干性相关分子Nanog在食管鳞状细胞癌组织中高表达并促进食管鳞癌细胞的侵袭转移：基于激活TGF-β信号通路

doi:10.12122/j.issn.1673-4254.2024.06.23

南方医科大学学报 ›› 2024, Vol. 44 ›› Issue (6): 1209-1216.doi: 10.12122/j.issn.1673-4254.2024.06.23

• • 上一篇

干性相关分子Nanog在食管鳞状细胞癌组织中高表达并促进食管鳞癌细胞的侵袭转移：基于激活TGF-β信号通路

孙畅¹(), 郑士耀¹^,³, 李梅¹^,⁴, 杨铭¹, 秦梦园¹, 徐媛¹, 梁伟华¹, 胡建明¹, 王良海¹, 李锋¹^,², 周虹⁵, 杨兰¹()

^1.石河子大学医学院病理系//石河子大学第一附属医院病理科，新疆维吾尔自治区 ;石河子 832000
^2.首都医科大学附属北京朝阳医院病理科，北京 100000
^3.乳山市人民医院病理科，山东威海 264200
^4.烟台市莱阳中心医院病理科，山东烟台 264000
^5.澳大利亚悉尼大学ANZAC研究所，悉尼 2050

收稿日期:2023-10-11 出版日期:2024-06-20 发布日期:2024-07-01
通讯作者: 杨兰 E-mail:sunchangyysw@163.com;yl-branda@163.com
作者简介:孙畅，在读硕士研究生，E-mail: sunchangyysw@163.com
基金资助:
国家自然科学基金(81860518);石河子大学国际科技合作推进计划项目(GJHZ202105);兵团重点癌症早诊早治项目(CZ002907)

High expression of the stemness-associated molecule Nanog in esophageal squamous cell carcinoma tissues promotes tumor invasion and metastasis by activating the TGF‑β signaling pathway

Chang SUN¹(), Shiyao ZHENG¹^,³, Mei LI¹^,⁴, Ming YANG¹, Mengyuan QIN¹, Yuan XU¹, Weihua LIANG¹, Jianmin HU¹, Lianghai WANG¹, Feng LI¹^,², Hong ZHOU⁵, Lan YANG¹()

^1.Department of Pathology, Department of Pathology of First Affiliated Hospital, Shihezi University School of Medicine, Shihezi 832000, China
^2.Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100000, China
^3.Department of Pathology, Rushan People's Hospital, Weihai 264200, China
^4.Department of Pathology, Laiyang Central Hospital, Yantai 264000, China
^5.ANZAC Research Institute, University of Sydney, Sydney 2050, Australia

Received:2023-10-11 Online:2024-06-20 Published:2024-07-01
Contact: Lan YANG E-mail:sunchangyysw@163.com;yl-branda@163.com
Supported by:
Natural Science Foundation of China(81860518)

摘要/Abstract

摘要：

目的探讨食管鳞状细胞癌（鳞癌）中干性相关分子胚胎干细胞关键因子（Nanog）和侵袭迁移相关分子基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）蛋白的表达及其之间的调控关系。方法运用免疫组织化学技术检测127例食管鳞癌组织和82例癌旁正常组织中Nanog和MMP-2/MMP-9蛋白的表达情况，分析Nanog和MMP-2/MMP-9蛋白的表达水平、相关性及与食管鳞癌患者的临床病理参数和预后之间的关系；采用GEO数据库分析Nanog等干性相关分子主要富集通路；应用TIMER在线网站分析食管癌中TβR1和MMP-2及MMP-9的相关性。在体外运用siRNA转染的方式将食管鳞癌细胞株分为正常对照组、Nanog低表达组，采用划痕实验分析其对食管鳞癌细胞迁移的影响，qRT-PCR及Western blotting检测两组之间TβR1、p-Smad2/3、MMP-2/MMP-9的表达情况。结果 Nanog和MMP-2/MMP-9蛋白在食管鳞癌组织中表达均上调（χ²=70.475，P<0.01；χ²=34.415，P<0.01；χ²=46.605，P<0.01），且呈正相关（r=0.205，P=0.045；r=0.307，P<0.001）。Nanog和MMP-2/MMP-9蛋白表达水平与食管鳞癌的浸润深度相关（χ²=23.9，P<0.01；χ²=6.029，P<0.05；χ²=11.89，P<0.05），有淋巴结转移的样本中，MMP-2/MMP-9蛋白表达水平高于无淋巴结转移的样本（χ²=10.08，P<0.01；χ²=5.731，P<0.05）。MMP-2/MMP-9蛋白表达与食管鳞癌患者的年龄、性别和肿瘤分化程度无相关性（P>0.05）。Kaplan-Meier生存分析显示，Nanog和MMP-2/MMP-9蛋白高表达组的食管鳞癌患者生存时间短于低表达组（P<0.001；P=0.004；P=0.017）；生物信息学分析显示，Nanog等干性相关分子主要富集在转化生长因子-β（TGF-β）信号通路，MMP-2/MMP-9与TβR1表达在食管癌中呈正相关关系。体外划痕实验结果显示，Nanog促进食管鳞癌细胞系的迁移；qRT-PCR及Western blotting结果显示，敲低Nanog后，TβR1、p-Smad2/3、MMP-2/MMP-9的表达水平明显降低。结论 Nanog和MMP-2/MMP-9蛋白在食管鳞癌患者组织中高表达且呈正相关，其与食管鳞癌患者的肿瘤浸润深度、淋巴结转移及预后密切相关，且Nanog通过TGF-β信号通路影响MMP-2/MMP-9蛋白的表达。

关键词: 食管鳞状细胞癌, 胚胎干细胞关键因子, 基质金属蛋白酶-2/基质金属蛋白酶-9, 浸润转移, 生存分析

Abstract:

Objective To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma (ESCC). Methods We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients. GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog, and TIMER online tool was used to analyze the correlations among TβR1, MMP-2, and MMP-9 in esophageal cancer. Results Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated. Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age, gender, or tumor differentiation. The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time. Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway, and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated. In cultured ESCC cells, Nanog knockdown significantly decreased the expression of TβR1, p-Smad2/3, MMP-2, and MMP-9 and strongly inhibited cell migration. Conclusion The high expressions of Nanog, MMP-2, and MMP-9, which are positively correlated, are closely related with invasion depth, lymph node metastasis, and prognosis of ESCC. Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF‑β signaling pathway, and its high expression promotes migration of ESCC cells.

Key words: esophageal squamous cell carcinoma, Nanog, MMP-2/MMP-9, infiltration and metastasis, survival analysis

孙畅, 郑士耀, 李梅, 杨铭, 秦梦园, 徐媛, 梁伟华, 胡建明, 王良海, 李锋, 周虹, 杨兰. 干性相关分子Nanog在食管鳞状细胞癌组织中高表达并促进食管鳞癌细胞的侵袭转移：基于激活TGF-β信号通路[J]. 南方医科大学学报, 2024, 44(6): 1209-1216.

Chang SUN, Shiyao ZHENG, Mei LI, Ming YANG, Mengyuan QIN, Yuan XU, Weihua LIANG, Jianmin HU, Lianghai WANG, Feng LI, Hong ZHOU, Lan YANG. High expression of the stemness-associated molecule Nanog in esophageal squamous cell carcinoma tissues promotes tumor invasion and metastasis by activating the TGF‑β signaling pathway[J]. Journal of Southern Medical University, 2024, 44(6): 1209-1216.

图/表 10

表1 127例食管癌患者的临床病理特征

Tab.1 Clinical and pathological characteristics of 127 esophageal cancer patients

Clinicopathological parameters	n	Percentage (%)
Age (year)
<60	73	57.48
≥60	54	42.52
Gender
Male	78	61.42
Female	49	38.58
Differentiation
High	40	31.5
Medium	72	56.69
Low	15	11.81
T stage
T1	16	12.6
T2	52	40.94
T3-T4	40	46.46
Lymph node metastasis
+	84	66.14
－	43	33.86

图1 食管鳞癌组织及癌旁正常组织中Nanog、MMP-2及MMP-9蛋白免疫组化染色结果

Fig.1 Immunohistochemical staining of Nanog, MMP-2, and MMP-9 proteins in esophageal squamous cell carcinoma tissues and adjacent normal tissues. A: Negative expression of Nanog in adjacent normal tissues. B: Weak positive expression (1+) of Nanog in esophageal squamous cell carcinoma tissues. C: Moderate positive expression (2+) of Nanog in esophageal squamous cell carcinoma tissues. D: Strong positive expression (3+) of Nanog in esophageal squamous cell carcinoma tissues. E: Negative expression of MMP-2 in adjacent normal tissues. F: Weak positive expression (1+) of MMP-2 in esophageal squamous cell carcinoma tissues. G: Moderate positive expression (2+) of MMP-2 in esophageal squamous cell carcinoma tissues. H: Strong positive expression (3+) of MMP-2 in esophageal squamous cell carcinoma tissues. I: Negative expression (-) of MMP-9 in adjacent normal tissues. J: Weak positive expression (1+) of MMP-9 in esophageal squamous cell carcinoma tissues. K: Moderate positive expression (2+) of MMP-9 in esophageal squamous cell carcinoma tissues. L: Strong positive expression (3+) of MMP-9 in esophageal squamous cell carcinoma tissues.

表2 食管鳞癌及癌旁组织中Nanog、MMP-2及MMP-9蛋白的表达情况

Tab.2 Expression of Nanog, MMP-2 and MMP-9 protein in esophageal squamous cell carcinoma and adjacent tissues

Protein	Tissue samples	n	High expression	Low expression	χ²	P
Nanog	ESCC tissue	122	79	43	70.475	<0.01
Nanog	paraneoplastic tissue	79	4	75
MMP-2	ESCC tissue	99	58	41	35.415	<0.01
MMP-2	paraneoplastic tissue	73	10	63
MMP-9	ESCC tissue	119	60	59	46.605	<0.01
MMP-9	paraneoplastic tissue	81	3	78

表3 Nanog、MMP-2、MMP-9蛋白表达与食管鳞癌患者临床病理参数

Tab.3 Clinical-pathological parameters of patients with esophageal squamous cell carcinoma having high or low Nanog, MMP-2 and MMP-9 protein expressions

Clinicopathological parameters	Nanog			χ²	P	MMP-2			χ²	P	MMP-9			χ²	P
Clinicopathological parameters	n	High expression	Low expression	χ²	P	n	High expression	Low expression	χ²	P	n	High expression	Low expression	χ²	P
Gender
Male	76	50	26	0.095	0.758	57	31	26	0.977	0.41	69	35	34	0.006	1.000
Female	46	29	17			42	27	15			50	25	25
Age (year)
<60	70	45	25	0.016	0.900	60	40	20	4.099	0.060	72	37	35	0.068	0.852
≥60	52	34	18			39	18	21			47	23	24
T stage
T1	15	2	13	23.90	<0.01	8	2	6	6.029	0.049	14	1	13	11.89	0.003
T2	50	31	19			45	31	14			50	28	22
T3-T4	57	46	11			46	25	21			55	31	24
Lymph node metastasis
+	80	55	25	1.626	0.202	66	46	20	10.08	0.020	79	46	33	5.731	0.020
－	42	24	18			33	12	21			40	14	26
Differentiation
High	36	19	17	5.483	0.064	31	18	13	0.268	0.875	13	6	7	2.534	0.282
Medium	71	47	24			59	34	25			67	38	29
Low	15	13	2			9	6	3			39	16	23

图2 Nanog、MMP-2及MMP-9蛋白表达水平与食管鳞癌患者术后生存时间关系的生存曲线

Fig.2 Postoperative survival curves of esophageal squamous cell carcinoma patients with low and high Nanog, MMP-2 and MMP-9 protein expressions. A: Survival curves of patients with high and low Nanog expressions (P<0.001). B: Survival curves of patients with high and low MMP-2 protein expression (P=0.004). C: Survival curves of patients with high and low MMP-9 protein expressions (P=0.017).

表4 食管癌中Nanog蛋白表达与侵袭迁移相关蛋白表达的相关性

Tab.4 Correlation between expressions of Nanog and invasion- and migration-related proteins in esophageal cancer

Nanog	MMP-2			r	P	MMP-9			r	P
Nanog	n	High expression	Low expression	r	P	n	High expression	Low expression	r	P
High expression	66	43	23	0.205	0.045	74	46	28	0.307	0.001
Low expression	30	13	17			40	12	28

图3 生物信息学分析

Fig.3 Bioinformatics analysis. A: KEGG pathway enrichment analysis of differentially expressed genes in the gene chip dataset GSE13834. B: Scatter plot showing the correlation between TβR1 and MMP-2 expression in esophageal cancer. C: Scatter plot showing the correlation between TβR1 and MMP-9 expression in esophageal cancer.

表5 食管癌中Nanog、MMP-2及MMP-9蛋白表达与TGFβ信号通路相关蛋白表达的相关性

Tab.5 Correlation of Nanog, MMP-2 and MMP-9 protein expressions with expressions of TGF-β signaling pathway proteins in ESCC

Protein			TβR1		r	P		p-Smad2/3		r	P
Protein		n High expression		Low expression	n High expression		Low expression
Nanog	High expression	68	50	18	0.318	0.001	68	50	18	0.301	0.002
Nanog	Low expression	32	13	19			35	15	20
MMP-2	High expression	56	47	9	0.448	<0.001	52	40	12	0.303	0.004
MMP-2	Low expression	47	18	29			55	27	28
MMP-9	High expression	53	39	14	0.202	0.045	54	40	14	0.239	0.015
MMP-9	Low expression	50	26	24			51	27	24

图4 Nanog基因敲低对食管鳞癌细胞体外迁移的影响

Fig.4 Effect of Nanog knockdown on migration of esophageal squamous cell carcinoma cells. A: qRT-PCR of Nanog mRNA expression levels after Nanog knockdown (P<0.05). B: Western blotting of Nanog protein expression after Nanog knockdown. C: Scratch assay for assessing changes in migration ability of TE-1 cells after Nanog knockdown. *P˂0.05, **P˂0.01 vs NC group.

图5 敲低Nanog后TGF-β信号通路及侵袭迁移相关分子表达

Fig.5 Expression of TGF-β signaling pathway and invasion- and migration-related molecules after Nanog knockdown. A: qRT-PCR of TβR1, Smad2, MMP-2, and MMP-9 mRNA levels after Nanog knockdown. B: Western blotting of TβR1, p-Smad2/3, MMP-2, and MMP-9 protein levels after Nanog knockdown. *P˂0.05, **P˂0.01, ***P<0.001 vs NC group.

参考文献 26

1	郑荣寿, 陈茹, 韩冰峰, 等. 2022年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2024, 46(3): 221-31. DOI: 10.3760/cma.j.cn112152-20240119-00035
2	Zeng HM, Chen WQ, Zheng RS, et al. Changing cancer survival in China during 2003-15: a pooled analysis of 17 population-based cancer registries[J]. Lancet Glob Health, 2018, 6(5): e555-67.
3	Nafteux PR, Lerut AM, Moons J, et al. International multicenter study on the impact of extracapsular lymph node involvement in primary surgery adenocarcinoma of the esophagus on overall survival and staging systems[J]. Ann Surg, 2015, 262(5): 809-15.
4	Zhu ZP, Xu JH, Li LL, et al. Effect of gastric cancer stem cell on gastric cancer invasion, migration and angiogenesis[J]. Int J Med Sci, 2020, 17(13): 2040-51.
5	Li D, Peng XQ, He GP, et al. Crosstalk between autophagy and CSCs: molecular mechanisms and translational implications[J]. Cell Death Dis, 2023, 14(7): 409-13.
6	Pádua D, Figueira P, Ribeiro I, et al. The relevance of transcription factors in gastric and colorectal cancer stem cells identification and eradication[J]. Front Cell Dev Biol, 2020, 8: 442-9.
7	Vasefifar P, Motafakkerazad R, Maleki LA, et al. Nanog, as a key cancer stem cell marker in tumor progression[J]. Gene, 2022, 827: 146448-57.
8	Deng L, Zhang XP, Xiang XC, et al. NANOG promotes cell proliferation, invasion, and stemness via IL-6/STAT3 signaling in esophageal squamous carcinoma[J]. Technol Cancer Res Treat, 2021, 20: 11038492-56.
9	Serej ZA, Ebrahimi A, Kazemi T, et al. NANOG gene suppression and replacement of let-7 modulate the stemness, invasion, and apoptosis in breast cancer[J]. Gene, 2021, 801: 145844-53.
10	Vasefifar P, Najafi S, Motafakkerazad R, et al. Targeting Nanog expression increased Cisplatin chemosensitivity and inhibited cell migration in Gastric cancer cells[J]. Exp Cell Res, 2023, 429(2): 113681-8.
11	Samantaray S, Sharma R, Chattopadhyaya TK, et al. Increased expression of MMP-2 and MMP-9 in esophageal squamous cell carcinoma[J]. J Cancer Res Clin Oncol, 2004, 130(1): 37-44.
12	Ma K, Zhang C, Li WY. Gamabufotalin suppressed osteosarcoma stem cells through the TGF‑β/periostin/PI3K/AKT pathway[J]. Chem Biol Interact, 2020, 331: 109275-83.
13	杨铭, 李梅, 孙畅, 等. TβR1和p-Smad2/3蛋白在哈萨克族食管鳞状细胞癌中的表达及临床意义[J]. 华中科技大学学报: 医学版, 2023, 52(2): 239-44.
14	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-49.
15	Nimmakayala RK, Leon F, Rachagani S, et al. Metabolic programming of distinct cancer stem cells promotes metastasis of pancreatic ductal adenocarcinoma[J]. Oncogene, 2021, 40(1): 215-31.
16	Giri A, Kar S. Interlinked bi-stable switches govern the cell fate commitment of embryonic stem cells[J]. FEBS Lett, 2024, 598(8): 915-34.
17	Rodrigues MFSD, Xavier FCA, Andrade NP, et al. Prognostic implications of CD44, NANOG, OCT4, and BMI1 expression in tongue squamous cell carcinoma[J]. Head Neck, 2018, 40(8): 1759-73.
18	Abdelbary AM, Atwa HA, Elfarargy OM, et al. Prognostic implications of CD24, SOX2, and nanog expression in invasive urothelial carcinoma[J]. Appl Immunohistochem Mol Morphol, 2023, 31(6): 421-8.
19	李秀娟, 赵轶峰, 李明霞, 等. 食管鳞癌组织Nanog表达临床意义分析[J]. 中华肿瘤防治杂志, 2014, 21(24): 1962-5.
20	Stillebroer AB, Mulders PF, Boerman OC, et al. Carbonic anhydrase IX in renal cell carcinoma: implications for prognosis, diagnosis, and therapy[J]. Eur Urol, 2010, 58(1): 75-83.
21	Kashyap T, Nath N, Mishra P, et al. Pluripotency transcription factor Nanog and its association with overall oral squamous cell carcinoma progression, cisplatin-resistance, invasion and stemness acquisition[J]. Head Neck, 2020, 42(11): 3282-94.
22	Alaseem A, Alhazzani K, Dondapati P, et al. Matrix Metallo-proteinases: a challenging paradigm of cancer management[J]. Semin Cancer Biol, 2019, 56: 100-15.
23	Knapinska AM, Fields GB. The expanding role of MT1-MMP in cancer progression[J]. Pharmaceuticals, 2019, 12(2): 77-85.
24	Gobin E, Bagwell K, Wagner J, et al. A pan-cancer perspective of matrix metalloproteases (MMP) gene expression profile and their diagnostic/prognostic potential[J]. BMC Cancer, 2019, 19(1): 581-7.
25	Liu CM, Sheng MX, Lin LH, et al. NANOG regulates the proliferation of PCSCs via the TGF‑β1/SMAD pathway[J]. Open Med, 2020, 15(1): 841-9.
26	Muscella A, Vetrugno C, Cossa LG, et al. TGF-β1 activates RSC96 Schwann cells migration and invasion through MMP-2 and MMP-9 activities[J]. J Neurochem, 2020, 153(4): 525-38.

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干性相关分子Nanog在食管鳞状细胞癌组织中高表达并促进食管鳞癌细胞的侵袭转移：基于激活TGF-β信号通路

High expression of the stemness-associated molecule Nanog in esophageal squamous cell carcinoma tissues promotes tumor invasion and metastasis by activating the TGF‑β signaling pathway

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