GINS2 is a novel prognostic biomarker and promotes tumor progression in early-stage cervical cancer

被引：73

作者：

Fei Ouyang ^{[1
]}

Liu, Junling ^{[2
]}

Xia, Meng ^{[1
]}

Lin, Chuyong ^{[3
]}

Wu, Xianqiu ^{[3
]}

Ye, Liping ^{[3
]}

Song, Libing ^{[3
]}

Li, Jun ^{[4
]}

Wang, Jing ^{[1
]}

Guo, Peng ^{[1
]}

He, Mian ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Gynecol & Obstet, 58 Zhongshan Second Rd, Guangzhou 510080, Guangdong, Peoples R China

[2] Sun Yat Sen Univ, Canc Ctr, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol Southern China,Dept Med Oncol, Guangzhou, Guangdong, Peoples R China

[3] Sun Yat Sen Univ, Canc Ctr, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol Southern China,Dept Expt Res, Guangzhou, Guangdong, Peoples R China

[4] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Biochem, Guangzhou, Guangdong, Peoples R China

来源：

ONCOLOGY REPORTS | 2017年 / 37卷 / 05期

基金：

中国国家自然科学基金;

关键词：

GINS2; cervical cancer; prognosis; proliferation; tumorigenesis; migration; invasion; SQUAMOUS-CELL CARCINOMA; CLINICAL-PRACTICE GUIDELINES; S-PHASE CHECKPOINT; HUMAN-PAPILLOMAVIRUS; SCC ANTIGEN; DNA-REPLICATION; CYFRA; 21-1; SERUM; EXPRESSION; COMPLEX;

D O I：

10.3892/or.2017.5573

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

GINS complex subunit 2 (GINS2), a member of the GINS complex, is involved in DNA replication. GINS2 is upregulated in a variety of aggressive tumors. However, its role in cervical cancer carcinogenesis remains to be elucidated. We investigated the clinical significance of GINS2 in patients with early-stage cervical cancer and its biological functions in cervical cancer progression. GINS2 expression was analyzed in cervical cancer cell lines and in 8 matched cervical cancer samples at the mRNA and protein levels using real-time PCR and western blotting, respectively. GINS2 protein expression in 155 paraffin-embedded cervical cancer specimens was validated using immunohistochemistry. Statistical analysis was used to evaluate its clinicopathological significance. Short hairpin RNA interference, anchorage-independent growth ability, colony formation assay, wound healing ability, Transwell assays and western blotting were used to determine the effects of GINS2 on the aggressive phenotype of cervical cancer cells. There was obvious upregulation of GINS2 in the cervical cancer cell lines and tumor specimens compared to that in the normal cervical tissues. Significant correlations were identified between GINS2 expression and squamous cell carcinoma antigen (SCC-Ag; P<0.001), deep stromal invasion (P=0.021), vital status (P<0.001), recurrence (P<0.001) and pelvic lymph node metastasis (PLNM; P<0.001). Moreover, patients with higher GINS2 expression had shorter overall survival (OS) compared to patients with low GINS2 expression. Multivariate analysis revealed that GINS2 may serve as an independent risk factor of poor prognosis in early-stage cervical cancer. In addition, GINS2 downregulation markedly suppressed cell proliferation and tumorigenic ability, as well as cell migration and invasion. Our findings suggest that GINS2 is a novel indicator of PLNM and a valuable prognostic biomarker in early-stage cervical cancer, and subsequently is a valuable molecular target for cervical cancer diagnosis and treatment.

引用

页码：2652 / 2662

页数：11

共 42 条

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