GSTO1在卵巢癌组织中的表达及其N-糖基化位点突变对上皮性卵巢癌细胞生物学行为的影响

doi:10.13481/j.1671-587X.20260219

Abstract

Abstract:

Objective To discuss the expression of glutathione S-transferase Omega-1 protein （GSTO1） in epithelial ovarian cancer （EOC） tissue and its relationship with the clinicopathological characteristics and prognosis of the patients， and to investigate the effect of its N-glycosylation modification on the biological behaviors of ovarian cancer A2780 and SKOV3 cells， and to clarify its possible mechanism. Methods GENT2 database was used to analyze the expression levels of GSTO1 mRNA in ovarian cancer tissue and normal ovarian epithelial tissue. The clinical information of 88 EOC patients who visited and underwent surgery in the Department of Gynecology of the First Affiliated Hospital of Shihezi University was collected， the tissue samples were collected， and the prognosis of the patients was followed up regularly. Immunohistochemical method was used to detect the expression of GSTO1 protein in ovarian tissue of EOC patients， and its relationship with the clinicopathological characteristics and prognosis of the patients was analyzed. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors affecting the prognosis of EOC patients. Mass spectrometry was used to compare the difference in N-glycosylation modification of GSTO1 protein between highly metastatic ovarian cancer ES-2 cells and parental SKOV3 cells， and NetNGlyc 1.0 server database was used to identify its modification sites. Tunicamycin was used to inhibit the overall N-glycosylation of cells， and ovarian cancer A2780 and SKOV3 cells were divided into control group， dimethyl sulfoxide （DMSO） group， and tunicamycin group. The ovarian cancer A2780 and SKOV3 cells with different levels of N-glycosylation modification were stably constructed by lentiviral transfection and divided into NC group， WT group， N55Q group， N135Q group， N190Q group， and N3Q group. 5-Ethynyl-2'-deoxyuridine （EdU） assay was used to detect the proliferation rates of the cells in various groups； Transwell chamber assay was used to detect the numbers of migration cells and invasion cells in various groups； Western blotting method was used to detect the expression levels of GSTO1 protein and epithelial-mesenchymal transition （EMT）-related proteins E-cadherin， N-cadherin， and Vimentin in the cells in various groups. Results According to GENT2 database， compared with normal ovarian epithelial tissue， the expression level of GSTO1 mRNA in ovarian cancer tissue was significantly increased （P<0.01）. Immunohistochemical staining results showed that there were 66 cases with high expression of GSTO1 and 22 cases with low expression of GSTO1 in tumor tissues of EOC patients.The high expression of GSTO1 protein in tumor tissue of EOC patients was associated with FIGO stage， lymphovascular space invasion， and tumor diameter （P<0.05）. The univariate and multivariate Cox regression analyses results showed that high FIGO stage， lymph node metastasis， and high GSTO1 expression were independent risk factors affecting the overall survival （OS） and progression-free survival （PFS） of EOC patients. The mass spectrometry results showed that compared with parental SKOV3 cells， the level of N-glycosylation modification of GSTO1 in highly metastatic ovarian cancer ES-2 cells was significantly increased （P<0.05）， and its N-glycosylation modification sites were Asn55， Asn135， and Asn190， respectively. Compared with control group， the expression levels of GSTO1 protein in A2780 and SKOV3 cells in tunicamycin group were significantly decreased （P<0.05）. Compared with WT group， the expression levels of GSTO1 protein in A2780 and SKOV3 cells in N135Q， N190Q， and N3Q groups were significantly decreased （P<0.05）. Compared with WT group， the proliferation rates of A2780 and SKOV3 cells in N135Q， N190Q， and N3Q groups were significantly decreased （P<0.05）. Compared with WT group， the numbers of migration cells and invasion cells of A2780 and SKOV3 cells in N55Q， N135Q， N190Q， and N3Q groups were significantly decreased （P<0.05）. Compared with WT group， the expression levels of E-cadherin protein in A2780 and SKOV3 cells in N3Q group were significantly increased （P<0.05）， and the expression levels of N-cadherin protein and Vimentin protein in A2780 and SKOV3 cells in N190Q and N3Q groups were significantly decreased （P<0.05）. Conclusion GSTO1is highly expressed in EOC tissue and cells and is associated with poor prognosis of patients. Mutation of its N-glycosylation sites can inhibit the proliferation， migration， invasion， and EMT process of ovarian cancer cells.

Key words: Epithelial ovarian cancer, Glutathione S-transferase Omega-1 protein, N-glycosylation, Cell migration, Cell invasion, Cell proliferation, Epithelial-mesenchymal transition

CLC Number:

R737.33

Hong LI,Panpan YU,Zouyu ZHAO,Chongfeng SUN,Hui QIAO,Ping YANG. Expression of GSTO1 in ovarian cancer tissue and effect of N-glycosylation site mutations on biological behaviors of epithelial ovarian cancer cells[J].Journal of Jilin University(Medicine Edition), 2026, 52(2): 469-482.

Figures/Tables 15

Fig. 1

Tab.1

Fig. 2

Tab.2

Fig. 3

Tab.3

Fig. 4

Fig. 5

Tab.4

Fig. 6

Fig. 7

Fig. 8

Fig. 9

Tab.5

Fig. 10

References 22

[1]	LOKMAN N A， RICCIARDELLI C， STEPHENS A N， et al. Diagnostic value of plasma annexin A2 in early-stage high-grade serous ovarian cancer［J］. Diagnostics， 2021， 11（1）： 69.
[2]	ZHANG R Q， SIU M K Y， NGAN H Y S， et al. Molecular biomarkers for the early detection of ovarian cancer［J］. Int J Mol Sci， 2022， 23（19）： 12041.
[3]	FERNÁNDEZ L P， SÁNCHEZ-MARTÍNEZ R， VARGAS T， et al. The role of glycosyltransferase enzyme GCNT3 in colon and ovarian cancer prognosis and chemoresistance［J］. Sci Rep， 2018， 8（1）： 8485.
[4]	AN H J， FROEHLICH J W， LEBRILLA C B. Determination of glycosylation sites and site-specific heterogeneity in glycoproteins［J］. Curr Opin Chem Biol， 2009， 13（4）： 421-426.
[5]	ZHANG J， DIJKE PTEN， WUHRER M， et al. Role of glycosylation in TGF-β signaling and epithelial-to-mesenchymal transition in cancer［J］. Protein Cell， 2021， 12（2）： 89-106.
[6]	于盼盼，杨萍，孙倩玉，等. 宫颈癌组织GSTO1的表达与宫颈癌预后的相关性分析及其N-糖基化对宫颈癌恶性生物学行为的影响［J］. 安徽医科大学学报， 2023， 58（12）： 2002-2010.
[7]	SIMIC P， CORIC V， PLJESA I， et al. The role of glutathione transferase omega-class variant alleles in individual susceptibility to ovarian cancer［J］. Int J Mol Sci， 2024， 25（9）： 4986.
[8]	GUO J， CAI J， ZHANG Y X， et al. Establishment of two ovarian cancer orthotopic xenograft mouse models for in vivo imaging： a comparative study［J］. Int J Oncol， 2017， 51（4）： 1199-1208.
[9]	孙崇凤，杨萍，侯纪帅，等. STT3A和STT3B在上皮性卵巢癌中的表达及与预后的关系［J］. 实用医学杂志， 2023， 39（16）： 2062-2070.
[10]	YANG C， XIA B R， ZHANG Z C， et al. Immunotherapy for ovarian cancer： adjuvant， combination， and neoadjuvant［J］. Front Immunol， 2020， 11： 577869.
[11]	XU Y B， BANKHEAD A 3rd， TIAN X L， et al. Deletion of glutathione S-transferase omega 1 activates type Ⅰ interferon genes and downregulates tissue factor［J］. Cancer Res， 2020， 80（17）： 3692-3705.
[12]	PETROVIC M， SIMIC T， DJUKIC T， et al. The polymorphisms in GSTO genes （GSTO1 rs4925， GSTO2 rs156697， and GSTO2 rs2297235） affect the risk for testicular germ cell tumor development： a pilot study［J］. Life， 2023， 13（6）： 1269.
[13]	WANG L K， YUE H L， PENG X J， et al. GSTO1 regards as a meritorious regulator in cutaneous malignant melanoma cells［J］. Mol Cell Probes， 2019， 48： 101449.
[14]	MA H， CHEN X L， MO S W， et al. Targeting N-glycosylation of 4F2hc mediated by glycosyltransferase B3GNT3 sensitizes ferroptosis of pancreatic ductal adenocarcinoma［J］. Cell Death Differ， 2023， 30（8）： 1988-2004.
[15]	HE L N， GUO Z J， WANG W J， et al. FUT2 inhibits the EMT and metastasis of colorectal cancer by increasing LRP1 fucosylation［J］. Cell Commun Signal， 2023， 21（1）： 63.
[16]	井玉莹，杨凯歌，程仪婷，等. EZH2通过EMT促进食管鳞状细胞癌的恶性生物学行为［J］. 中南大学学报（医学版）， 2025， 50（2）： 155-166.
[17]	PARK M， KIM D， KO S， et al. Breast cancer metastasis： mechanisms and therapeutic implications［J］. Int J Mol Sci， 2022， 23（12）： 6806.
[18]	BABAEI G， AZIZ S G， JAGHI N Z Z. EMT， cancer stem cells and autophagy； The three main axes of metastasis［J］. Biomed Pharmacother， 2021， 133： 110909.
[19]	张哲，罗怡欣，陈卓，等. 中性粒细胞源性外泌体在乳腺癌细胞侵袭、转移中的作用［J］. 郑州大学学报（医学版）， 2025， 60（4）： 484-487.
[20]	王姜婷，孙恺，高谋，等. SIRT7调控上皮-间质转化对胶质瘤细胞增殖和迁移的作用［J］. 解放军医学杂志， 2025， 50（1）： 57-68.
[21]	李瑛花，杨娟. LncRNA RP11-499E18.1对卵巢癌细胞恶性生物学行为的影响［J］. 中南大学学报（医学版）， 2025， 50（1）： 1-10.
[22]	王发辉，邓青春，林佳佳，等. GATA3介导miR-21/PTEN轴对子宫内膜癌细胞增殖、侵袭的影响［J］. 实用医学杂志， 2024， 40（15）： 2069-2074.

Characteristic		Number
Age（year）
≤52		48 （54.5）
>52		40 （45.5）
FIGO Stage（2014）
Ⅰ		36 （41.0）
Ⅱ		12 （13.6）
Ⅲ		39 （44.3）
Ⅳ		1 （1.1）
Pathological type
Plasmacytoid cancer		65 （73.9）
Mucinous carcinoma		7 （8.0）
Clear cell carcinoma		6 （6.8）
Endometrioid cancer		9 （10.2）
Mixed epithelial carcinoma		1 （1.1）
Grade
Low		17 （19.3）
Middle		9 （10.2）
High		62 （70.5）
LVSI
Yes		24 （27.3）
No		64 （72.7）
LNM
Yes		29 （33.0）
No		59 （67.0）
Size（cm）
≤8		46 （52.3）
>8		42 （47.7）
CA125（U·mL^-1）
≤200		48 （54.5）
>200		40 （45.5）

Characteristic	n	GSTO1		χ²	P
Characteristic	n	Low	High	χ²	P
Age（year）				0.244	0.621
≤52	48	13（27.1）	35（72.9）
>52	40	9（22.5）	31（77.5）
FIGO Stage（2014）				6.111	0.013
Ⅰ-Ⅱ	48	17（35.4）	31（64.6）
Ⅲ-Ⅳ	40	5（12.5）	35（87.5）
Pathological type				0.491	0.484
Plasmacytoid cancer	65	15（23.1）	50（76.9）
Adenocarcinoma	23	7（30.4）	16（69.6）
Grade				0.024	0.876
Low	17	4 （23.5）	13（76.5）
Other divisions	71	18（25.4）	53（74.6）
CA125（U·mL^-1）				0.244	0.621
≤200	48	13（27.1）	35（72.9）
>200	40	9（22.5）	31（77.5）
Size（cm）				26.783	<0.001^*
≤8	46	22（47.8）	24（52.2）
>8	42	0（0.0）	42（100.0）
LVSI				4.889	0.027
Yes	24	10（41.7）	14（58.3）
No	64	12（18.8）	52（81.2）
LNM				0.017	0.896
Yes	29	7（24.1）	22（75.9）
No	59	15（25.4）	44（74.6）

Characteristic	Univariate Cox analysis			Multivariate Cox analysis
Characteristic	HR	95%CI	P	HR	95%CI	P
FIGO stage （Ⅲ-Ⅳ vs Ⅰ-Ⅱ）	9.948	4.037-24.510	0.001	14.272	3.509-58.042	0.001
Grade （High vs low）	1.719	0.600-4.928	0.919
Size （>8 cm vs ≤8 cm）	4.698	2.030-10.873	0.001	0.516	0.113-2.345	0.392
LVSI （Positive vs negative）	1.999	0.974-4.103	0.059
LNM （Positive vs negative）	3.271	1.582-6.764	0.001	3.397	1.606-7.183	0.001
GSTO1 （High vs low）	3.376	1.138-10.017	0.028	4.881	1.024-23.270	0.029

Characteristics	Univariate Cox analysis			Multivariate Cox analysis
Characteristics	HR	95%CI	P	HR	95%CI	P
FIGO stage （Ⅲ-Ⅳ vs Ⅰ-Ⅱ）	8.109	3.765-17.462	0.001	8.468	2.765-25.933	0.001
Grade （High vs low）	1.427	0.597-3.408	0.424
Size （>8 cm vs ≤8 cm）	4.864	2.349-10.069	0.001	0.669	0.193-2.320	0.526
LVSI （Positive vs negative）	1.483	0.776-2.834	0.233
LNM （Positive vs negative）	2.306	1.220-4.358	0.010	2.583	1.335-14.588	0.005
GSTO1 （High vs low）	4.782	1.695-13.488	0.003	4.119	1.163-14.588	0.028

Expression of GSTO1 in ovarian cancer tissue and effect of N-glycosylation site mutations on biological behaviors of epithelial ovarian cancer cells

RichHTML

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 15

References 22

Related Articles 15

Metrics

Comments

Recommended 0

[1]	Yao ZHENG,Mingxia FU,Weichen WANG,Weiwei CHEN,Yuchen HAN,Yu BAI,Jiajia AN. Effect of sodium selenite on biological behaviors of breast cancer doxorubicin-resistant MCF-7/ADR cells [J]. Journal of Jilin University(Medicine Edition), 2026, 52(2): 410-417.
[2]	Li ZHAI,Meng CHEN,Jianbo LUO,Aili ZHANG,Liangxiao WANG,Ying WEI,Xi ZHANG. Targeting relationship between miR-214-3p and EZH2 and its effects on proliferation， invasion， and apoptosis of ovarian cancer SKOV3 cells [J]. Journal of Jilin University(Medicine Edition), 2026, 52(2): 460-468.
[3]	Yunshan DING,Haitao DAI,Min CHEN,Xiaohui HAO,Xiao ZHOU,Nan WU. Effect of silencing TRPV2 gene and cannabidiol on biological behaviors of oral squamous cell carcinoma CAL-27 cells [J]. Journal of Jilin University(Medicine Edition), 2026, 52(1): 143-151.
[4]	Yan ZHAO,Huawei WU. Inhibitory effect of inhibition of miR-17-5p on proliferation of spinal cord astrocytes of rats induced by scratch injury through targeting Mfn2 expression [J]. Journal of Jilin University(Medicine Edition), 2026, 52(1): 81-92.
[5]	Xiaohan YAO,Mingchen YAO,Zhiqing WANG,Heyang LI,Yan YAN,Ningjing LEI. Effect of silencing GPR139 gene on proliferation, apoptosis and autophagy of breast cancer cells and its mechanism [J]. Journal of Jilin University(Medicine Edition), 2026, 52(1): 1-9.
[6]	Sifan FENG,Yunfeng LI,Jiaying WANG,Fubin MA,Yan WANG. Effects of heme-binding protein 1 gene knockdown on proliferation, migration, and inflammatory response of microglia BV2 and their mechanisms [J]. Journal of Jilin University(Medicine Edition), 2025, 51(6): 1532-1541.
[7]	Lulu FU,Yinggang ZOU,Xiaoyu ZHENG,Xueying ZHANG,Jingshun ZHANG,Min WANG,Qiang ZHANG,Lianwen ZHENG. Expression of placenta expressed transcription factor 1 in ovarian tissue of polycystic ovary syndrome rats and its effect on proliferation of rat ovarian granulosa cells [J]. Journal of Jilin University(Medicine Edition), 2025, 51(5): 1177-1184.
[8]	Pingsheng ZHU,Sitang GE,Lugen ZUO,Deli CHEN,Yangyang ZHANG. Effect of miR-325-3p targeting PRELID1 gene in regulation of EMT pathway on invasion and migration of colon cancer cells and their mechanisms [J]. Journal of Jilin University(Medicine Edition), 2025, 51(5): 1185-1193.
[9]	Wenxuan LI,Minru ZONG. Research progress in role of migration of Schwann cells in repairment of peripheral nerve injury [J]. Journal of Jilin University(Medicine Edition), 2025, 51(4): 1137-1144.
[10]	Zhongjun SHEN,Yao ZHAO,Mingbo JIA,Liyan ZHAO. Research progress in effects of hypoxia-inducible factors on cell migration and invasion during epithelial-mesenchymal transition in glioma cells [J]. Journal of Jilin University(Medicine Edition), 2025, 51(4): 1145-1154.
[11]	Yixuan GAO,Peng WANG,Silong ZHANG,Ruijuan GAO,Yingfang MA,Keke ZHANG,Dan FENG,Zongqi HUANG,Ketao MA,Li LI,Junqiang SI. Inhibitory effect of safranal on proliferation, migration and phenotypic transformation of vascular smooth muscle cells of rats induced by high glucose in vitro [J]. Journal of Jilin University(Medicine Edition), 2025, 51(4): 948-957.
[12]	Xiaoshuang HE,Lina XU,Mei CUI,Yu ZHAO,Bei WANG,Zheng HUANG,Yuchao WANG,Wenyan XIN,Chao WU. Effects of lncRNA DUXAP8 in lung cancer A549 cells-derived exosomes on lung cancer cell growth and its mechnism [J]. Journal of Jilin University(Medicine Edition), 2025, 51(4): 958-967.
[13]	Hongli LI,Mengyao WANG,Yangyang LIU,Hui ZHANG,Li LI. Effect of KHSRP on biological behavior of colorectal cancer cells through activation of JAK/STAT signaling pathway [J]. Journal of Jilin University(Medicine Edition), 2025, 51(4): 996-1006.
[14]	Xingxiang WANG,Ying ZHAO,Qiaotong REN,Hefei WANG,Gang PU,Chun LI. Promotive effect of M2 macrophages on epithelial-mesenchymal transition and cisplatin resistance in non-small cell lung cancer A549 cells by regulating NF-κB signaling pathway [J]. Journal of Jilin University(Medicine Edition), 2025, 51(3): 642-652.
[15]	Donghui LIU,Yunzhe CI,Chunyan WANG,Wenyi MA. Effect of miR-199a-5p on expression of Caveolin-1, cell migration and apoptosis in glioma U251 cells [J]. Journal of Jilin University(Medicine Edition), 2025, 51(3): 663-671.