title: GINS2 is a novel prognostic biomarker and promotes tumor progression in early-stage cervical cancer.
abstract: 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.
authors.affiliation: Department of Gynecology and Obstetrics, The First Afﬁliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Ouyang
authors.affiliation: State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.
authors.forename: Junling
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Gynecology and Obstetrics, The First Afﬁliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.
authors.forename: Chuyong
authors.initials: C
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.
authors.forename: Xianqiu
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.
authors.forename: Liping
authors.initials: L
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.
authors.forename: Libing
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Gynecology and Obstetrics, The First Afﬁliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gynecology and Obstetrics, The First Afﬁliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Guo
authors.affiliation: Department of Gynecology and Obstetrics, The First Afﬁliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Mian
authors.initials: M
authors.lastname: He
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; C556406:GINS2 protein, human