GINS2 is a novel prognostic biomarker and promotes tumor progression in early-stage cervical cancer
Authors: Meng Xia
Xianqiu Wu
Mian He
Chuyong Lin
Peng Guo
Jun Li
Jing Wang
Fei Ouyang
Junling Liu
Libing Song
Liping Ye
Journal: Oncology Reports (2017)
Discipline: CLINICAL MEDICINE
Keywords: GINS2; cervical cancer; prognosis; biomarker; DNA replication
Affiliations: Department of Gynecology and Obstetrics, The First Afﬁliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China., 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., 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., Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, P.R. China.

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&lt;0.001), deep stromal invasion (P=0.021), vital status (P&lt;0.001), recurrence (P&lt;0.001) and pelvic lymph node metastasis (PLNM; P&lt;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. 

Retracted: No

PubPeer comments:
 Figure 2C appears to have a repeated image. *** ![file] , 
 Figure 6C appears to have two images which overlap. *** ![file] , 
 Corrigendum [16 March 2021] . ------------------------- Subsequently to the publication of the above article, the authors have realized that Figs. 2 and 6 each contained an incorrectly assembled data panel: Essentially, a couple of the data panels had been inadvertently selected twice for these figures. The corrected versions of Figs 2 and 6, including the correct data for the H E staining of the tissue of patient 4 in Fig. 2C and the invaded cells of RNAi#2 of the Siha cell line in Fig. 6C, are shown below and on the next page. All the authors agree to the publication of this Corrigendum, and they thank the Editor of Oncology Reports for allowing them the opportunity to publish it. Furthermore, they apologize to the readership for any inconvenience caused. ![] Figure 2. - Western blotting, qPCR, and IHC determination of GINS2 mRNA and protein expression. (A) Western blotting and qPCR of GINS2 expression in normal cervical tissues and cervical cancer cell lines. (B) Western blotting of GINS2 expression in 8 pairs of matched cervical cancer (T) and adjacent non-cancerous cervical tissues (ANT) and average T ANT ratios of GINS2 mRNA expression quantified by qPCR in 8 pairs of matched cervical cancer tissues. Expression levels were normalized to u03b1-tubulin expression. Error bars represent standard deviation (SD) calculated from 3 parallel experiments. *P 0.05. (C) IHC assay of GINS2 protein expression in 8 pairs of matched cervical cancer tissues. ![] Figure 6. - GINS2 is essential for cervical cancer cell migration and invasion. (A) Cell mobility was measured by examining the rate of wound closure at 0, 24 and 48 h. Original magnification, u00d7200. (B) Transwell migration assay investigation of the mobility properties induced by fetal bovine serum. Original magnification, u00d7200; *P 0.05. (C) Transwell invasion assay of the invasive properties induced by fetal bovine serum. Original magnification, u00d7200; *P 0.05. Bars represent the mean u00b1 SD of 3 independent experiments , 
 Figure 6A of the correction (above) appears to have 2 images which overlap. This may be a systemic issue for papers with one or more common authors: https: pubpeer.com search?q=authors%3A Libing+Song *** ![file] , 
 Dear Actinopolyspora Biskrensis Thanks for pointing this out. We are currently checking the original data of these figures, and will make response as soon as possible. Mian He ,