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      GOLPH3L is a Novel Prognostic Biomarker for Epithelial Ovarian Cancer

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          Abstract

          Objective: Golgi phosphoprotein 3 (GOLPH3) is a highly conserved membrane protein that is involved in a variety of cancers such as colorectal cancer, gastric cancer, ovarian cancer, and breast cancer. GOLPH3L is a paralog of GOLPH3. Although these proteins share a similar amino acid sequence, much less is known regarding the subcellular functions or effects of GOLPH3L on cancer compared with GOLPH3. The role of GOLPH3L in epithelial ovarian cancer (EOC) has not yet been investigated.

          Methods: Using western blot, PCR and immunohistochemical analyses, we studied the clinical significance of GOLPH3L expression in EOC. The correlations between GOLPH3L expression and the clinicopathological variables of patients with EOC were assessed using Pearson's χ2 test. Kaplan-Meier analysis was used to compare the postoperative survival between groups of patients with EOC with varying levels of GOLPH3L expression.

          Results: High expression of GOLPH3L was more frequently observed in EOC tissues than in corresponding adjacent non-tumor tissues. The expression of GOLPH3L correlated closely with pre-operative CA125 level (P=0.031). Univariate analysis showed that age, FIGO stage, pre-operative cancer antigen (CA) 125, pre-operative albumin concentration (AC), optimal cytoreductive surgery (CRS) and GOLPH3L expression correlate significantly with overall survival (OS). Multivariate analysis revealed that GOLPH3L expression was an independent prognostic factor for OS of patients with EOC (102 months versus 72 months; P=0.013). What's more, knocked down of GOLPH3L with small interfering RNA (siRNA) technology of OVCAR3 and SKOV3 cell lines reduced cell viability obviously, compared to the negative control and blank control groups.

          Conclusions: Our data show that increased expression of GOLPH3L is associated with poor prognosis of patients with EOC and may act as a novel, useful and independent prognostic indicator. Therefore, further studies are warranted.

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          Recent progress in the diagnosis and treatment of ovarian cancer.

          Danijela Jelovac, Deborah Armstrong (2011)
          Epithelial ovarian cancer is the most lethal of the gynecologic malignancies, largely due to the advanced stage at diagnosis in most patients. Screening strategies using ultrasound and the cancer antigen (CA) 125 tumor marker are currently under study and may lower stage at diagnosis but have not yet been shown to improve survival. Women who have inherited a deleterious mutation in the BRCA1 or BRCA2 gene and those with the Lynch syndrome (hereditary nonpolyposis colorectal cancer) have the highest risk of developing ovarian cancer but account for only approximately 10% of those with the disease. Other less common and less well-defined genetic syndromes may increase the risk of ovarian cancer, but their contribution to genetic risk is small. A clear etiology for sporadic ovarian cancer has not been identified, but risk is affected by reproductive and hormonal factors. Surgery has a unique role in ovarian cancer, as it is used not only for diagnosis and staging but also therapeutically, even in patients with widely disseminated, advanced disease. Ovarian cancer is highly sensitive to chemotherapy drugs, particularly the platinum agents, and most patients will attain a remission with initial treatment. Recent advances in the delivery of chemotherapy using the intraperitoneal route have further improved survival after initial therapy. Although the majority of ovarian cancer patients will respond to initial chemotherapy, most will ultimately develop disease recurrence. Chemotherapy for recurrent disease includes platinum-based, multiagent regimens for women whose disease recurs more than 6 to 12 months after the completion of initial therapy and sequential single agents for those whose disease recurs earlier. New targeted biologic agents, particularly those involved with the vascular endothelial growth factor pathway and those targeting the poly (ADP-ribose) polymerase (PARP) enzyme, hold great promise for improving the outcome of ovarian cancer.
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            Cancer statistics for Hispanics/Latinos, 2012.

            Rebecca Siegel, Deepa Naishadham, Ahmedin Jemal (2012)
            Hispanics/Latinos are the largest and fastest growing major demographic group in the United States, accounting for 16.3% (50.5 million/310 million) of the US population in 2010. In this article, the American Cancer Society updates a previous report on cancer statistics for Hispanics using incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. In 2012, an estimated 112,800 new cases of cancer will be diagnosed and 33,200 cancer deaths will occur among Hispanics. In 2009, the most recent year for which actual data are available, cancer surpassed heart disease as the leading cause of death among Hispanics. Among US Hispanics during the past 10 years of available data (2000-2009), cancer incidence rates declined by 1.7% per year among men and 0.3% per year among women, while cancer death rates declined by 2.3% per year in men and 1.4% per year in women. Hispanics have lower incidence and death rates than non-Hispanic whites for all cancers combined and for the 4 most common cancers (breast, prostate, lung and bronchus, and colorectum). However, Hispanics have higher incidence and mortality rates for cancers of the stomach, liver, uterine cervix, and gallbladder, reflecting greater exposure to cancer-causing infectious agents, lower rates of screening for cervical cancer, differences in lifestyle and dietary patterns, and possibly genetic factors. Strategies for reducing cancer risk among Hispanics include increasing utilization of screening and available vaccines, as well as implementing effective interventions to reduce obesity, alcohol consumption, and tobacco use. Copyright © 2012 American Cancer Society, Inc.
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              Proteomics characterization of abundant Golgi membrane proteins.

              Alexandra P Lewis, Jeffrey A. Bell, J. Paiement … (2001)
              A mass spectrometric analysis of proteins partitioning into Triton X-114 from purified hepatic Golgi apparatus (84% purity by morphometry, 122-fold enrichment over the homogenate for the Golgi marker galactosyl transferase) led to the unambiguous identification of 81 proteins including a novel Golgi-associated protein of 34 kDa (GPP34). The membrane protein complement was resolved by SDS-polyacrylamide gel electrophoresis and subjected to a hierarchical approach using delayed extraction matrix-assisted laser desorption ionization mass spectrometry characterization by peptide mass fingerprinting, tandem mass spectrometry to generate sequence tags, and Edman sequencing of proteins. Major membrane proteins corresponded to known Golgi residents, a Golgi lectin, anterograde cargo, and an abundance of trafficking proteins including KDEL receptors, p24 family members, SNAREs, Rabs, a single ARF-guanine nucleotide exchange factor, and two SCAMPs. Analytical fractionation and gold immunolabeling of proteins in the purified Golgi fraction were used to assess the intra-Golgi and total cellular distribution of GPP34, two SNAREs, SCAMPs, and the trafficking proteins GBF1, BAP31, and alpha(2)P24 identified by the proteomics approach as well as the endoplasmic reticulum contaminant calnexin. Although GPP34 has never previously been identified as a protein, the localization of GPP34 to the Golgi complex, the conservation of GPP34 from yeast to humans, and the cytosolically exposed location of GPP34 predict a role for a novel coat protein in Golgi trafficking.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Cancer
                Journal ID (iso-abbrev): J Cancer
                Journal ID (publisher-id): jca
                Title: Journal of Cancer
                Publisher: Ivyspring International Publisher (Sydney )
                ISSN (Electronic): 1837-9664
                Publication date Collection: 2015
                Publication date (Electronic): 27 July 2015
                Volume: 6
                Issue: 9
                Pages: 893-900
                Affiliations
                1. Department of Gynecologic Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510080, China.
                2. Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA
                3. Department of Biology, University of Illinois at Chicago, Chicago, IL 60607, USA
                4. Department of Forensic Medicine, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China
                Author notes
                ✉ Corresponding author: Jihong Liu, Department of Gynecologic Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, P.R. China. Email: liujh@ 123456sysucc.org.cn ; Tel: +86- 20-87343105.

                # These authors contributed equally to this work and share first authorship.

                Conflicts of interest: The authors declare that no conflicts of interest exist.

                Article
                Publisher ID: jcav06p0893
                DOI: 10.7150/jca.11865
                PMC ID: 4532987
                PubMed ID: 26284141
                SO-VID: 3ca2ed41-b4b2-48ab-8e0c-fc6da124c528
                Copyright © © 2015 Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
                History
                Date received : 11 February 2015
                Date accepted : 11 June 2015
                Categories
                Subject: Research Paper

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: golph3l,epithelial ovarian cancer,prognosis
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: golph3l, epithelial ovarian cancer, prognosis

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