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Metastasis-associated in colon cancer 1: A promising biomarker for the metastasis and prognosis of colorectal cancer.

ABSTRACT: Colorectal cancer (CRC) is the fourth most frequent type of malignancy in the world. Metastasis accounts for >90% mortalities in patients with CRC. The metastasis-associated in colon cancer 1 (MACC1) gene has been identified as a novel biomarker for the prediction of metastasis and disease prognosis, particularly for patients with early-stage disease. Previous clinical studies demonstrated that MACC1 expression and polymorphisms in CRC tissues were indicators of metastasis, and that circulating transcripts in plasma were also significantly associated with the survival of patients. The present review describes the use of MACC1 beyond its utility in the clinic. By elucidating the upstream and downstream signal pathways of MACC1, the well-known mechanisms of MACC1-mediated cell proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) are summarized, as well as the potential signaling pathways. Furthermore, the underlying mechanisms by which the overexpression of MACC1 causes cisplatin resistance are emphasized.

SUBMITTER: Li H

PROVIDER: S-EPMC5605967 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Metastasis-associated in colon cancer 1: A promising biomarker for the metastasis and prognosis of colorectal cancer.

Li He H Chen Yi-Xin YX Wen Jia-Gen JG Zhou Hong-Hao HH

Oncology letters 20170726 4

Colorectal cancer (CRC) is the fourth most frequent type of malignancy in the world. Metastasis accounts for >90% mortalities in patients with CRC. The metastasis-associated in colon cancer 1 (MACC1) gene has been identified as a novel biomarker for the prediction of metastasis and disease prognosis, particularly for patients with early-stage disease. Previous clinical studies demonstrated that MACC1 expression and polymorphisms in CRC tissues were indicators of metastasis, and that circulating ...[more]

PMID: 28943898

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Project description:Background: Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Lymph node metastasis (LNM) is a common mode of metastasis of CRC. However, the combined mRNA biomarkers associated with LNM of CRC that can effectively predict CRC prognosis have not been reported yet. Methods: To identify biomarkers that are associated with LNM, we collected data from the The Cancer Genome Atlas (TCGA) database. The edgeR package was searched to seek LNM-related genes by comparisons between cancer samples and normal colorectal tissues and between LNM and non-LNM (NLNM) of CRC. Univariate and multivariate regression analysis of genes in the intersection to build gene signature associated with independent prognosis of CRC, and then verified by Kaplan-Meier curve and log-rank test, receiver operating characteristic (ROC) curve was used to determine the efficiency of survival prediction of our four-mRNA signature. Finally, the potential molecular mechanisms and properties of these gene signature were also explored with functional and pathway enrichment analysis. Results: 329 mRNAs were up-regulated in CRC tissues with LNM, and 8461 mRNAs were up-regulated in CRC tissues, the intersection is 100 mRNAs. After univariate and multivariate Cox regression analysis of 100 mRNAs, a novel four LNM related mRNAs (EPHA8, KRT85, GABRA3, and CLPSL1) were screened as independent prognostic indicators of CRC. Surprisingly, the four-mRNA signature can predict the prognosis of CRC patients independently of clinical factors andthe area under the curve (AUC) of the ROC is 0.730. The novel four-mRNA signature was used to identify high and low-risk groups. Stratified analysis indicated the risk score based on four-mRNA signature was an independent prognostic indicator for female, T3+T4, N1+N2 ,stage III+IV and patients with no new tumor event. Functional annotation of this risk model in high-risk patients revealed that pathways associated with neuroactive ligand-receptor interaction, estrogen signaling pathway, and steroid hormone biosynthesis. Conclusions: By conducting TCGA data mining, our study demonstrated that a four-mRNA signature associated with LNM can be used as a combined biomarker for independent prognosis of CRC.

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Metastasis-associated in colon cancer 1: A promising biomarker for the metastasis and prognosis of colorectal cancer.

Publications

Metastasis-associated in colon cancer 1: A promising biomarker for the metastasis and prognosis of colorectal cancer.

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