS, Li JC, Liu CS, et al. Vasodilator-stimulated phosphoprotein promotes activation of hepatic stellate cells by regulating Rab11-dependent plasma membrane targeting of transforming growth factor beta receptors[J]. Hepatology, 2015, 61(1): 361-374.
10	Wang J, Zhang J, Wu J, et al. MicroRNA-610 inhibits the migration and invasion of gastric cancer cells by suppressing the expression of vasodilator-stimulated phosphoprotein[J]. Eur J Cancer, 2012, 48(12): 1904-1913.
11	Carmona G, Perera U, Gillett C, et al. Lamellipodin promotes invasive 3D cancer cell migration via regulated interactions with Ena/VASP and SCAR/WAVE[J]. Oncogene, 2016, 35(39): 5155-5169.
12	Liu ZK, Wang YF, Dou CW, et al. Hypoxia-induced up-regulation of VASP promotes invasiveness and metastasis of hepatocellular carcinoma[J]. Theranostics, 2018, 8(17): 4649-4663.
13	Li K, Zhang J, Tian Y, et al. The Wnt/β-catenin/VASP positive feedback loop drives cell proliferation and migration in breast cancer[J]. Oncogene, 2020, 39(11): 2258-2274.
14	Dang YZ, Chen J, Feng WB, et al. Interleukin 1β-mediated HOXC10 overexpression promotes hepatocellular carcinoma metastasis by upregulating PDPK1 and VASP[J]. Theranostics, 2020, 10(8): 3833-3848.
15	Huang F, Ma G, Zhou X, et al. Depletion of LAMP3 enhances PKA-mediated VASP phosphorylation to suppress invasion and metastasis in esophageal squamous cell carcinoma[J]. Cancer Lett, 2020, 479: 100-111.
16	田耀文, 霍婷婷, 王东旭, 等. 结直肠癌同时性肝外转移相关临床病理因素分析[J]. 中华肿瘤防治杂志, 2018, 25(2): 135-139.
17	Pitari GM, Cotzia P, Ali M, et al. Vasodilator-stimulated phosphoprotein biomarkers are associated with invasion and metastasis in colorectal cancer[J]. Biomark Cancer, 2018, 10: 1179299X18774551.
18	宋胜江, 孙利敏, 徐定银, 等. VASP在结肠癌组织中的表达及其对预后的影响[J]. 实用肿瘤杂志, 2016, 31(1): 48-52.
19	陈晨, 金旭, 翁稚颖, 等. PKG、PKA及VASP在人结直肠癌组织中的表达及临床意义[J]. 重庆医学, 2019, 48(10): 1669-1673.

临床参数	VASP的表达		χ²值	P值
临床参数	阴性（n=137）	阳性（n=85）	χ²值	P值
年龄（岁）			0.769	0.381
≤60	30	23
＞60	107	62
性别			0.403	0.525
女	64	36
男	73	49
肿瘤大小（cm）			5.134	0.023
≤5	68	29
>5	69	56
肿瘤分化			14.78	＜0.001
高分化或中分化	109	47
低分化	28	38
肿瘤浸润			0.361	0.548
T1~T2	11	5
T3~T4	126	80
脉管侵犯			0.473	0.492
无	104	61
有	33	24
神经侵犯			13.2	＜0.001
无	110	49
有	27	36
淋巴结转移			29.3	＜0.001
无	96	28
有	41	57
远处转移			6.58	0.010
无	120	63
有	17	22
AJCC分期			18.04	＜0.001
I~II	93	33
III~IV	44	52

临床参数	VASP的表达		χ²值	P值
临床参数	阴性（n=137）	阳性（n=85）	χ²值	P值
年龄（岁）			0.769	0.381
≤60	30	23
＞60	107	62
性别			0.403	0.525
女	64	36
男	73	49
肿瘤大小（cm）			5.134	0.023
≤5	68	29
>5	69	56
肿瘤分化			14.78	＜0.001
高分化或中分化	109	47
低分化	28	38
肿瘤浸润			0.361	0.548
T1~T2	11	5
T3~T4	126	80
脉管侵犯			0.473	0.492
无	104	61
有	33	24
神经侵犯			13.2	＜0.001
无	110	49
有	27	36
淋巴结转移			29.3	＜0.001
无	96	28
有	41	57
远处转移			6.58	0.010
无	120	63
有	17	22
AJCC分期			18.04	＜0.001
I~II	93	33
III~IV	44	52

临床参数	复发时间		总体生存时间
临床参数	HR（95% CI）	P值	HR（95% CI）	P值
单因素分析
年龄（≤60 vs. ＞60）	0.937（0.666~1.317）	0.707	0.942（0.670~1.324）	0.729
性别（女vs.男）	0.881（0.627~1.238）	0.465	0.913（0.650~1.284）	0.603
肿瘤大小（≤5 cm vs.＞5 cm）	1.304（0.921~1.845）	0.135	0.739（0.522~1.047）	0.089
肿瘤分化（高/中vs.差）	0.165（0.115~0.238）	＜0.001	0.156（0.108~0.225）	＜0.001
肿瘤浸润（Ⅰ~Ⅱ vs. Ⅲ）	0.290（0.20~0.422）	＜0.001	0.296（0.204~0.403）	＜0.001
脉管侵犯（无vs.有）	0.704（0.480~1.032）	0.072	0.671（0.46~0.98）	0.040
神经侵犯（无vs.有）	0.879（0.605~1.28）	0.50	0.837（0.58~1.21）	0.35
治疗方式（单纯手术vs.手术+放疗/化疗）	0.278（0.19~0.39）	＜0.001	0.273（0.18~0.36）	＜0.001
淋巴结转移（无vs.有）	0.0960（0.063~0.146）	＜0.001	0.096（0.064~0.146）	＜0.001
远处转移（无vs.有）	0.098（0.062~0.153）	＜0.001	0.101（0.065~0.156）	＜0.001
VASP表达（无vs.有）	0.252（0.176~0.360）	＜0.001	0.249 （0.177~0.3627）	＜0.001
多因素分析
肿瘤分化（好/中 vs.差）	0.857（0.532~1.381）	0.526	0.797（0.493~1.288）	0.354
肿瘤浸润（Ⅰ~Ⅱ vs. Ⅲ~Ⅳ）	0.558（0.278~1.119）	0.10	0.854（0.562~1.296）	0.457
淋巴结转移（无 vs. 有）	0.291（0.156~0.542）	＜0.001	0.266（0.142~0.498）	＜0.001
脉管侵犯（无 vs.有）	0.681（0.457~1.014）	0.058	0.689（0.463~1.025）	0.066
神经侵犯（无 vs.有）	1.317（0.877~1.979）	0.184	1.223（0.814~1.836）	0.333
治疗方式（单纯手术 vs.手术+放疗/化疗）	0.835（0.550~1.266）	0.395	0.854（0.562~1.296）	0.457
远处转移（无 vs. 有）	0.233（0.137~0.396）	＜0.001	0.261（0.157~0.435）	＜0.001
AJCC分期（Ⅰ~Ⅱ vs. Ⅲ）	0.525（0.314~0.877）	0.014	0.578（0.343~0.973）	0.039
VASP表达（阴性 vs. 阳性）	0.402（0.267~0.604）	＜0.001	0.476（0.316~0.715）	＜0.001

临床参数	复发时间		总体生存时间
临床参数	HR（95% CI）	P值	HR（95% CI）	P值
单因素分析
年龄（≤60 vs. ＞60）	0.937（0.666~1.317）	0.707	0.942（0.670~1.324）	0.729
性别（女vs.男）	0.881（0.627~1.238）	0.465	0.913（0.650~1.284）	0.603
肿瘤大小（≤5 cm vs.＞5 cm）	1.304（0.921~1.845）	0.135	0.739（0.522~1.047）	0.089
肿瘤分化（高/中vs.差）	0.165（0.115~0.238）	＜0.001	0.156（0.108~0.225）	＜0.001
肿瘤浸润（Ⅰ~Ⅱ vs. Ⅲ）	0.290（0.20~0.422）	＜0.001	0.296（0.204~0.403）	＜0.001
脉管侵犯（无vs.有）	0.704（0.480~1.032）	0.072	0.671（0.46~0.98）	0.040
神经侵犯（无vs.有）	0.879（0.605~1.28）	0.50	0.837（0.58~1.21）	0.35
治疗方式（单纯手术vs.手术+放疗/化疗）	0.278（0.19~0.39）	＜0.001	0.273（0.18~0.36）	＜0.001
淋巴结转移（无vs.有）	0.0960（0.063~0.146）	＜0.001	0.096（0.064~0.146）	＜0.001
远处转移（无vs.有）	0.098（0.062~0.153）	＜0.001	0.101（0.065~0.156）	＜0.001
VASP表达（无vs.有）	0.252（0.176~0.360）	＜0.001	0.249 （0.177~0.3627）	＜0.001
多因素分析
肿瘤分化（好/中 vs.差）	0.857（0.532~1.381）	0.526	0.797（0.493~1.288）	0.354
肿瘤浸润（Ⅰ~Ⅱ vs. Ⅲ~Ⅳ）	0.558（0.278~1.119）	0.10	0.854（0.562~1.296）	0.457
淋巴结转移（无 vs. 有）	0.291（0.156~0.542）	＜0.001	0.266（0.142~0.498）	＜0.001
脉管侵犯（无 vs.有）	0.681（0.457~1.014）	0.058	0.689（0.463~1.025）	0.066
神经侵犯（无 vs.有）	1.317（0.877~1.979）	0.184	1.223（0.814~1.836）	0.333
治疗方式（单纯手术 vs.手术+放疗/化疗）	0.835（0.550~1.266）	0.395	0.854（0.562~1.296）	0.457
远处转移（无 vs. 有）	0.233（0.137~0.396）	＜0.001	0.261（0.157~0.435）	＜0.001
AJCC分期（Ⅰ~Ⅱ vs. Ⅲ）	0.525（0.314~0.877）	0.014	0.578（0.343~0.973）	0.039
VASP表达（阴性 vs. 阳性）	0.402（0.267~0.604）	＜0.001	0.476（0.316~0.715）	＜0.001

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