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      Colon cancer recurrence-associated genes revealed by WGCNA co-expression network analysis

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          Abstract

          The present study aimed to identify the recurrence-associated genes in colon cancer, which may provide theoretical evidence for the development of novel methods to prevent tumor recurrence. Colon cancer and matched normal samples microarray data (E-GEOD-39582) were downloaded from ArrayExpress. Genes with significant variation were identified, followed by the screening of differentially expressed genes (DEGs). Subsequently, the co-expression network of DEGs was constructed using the weighted correlation network analysis (WGCNA) method, which was verified using the validation dataset. The significant modules associated with recurrence in the network were subsequently screened and verified in another independent dataset E-GEOD-33113. Function and pathway enrichment analyses were also conducted to determine the roles of selected genes. Survival analysis was performed to identify the association between these genes and survival. A total of 434 DEGs were identified in the colon samples, and stress-associated endoplasmic reticulum protein family member 2 (SERP2) and long non-coding RNA-0219 (LINC0219) were determined to be the vital DEGs between all the three sub-type groups with different clinical features. The brown module was identified to be the most significant module in the co-expression network associated with the recurrence of colon cancer, which was verified in the E-GEOD-33113 dataset. Top 10 genes in the brown module, including EGF containing fibulin like extracellular matrix protein 2 (EFEMP2), fibrillin 1 (FBN1) and secreted protein acidic and cysteine rich (SPARC) were also associated with survival time of colon cancer patients. Further analysis revealed that the function of cell adhesion, biological adhesion, extracellular matrix (ECM) organization, pathways of ECM-receptor interaction and focal adhesion were the significantly changed terms in colon cancer. In conclusion, SERP2, EFEMP2, FBN1, SPARC, and LINC0219 were revealed to be the recurrence-associated molecular and prognostic indicators in colon cancer by WGCNA co-expression network analysis.

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          Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity.

          Colon carcinoma is one of the leading causes of death from cancer and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, it was reported that a population of undifferentiated cells from a primary tumor, so-called cancer stem cells (CSC), can reconstitute the original tumor on xenotransplantation. Here, we show that spheroid cultures of these colon CSCs contain expression of CD133, CD166, CD44, CD29, CD24, Lgr5, and nuclear beta-catenin, which have all been suggested to mark the (cancer) stem cell population. More importantly, by using these spheroid cultures or freshly isolated tumor cells from multiple colon carcinomas, we now provide compelling evidence to indicate that the capacity to propagate a tumor with all differentiated progeny resides in a single CSC. Single-cell-cloned CSCs can form an adenocarcinoma on xenotransplantation but do not generate the stroma within these tumors. Moreover, they can self-renew and are capable of multilineage differentiation. Further analysis indicated that the lineage decision is dictated by phosphoinositide 3-kinase (PI3K) signaling in CSCs. These data support the hypothesis that tumor hierarchy can be traced back to a single CSC that contains multilineage differentiation capacity, and provides clues to the regulation of differentiation in colon cancers in vivo.
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            Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update

            Biomarkers currently play an important role in the detection and management of patients with several different types of gastrointestinal cancer, especially colorectal, gastric, gastro-oesophageal junction (GOJ) adenocarcinomas and gastrointestinal stromal tumors (GISTs). The aim of this article is to provide updated and evidence-based guidelines for the use of biomarkers in the different gastrointestinal malignancies. Recommended biomarkers for colorectal cancer include an immunochemical-based fecal occult blood test in screening asymptomatic subjects ≥50 years of age for neoplasia, serial CEA levels in postoperative surveillance of stage II and III patients who may be candidates for surgical resection or systemic therapy in the event of distant metastasis occurring, K-RAS mutation status for identifying patients with advanced disease likely to benefit from anti-EGFR therapeutic antibodies and microsatellite instability testing as a first-line screen for subjects with Lynch syndrome. In advanced gastric or GOJ cancers, measurement of HER2 is recommended in selecting patients for treatment with trastuzumab. For patients with suspected GIST, determination of KIT protein should be used as a diagnostic aid, while KIT mutational analysis may be used for treatment planning in patients with diagnosed GISTs.
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              Overexpression of long noncoding RNA PCAT-1 is a novel biomarker of poor prognosis in patients with colorectal cancer.

              Long noncoding RNAs (lncRNA) are emerging as key molecules in human cancer. Prostate cancer-associated ncRNA transcripts 1 (PCAT-1), a lncRNA, has been recently revealed involving in human prostate cancer progression. However, whether PCAT-1 could serve as novel biomarker to predict prognosis in colorectal cancer (CRC) or not is unknown. We therefore carried out the present study to explore the correlation between PCAT-1 expression and the progression of CRC. In this study, the expression of PCAT-1 in 108 cases of CRC tissues and matched 81 adjacent normal tissues were determined by quantitative real-time PCR. Furthermore, the copy number variation of PCAT-1 was also measured in 17 tumor tissues and matched normal tissues. Our results showed that PCAT-1 expression in CRC tissues was significantly upregulated compared with the matched normal tissues (p < 0.001) and the overexpression of PCAT-1(upregulated by more than 50 %) was found in 64 % (62/81) of CRC. Moreover, PCAT-1 gene copy number variation explains only a few percent of observed overexpression. In addition, there was a significant association between PCAT-1 expression and distant metastasis (p = 0.04), but not other clinical characteristics. More important, CRC patients with PCAT-1 higher expression have shown significantly poorer overall survival than those with lower PCAT-1 expression (p < 0.001). Also, multivariable Cox regression analysis identified PCAT-1 overexpression as an independent prognostic factor for CRC (p = 0.007, HR = 3.12 95 %CI = 1.355-7.185). In conclusion, our results suggest that high expression of PCAT-1 is involved in CRC progression and could be a novel biomarker of poor prognosis in patient with colorectal cancer.
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                Author and article information

                Journal
                Mol Med Rep
                Mol Med Rep
                Molecular Medicine Reports
                D.A. Spandidos
                1791-2997
                1791-3004
                November 2017
                31 August 2017
                31 August 2017
                : 16
                : 5
                : 6499-6505
                Affiliations
                [1 ]Department of Integrative Oncology, Changhai Hospital of Traditional Chinese Medicine, Second Military Medical University, Shanghai 200433, P.R. China
                [2 ]Department of Integrative Oncology, Changhai Hospital, Shanghai 200433, P.R. China
                [3 ]Department of Anesthesiology, 264 Hospital of The People's Liberation Army, Taiyuan, Shanxi 030001, P.R. China
                Author notes
                Correspondence to: Dr Zhe Chen, Department of Integrative Oncology, Changhai Hospital, 168 Changhai Road, Shanghai 200433, P.R. China, E-mail: chendhdhd@ 123456163.com
                [*]

                Contributed equally

                Article
                mmr-16-05-6499
                10.3892/mmr.2017.7412
                5865817
                28901407
                34a71789-3356-4bee-900f-35ad634d012b
                Copyright: © Zhai et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 31 March 2016
                : 20 March 2017
                Categories
                Articles

                colon cancer,co-expression,differentially expressed genes,recurrence,survival

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