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      High Expression of KIF20A Is Associated with Poor Overall Survival and Tumor Progression in Early-Stage Cervical Squamous Cell Carcinoma

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          Abstract

          Background

          The kinesin family member 20a (KIF20A) protein has been implicated in the development and progression of many human cancers; however, its precise function and role in cervical cancer remain largely unclear. This study aimed to investigate the expression profile and prognostic value of KIF20A in patients with early-stage cervical squamous cell carcinoma.

          Methods

          We examined the mRNA and protein levels of KIF20A in eight cervical cancer cell lines and eight paired cervical cancer samples, compared with normal cervical epithelial cells and adjacent normal cervical tissues, respectively. Immunohistochemistry was performed to detect the expression of KIF20A in paraffin-embedded specimens from 169 early-stage cervical squamous cell carcinoma patients. Statistical analyses were applied to analyze the association between KIF20A expression and clinical variables, as well with patient survival.

          Results

          The mRNA and protein expression levels of KIF20A were significantly elevated in cervical cancer cell lines and lesions compared with normal cells and corresponding normal tissues ( P < 0.05). Immunohistochemistry analysis in 169 cervical cancer cases revealed that increased KIF20A expression was strongly associated with human papillomavirus (HPV) infection ( P = 0.008), clinical stage ( P = 0.001), tumor recurrence ( P = 0.016), vital status ( P < 0.001), the property of the surgical margin ( P = 0.032), the lymphovascular space involvement ( P = 0.014), and pelvic lymph node metastasis ( P = 0.001). The overall survival and disease-free survival of patients with high levels of KIF20A expression were significantly poorer than those with low KIF20A expression. KIF20A was an independent survival prognostic factor, as evidenced by univariate and multivariate analysis.

          Conclusions

          Our results illustrate that elevated KIF20A expression correlates with HPV infection, clinical stage, tumor recurrence, lymphovascular space involvement, pelvic lymph node metastasis, and poor outcome in early-stage cervical squamous cell carcinoma patients. KIF20A aberrant expression is a novel independent unfavorable prognostic factor and may present a potential therapeutic target for cervical cancer.

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          Most cited references38

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          Interaction of a Golgi-associated kinesin-like protein with Rab6.

          Rab guanosine triphosphatases regulate vesicular transport and membrane traffic within eukaryotic cells. Here, a kinesin-like protein that interacts with guanosine triphosphate (GTP)-bound forms of Rab6 was identified. This protein, termed Rabkinesin-6, was localized to the Golgi apparatus and shown to play a role in the dynamics of this organelle. The carboxyl-terminal domain of Rabkinesin-6, which contains the Rab6-interacting domain, inhibited the effects of Rab6-GTP on intracellular transport. Thus, a molecular motor is a potential effector of a Rab protein, and coordinated action between members of these two families of proteins could control membrane dynamics and directional vesicular traffic.
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            Loss of the forkhead transcription factor FoxM1 causes centrosome amplification and mitotic catastrophe.

            Expression of the forkhead transcription factor FoxM1 correlates with proliferative status in a variety of normal and transformed cell types. Elevated expression of FoxM1 has been noted in both hepatocellular carcinoma and basal cell carcinoma. However, whether FoxM1 expression is essential for the viability of transformed cells is unknown. We report here that the expression of FoxM1 is significantly elevated in primary breast cancer. Microarray analysis shows that FoxM1 regulates genes that are essential for faithful chromosome segregation and mitosis, including Nek2, KIF20A, and CENP-A. Loss of FoxM1 expression generates mitotic spindle defects, delays cells in mitosis, and induces mitotic catastrophe. Time-lapse microscopy indicates that depletion of FoxM1 generates cells that enter mitosis but are unable to complete cell division, resulting in either mitotic catastrophe or endoreduplication. These findings indicate that FoxM1 depletion causes cell death due to mitotic catastrophe and that inhibiting FoxM1 represents a therapeutic strategy to target breast cancer.
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              Radioimmunoassay for tumor antigen of human cervical squamous cell carcinoma.

              A heterologous antiserum for human cervical squamous cell carcinoma was prepared and specificity determined by Ouchterlony immunodiffusion and immunofluorescence studies. With this antiserum, a tumor antigen was purified from human cervical squamous cell carcinoma tissue. The specificities of the antigen and the antiserum were then re-examined by a radioimmunoassay method using 125 I-labeled purified antigen. Although normal cervical tissue extract showed a moderate cross-reactivity in the radioimmunoassay, the circulating antigen activity could not be detected in normal women or in several patients with carcinomas, whereas 27 of 35 patients with cervical squamous cell carcinoma showed detectable serum antigen activity. All aptients with advanced stages of cervical squamous cell carcinoma showed detectable antigen levels. These results indicate that there is a quantitative abnormality, at least, of this tumor antigen in patients with cervical squamous cell carcinoma and that the radioimmunoassay for the antigen is a potentially useful tool in clinical care.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                12 December 2016
                2016
                : 11
                : 12
                : e0167449
                Affiliations
                [1 ]Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
                [2 ]Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-Sen University, GuangZhou, People’s Republic of China
                [3 ]Department of Clinical Examination, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China
                [4 ]Eight-year program, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, People’s Republic of China
                University of North Carolina at Chapel Hill School of Medicine, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: CX YZ WZ.

                • Data curation: YS WH.

                • Formal analysis: NZ ZL.

                • Funding acquisition: YZ CX.

                • Investigation: YS WH.

                • Methodology: WH HG.

                • Project administration: YZ WZ.

                • Resources: YZ CX.

                • Software: YS.

                • Supervision: YZ.

                • Validation: ML YF.

                • Visualization: WZ.

                • Writing – original draft: WZ WH.

                • Writing – review & editing: YZ CX.

                Article
                PONE-D-16-32186
                10.1371/journal.pone.0167449
                5152822
                27941992
                8a8d2fae-68ef-42a2-acbd-228f52673410
                © 2016 Zhang et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 11 August 2016
                : 14 November 2016
                Page count
                Figures: 5, Tables: 4, Pages: 21
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Gynecological Tumors
                Cervical Cancer
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Carcinomas
                Squamous Cell Carcinomas
                Medicine and Health Sciences
                Urology
                Genitourinary Infections
                Human Papillomavirus Infection
                Medicine and Health Sciences
                Infectious Diseases
                Sexually Transmitted Diseases
                Human Papillomavirus Infection
                Medicine and Health Sciences
                Infectious Diseases
                Viral Diseases
                Human Papillomavirus Infection
                Biology and Life Sciences
                Molecular Biology
                Molecular Biology Techniques
                Molecular Biology Assays and Analysis Techniques
                Gene Expression and Vector Techniques
                Protein Expression
                Research and Analysis Methods
                Molecular Biology Techniques
                Molecular Biology Assays and Analysis Techniques
                Gene Expression and Vector Techniques
                Protein Expression
                Medicine and Health Sciences
                Oncology
                Cancer Treatment
                Chemotherapy
                Medicine and Health Sciences
                Clinical Medicine
                Clinical Oncology
                Chemotherapy
                Medicine and Health Sciences
                Oncology
                Clinical Oncology
                Chemotherapy
                Medicine and Health Sciences
                Pharmaceutics
                Drug Therapy
                Chemotherapy
                Medicine and Health Sciences
                Oncology
                Cancer Treatment
                Radiation Therapy
                Medicine and Health Sciences
                Clinical Medicine
                Clinical Oncology
                Radiation Therapy
                Medicine and Health Sciences
                Oncology
                Clinical Oncology
                Radiation Therapy
                Medicine and Health Sciences
                Oncology
                Cancer Treatment
                Surgical Oncology
                Medicine and Health Sciences
                Clinical Medicine
                Clinical Oncology
                Surgical Oncology
                Medicine and Health Sciences
                Oncology
                Clinical Oncology
                Surgical Oncology
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
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