机构:[1]Department of Gynecology and Obstetrics, The First Affliated Hospital of Sun Yat-sen University妇产科妇产科中山大学附属第一医院[2]State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Sun Yat-sen University Cancer Center临床科室其他部门内科华南肿瘤学国家重点实验室中山大学肿瘤防治中心[3]State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center临床科室其他部门临床研究部/药物临床试验机构华南肿瘤学国家重点实验室中山大学肿瘤防治中心[4]Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, P.R. China
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.
基金:
Natural Science Foundation of Guangdong Province [S2013010015552]; National Natural Science Foundation of China [81602723, 81302550, 81671805]; Postdoctoral Science Foundation of China [2016A020215214]; Guangdong Medical Research Foundation [A2015130]
语种:
外文
被引次数:
WOS:
PubmedID:
中科院(CAS)分区:
出版当年[2017]版:
大类|3 区医学
小类|4 区肿瘤学
最新[2023]版:
大类|3 区医学
小类|4 区肿瘤学
第一作者:
第一作者机构:[1]Department of Gynecology and Obstetrics, The First Affliated Hospital of Sun Yat-sen University
共同第一作者:
通讯作者:
通讯机构:[1]Department of Gynecology and Obstetrics, The First Affliated Hospital of Sun Yat-sen University[*1]Department of Gynecology and Obstetrics, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Second Road, Guangzhou 510080, P.R. China
推荐引用方式(GB/T 7714):
Fei Ouyang,Junling Liu,Meng Xia,et al.GINS2 is a novel prognostic biomarker and promotes tumor progression in early-stage cervical cancer[J].ONCOLOGY REPORTS.2017,37(5):2652-2662.doi:10.3892/or.2017.5573.
APA:
Fei Ouyang,Junling Liu,Meng Xia,Chuyong Lin,Xianqiu Wu...&Mian He.(2017).GINS2 is a novel prognostic biomarker and promotes tumor progression in early-stage cervical cancer.ONCOLOGY REPORTS,37,(5)
MLA:
Fei Ouyang,et al."GINS2 is a novel prognostic biomarker and promotes tumor progression in early-stage cervical cancer".ONCOLOGY REPORTS 37..5(2017):2652-2662