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      CBX8 and CD96 Are Important Prognostic Biomarkers of Colorectal Cancer

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          Abstract

          Background

          Colorectal cancer (CRC) is one of the most common malignancies worldwide, with high morbidity and mortality rates. The purpose of this study was to identify potential biomarkers in the progression of CRC.

          Material/Methods

          Gene and isoform expression datasets of CRC was downloaded from The Cancer Genome Atlas (TCGA). EBSeq of R was used for the normalization of gene and isoform expression, as well as the identification of differential expression genes (DEGs) and isoforms (DEIs) of CRC samples compared with normal samples. The enriched functions of DEGs and DEIs were obtained based on the Database for Annotation, Visualization and Integrated Discovery (DAVID). An independent dataset, GSE38832, was downloaded from the Gene Expression Omnibus (GEO) database for survival analysis of genes with sustained decreased/increased expression values at both gene and isoform levels with the development of CRC.

          Results

          A total of 2301 genes and 4241 isoforms were found to be significantly differentially expressed in stage I–IV CRC samples. They are closely associated with muscle or cell system activity. Sixteen genes were screened out with sustained decreased/increased expression values at both gene and isoform levels with the development of CRC. Aberrant CBX8 and CD96 expressions were found to be significantly associated with CRC survival.

          Conclusions

          Through combined analysis of gene and isoform expression profiles, we identified several potential biomarkers that may play an important role in the development of CRC and could be helpful in its early diagnosis and treatment.

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          Most cited references28

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          The updated EAU guidelines on muscle-invasive and metastatic bladder cancer.

          New data regarding diagnosis and treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. To review the new EAU guidelines for MiM-BC. A comprehensive workup of the literature obtained from Medline, the Cochrane central register of systematic reviews, and reference lists in publications and review articles was developed and screened by a group of urologists, oncologists, and radiologist appointed by the EAU Guideline Committee. Previous recommendations based on the older literature on this subject were taken into account. Levels of evidence and grade of guideline recommendations were added, modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence. The diagnosis of muscle-invasive bladder cancer (BCa) is made by transurethral resection (TUR) and following histopathologic evaluation. Patients with confirmed muscle-invasive BCa should be staged by computed tomography (CT) scans of the chest, abdomen, and pelvis, if available. Adjuvant chemotherapy is currently only advised within clinical trials. Radical cystectomy (RC) is the treatment of choice for both sexes, and lymph node dissection should be an integral part of cystectomy. An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for clinical or personal reasons. An appropriate schedule for disease monitoring should be based on (1) natural timing of recurrence, (2) probability of disease recurrence, (3) functional deterioration at particular sites, and (4) consideration of treatment of a recurrence. In metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin is cisplatin-containing combination chemotherapy. Presently, there is no standard second-line chemotherapy. These EAU guidelines are a short, comprehensive overview of the updated guidelines of (MiM-BC) as recently published in the EAU guidelines and also available in the National Guideline Clearinghouse.
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            Estrogen receptor beta as target for colorectal cancer prevention.

            Colorectal cancer (CRC) is a leading cause of death in the United States. Despite its slow development and the capacity for early diagnosis, current preventive approaches are not sufficient. However, a role for estrogen has been demonstrated in multiple epidemiologic studies, which may benefit CRC prevention. A large body of evidence from preclinical studies indicates that expression of the estrogen receptor beta (ERβ/ESR2) demonstrates an inverse relationship with the presence of colorectal polyps and stage of tumors, and can mediate a protective response. Natural compounds, including phytoestrogens, or synthetic ERβ selective agonists, can activate or upregulate ERβ in the colon and promote apoptosis in preclinical models and in clinical experience. Importantly, this activity has been associated with a reduction in polyp formation and, in rodent models of CRC, has been shown to lower incidence of colon adenocarcinoma. Collectively, these findings indicate that targeted activation of ERβ may represent a novel clinical approach for management of colorectal adenomatous polyps and prevention of colorectal carcinoma in patients at risk for this condition. In this review, we discuss the potential of new chemopreventive or dietary approaches based on estrogen signaling.
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              Nuclear factor of activated T-cell activity is associated with metastatic capacity in colon cancer.

              Metastatic recurrence is the leading cause of cancer-related deaths in patients with colorectal carcinoma. To capture the molecular underpinnings for metastasis and tumor progression, we performed integrative network analysis on 11 independent human colorectal cancer gene expression datasets and applied expression data from an immunocompetent mouse model of metastasis as an additional filter for this biologic process. In silico analysis of one metastasis-related coexpression module predicted nuclear factor of activated T-cell (NFAT) transcription factors as potential regulators for the module. Cells selected for invasiveness and metastatic capability expressed higher levels of NFATc1 as compared with poorly metastatic and less invasive parental cells. We found that inhibition of NFATc1 in human and mouse colon cancer cells resulted in decreased invasiveness in culture and downregulation of metastasis-related network genes. Overexpression of NFATc1 significantly increased the metastatic potential of colon cancer cells, whereas inhibition of NFATc1 reduced metastasis growth in an immunocompetent mouse model. Finally, we found that an 8-gene signature comprising genes upregulated by NFATc1 significantly correlated with worse clinical outcomes in stage II and III colorectal cancer patients. Thus, NFATc1 regulates colon cancer cell behavior and its transcriptional targets constitute a novel, biologically anchored gene expression signature for the identification of colon cancers with high risk of metastatic recurrence.
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                Author and article information

                Journal
                Med Sci Monit
                Med. Sci. Monit
                Medical Science Monitor
                Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
                International Scientific Literature, Inc.
                1234-1010
                1643-3750
                2018
                01 November 2018
                : 24
                : 7820-7827
                Affiliations
                Department of General Surgery, China-Japan Friendship Hospital, Beijing, P.R. China
                Author notes
                Corresponding Author: Lei Zhou, e-mail: leizhouzr@ 123456126.com
                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                Article
                908656
                10.12659/MSM.908656
                6225733
                30383736
                b380065e-2412-4e99-a896-2e7a7a14f91d
                © Med Sci Monit, 2018

                This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International ( CC BY-NC-ND 4.0)

                History
                : 22 December 2017
                : 28 June 2018
                Categories
                Lab/In Vitro Research

                colorectal neoplasms,gene expression,protein interaction maps,survival analysis

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