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      Hallmarks of Cancer-Related Newly Prognostic Factors of Oral Squamous Cell Carcinoma

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          Abstract

          Head and neck cancer, including oral squamous cell carcinoma (OSCC), is the sixth leading malignancy worldwide. OSCC is an aggressive tumor and its prognosis has exhibited little improvement in the last three decades. Comprehensive elucidation of OSCC’s molecular mechanism is imperative for early detection and treatment, improving patient survival. Based on broadly accepted notions, OSCC arises from multiple genetic alterations caused by chronic exposure to carcinogens. In 2011, research revealed 10 key alterations fundamental to cancer cell development: sustaining proliferative signaling, evading growth suppressors, avoiding immune destruction, activating invasion and metastasis, tumor-promoting inflammation, enabling replicative immortality, inducing angiogenesis, genome instability and mutation, resisting cell death, and deregulating energetics. This review describes molecular pathological findings on conventional and novel hallmarks of OSCC prognostic factors. In addition, the review summarizes the functions and roles of several molecules as novel OSCC prognosticators.

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          On the origin of cancer cells.

          O WARBURG (1956)
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            miR-126 regulates angiogenic signaling and vascular integrity.

            Jason Fish, Massimo M. Santoro, Sarah Morton … (2008)
            Precise regulation of the formation, maintenance, and remodeling of the vasculature is required for normal development, tissue response to injury, and tumor progression. How specific microRNAs intersect with and modulate angiogenic signaling cascades is unknown. Here, we identified microRNAs that were enriched in endothelial cells derived from mouse embryonic stem (ES) cells and in developing mouse embryos. We found that miR-126 regulated the response of endothelial cells to VEGF. Additionally, knockdown of miR-126 in zebrafish resulted in loss of vascular integrity and hemorrhage during embryonic development. miR-126 functioned in part by directly repressing negative regulators of the VEGF pathway, including the Sprouty-related protein SPRED1 and phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2/p85-beta). Increased expression of Spred1 or inhibition of VEGF signaling in zebrafish resulted in defects similar to miR-126 knockdown. These findings illustrate that a single miRNA can regulate vascular integrity and angiogenesis, providing a new target for modulating vascular formation and function.
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              Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer.

              J Smith, Natasha Deane, Fei Wu … (2010)
              Staging inadequately predicts metastatic risk in patients with colon cancer. We used a gene expression profile derived from invasive, murine colon cancer cells that were highly metastatic in an immunocompetent mouse model to identify patients with colon cancer at risk of recurrence. This phase 1, exploratory biomarker study used 55 patients with colorectal cancer from Vanderbilt Medical Center (VMC) as the training dataset and 177 patients from the Moffitt Cancer Center as the independent dataset. The metastasis-associated gene expression profile developed from the mouse model was refined with comparative functional genomics in the VMC gene expression profiles to identify a 34-gene classifier associated with high risk of metastasis and death from colon cancer. A metastasis score derived from the biologically based classifier was tested in the Moffitt dataset. A high score was significantly associated with increased risk of metastasis and death from colon cancer across all pathologic stages and specifically in stage II and stage III patients. The metastasis score was shown to independently predict risk of cancer recurrence and death in univariate and multivariate models. For example, among stage III patients, a high score translated to increased relative risk of cancer recurrence (hazard ratio, 4.7; 95% confidence interval, 1.566-14.05). Furthermore, the metastasis score identified patients with stage III disease whose 5-year recurrence-free survival was >88% and for whom adjuvant chemotherapy did not increase survival time. A gene expression profile identified from an experimental model of colon cancer metastasis predicted cancer recurrence and death, independently of conventional measures, in patients with colon cancer. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (iso-abbrev): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: MDPI
                ISSN (Electronic): 1422-0067
                Publication date (Electronic): 16 August 2018
                Publication date Collection: August 2018
                Volume: 19
                Issue: 8
                Electronic Location Identifier: 2413
                Affiliations
                [1 ]Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan
                [2 ]Department of Oral and Maxillofacial Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; tkirita@ 123456naramed-u.ac.jp
                Author notes
                [* ]Correspondence: sasa@ 123456naramed-u.ac.jp ; Tel.: +81-744-29-8849; Fax: +81-744-25-7308
                Author information
                https://orcid.org/0000-0003-1757-1275
                https://orcid.org/0000-0002-6900-0397
                Article
                Publisher ID: ijms-19-02413
                DOI: 10.3390/ijms19082413
                PMC ID: 6121568
                PubMed ID: 30115834
                SO-VID: 8e33a58a-3794-4ad3-bd94-1e9379c8a332
                Copyright © © 2018 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 28 July 2018
                Date accepted : 15 August 2018
                Categories
                Subject: Review

                ScienceOpen disciplines: Molecular biology
                Keywords: oral cancer,hallmarks of cancer,prognostic factors
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: oral cancer, hallmarks of cancer, prognostic factors

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