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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      MRPL13 is a Prognostic Cancer Biomarker and Correlates with Immune Infiltrates in Breast Cancer

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          Abstract

          Objective

          To study the expression of MRPL13 in breast cancer tissues using TCGA database, analyze the correlation between the expression and clinicopathological characteristics of patients, and explore the role of MRPL13 in the development of breast cancer (BC).

          Methods

          The BC mRNA data and clinical information were downloaded from TCGA database. The correlation between MRPL13 expression and clinicopathological parameters was analyzed. Cox regression multivariate analysis was used to explore the factors affecting the prognosis of BC patients. The UALCAN database was used to analyze the expression level of MRPL13 in BC and its relationship with clinical pathological factors. The GSEA method was used to predict the possible regulatory pathways of MRPL13. Immune responses of MRPL13 expression were analyzed using TISIDB and CIBERSORT. Additionally, GEPIA, K-M survival analysis and data from the HPA were used to validate the outcomes.

          Results

          The expression of MRPL13 in BC tissues was significantly higher than normal counterparts, patients with low MRPL13 expression had a better survival prognosis, also indicated an independent prognostic factor. GSEA analysis showed that the regulation of cell migration, positive regulation of endothelial cell migration, and Notch signaling pathway were enriched in tissues with low expression of MRPL13. Additionally, depleting MRPL13 expression inhibited invasion in MCF-10A and MCF-7 cells. Furthermore, PCR showed that MRPL13 affected VEGFA and MMP gene expression. CIBERSORT analysis revealed that the amount of NK cells decreased when MRPL13 expression was high.

          Conclusion

          The expression of MRPL13 mRNA is upregulated in BC tissues, and the expression level of MRPL13 is significantly related to the clinicopathological factors of patients. High MRPL13 expression is a poor prognostic factor for BC, and it can be used as a molecular marker for prognosis judgment and as a potential therapeutic target.

          Most cited references51

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          Roles of the immune system in cancer: from tumor initiation to metastatic progression

          Hugo González, Catharina Hagerling, Zena Werb (2018)
          In this review, Gonzelez et al. provide an update of recent accomplishments, unifying concepts, and futures challenges to study tumor-associated immune cells, with an emphasis on metastatic carcinomas. The presence of inflammatory immune cells in human tumors raises a fundamental question in oncology: How do cancer cells avoid the destruction by immune attack? In principle, tumor development can be controlled by cytotoxic innate and adaptive immune cells; however, as the tumor develops from neoplastic tissue to clinically detectable tumors, cancer cells evolve different mechanisms that mimic peripheral immune tolerance in order to avoid tumoricidal attack. Here, we provide an update of recent accomplishments, unifying concepts, and future challenges to study tumor-associated immune cells, with an emphasis on metastatic carcinomas.
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            CTLA-4: a moving target in immunotherapy.

            Behzad Rowshanravan, Neil Halliday, David M. Sansom (2018)
            CD28 and CTLA-4 are members of a family of immunoglobulin-related receptors that are responsible for various aspects of T-cell immune regulation. The family includes CD28, CTLA-4, and ICOS as well as other proteins, including PD-1, BTLA, and TIGIT. These receptors have both stimulatory (CD28, ICOS) and inhibitory roles (CTLA-4, PD-1, BTLA, and TIGIT) in T-cell function. Increasingly, these pathways are targeted as part of immune modulatory strategies to treat cancers, referred to generically as immune checkpoint blockade, and conversely to treat autoimmunity and CTLA-4 deficiency. Here, we focus on the biology of the CD28/CTLA-4 pathway as a framework for understanding the impacts of therapeutic manipulation of this pathway.
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              Defining the role of the tumor vasculature in antitumor immunity and immunotherapy

              Marco Schaaf, Abhishek D. Garg, Patrizia Agostinis (2018)
              It is now well established that cancer cells co-exist within a complex environment with stromal cells and depend for their growth and dissemination on tight and plastic interactions with components of the tumor microenvironment (TME). Cancer cells incite the formation of new blood and lymphatic vessels from preexisting vessels to cope with their high nutrient/oxygen demand and favor tumor outgrowth. Research over the past decades has highlighted the crucial role played by tumor-associated blood and lymphatic vasculature in supporting immunoevasion and in subverting T-cell-mediated immunosurveillance, which are the main hallmarks of cancers. The structurally and functionally aberrant tumor vasculature contributes to the protumorigenic and immunosuppressive TME by maintaining a cancer cell’s permissive environment characterized by hypoxia, acidosis, and high interstitial pressure, while simultaneously generating a physical barrier to T cells' infiltration. Recent research moreover has shown that blood endothelial cells forming the tumor vessels can actively suppress the recruitment, adhesion, and activity of T cells. Likewise, during tumorigenesis the lymphatic vasculature undergoes dramatic remodeling that facilitates metastatic spreading of cancer cells and immunosuppression. Beyond carcinogenesis, the erratic tumor vasculature has been recently implicated in mechanisms of therapy resistance, including those limiting the efficacy of clinically approved immunotherapies, such as immune checkpoint blockers and adoptive T-cell transfer. In this review, we discuss emerging evidence highlighting the major role played by tumor-associated blood and lymphatic vasculature in thwarting immunosurveillance mechanisms and antitumor immunity. Moreover, we also discuss novel therapeutic approaches targeting the tumor vasculature and their potential to help overcoming immunotherapy resistance.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Onco Targets Ther
                Journal ID (iso-abbrev): Onco Targets Ther
                Journal ID (publisher-id): ott
                Journal ID (pmc): ott
                Title: OncoTargets and therapy
                Publisher: Dove
                ISSN (Electronic): 1178-6930
                Publication date (Electronic): 27 November 2020
                Publication date Collection: 2020
                Volume: 13
                Pages: 12255-12268
                Affiliations
                [1 ]Department of Breast Surgery, The First Hospital of China Medical University , Shenyang, Liaoning Province 110001, People’s Republic of China
                Author notes
                Correspondence: Zuo Tao; Bo Chen Department of Breast Surgery, The First Hospital of China Medical University , 155 North Nanjing Street, Heping District, Shenyang, Liaoning Province110001, People’s Republic of China Email bochen@cmu.edu.cn; taozuocmu@163.com
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0002-9072-308X
                http://orcid.org/0000-0002-6702-6526
                http://orcid.org/0000-0002-2216-2794
                Article
                Publisher ID: 263998
                DOI: 10.2147/OTT.S263998
                PMC ID: 7708783
                PubMed ID: 33273831
                SO-VID: 014d68c2-caa1-4526-8be8-d1e6947962bc
                Copyright © © 2020 Tao et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 04 July 2020
                Date accepted : 13 October 2020
                Page count
                Figures: 4, Tables: 4, References: 51, Pages: 14
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cancer genome map,breast cancer,mrpl13,clinical significance
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cancer genome map, breast cancer, mrpl13, clinical significance

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