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Robust Glycogene-Based Prognostic Signature for Proficient Mismatch Repair Colorectal Adenocarcinoma.

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机构: [1]Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Jinan University, Shenzhen, China [2]Institute of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China [3]Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes and MOE Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, Jinan University, Guangzhou, China [4]Department of Nephrology, Dongguan Hospital of Guangzhou University of Traditional Chinese Medicine, Dongguan, China [5]Guangxi Key Laboratory of Metabolic Diseases Research, Affiliated No. 924 Hospital, Southern Medical University, Guilin, China
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关键词: colorectal cancer mismatch repair glycosylation glycogene ceRNA biomarker

摘要:
Proficient mismatch repair (pMMR) colorectal adenocarcinoma (CRAC) metastasizes to a greater extent than MMR-deficient CRAC. Prognostic biomarkers are preferred in clinical practice. However, traditional biomarkers screened directly from sequencing are often not robust and thus cannot be confidently utilized.To circumvent the drawbacks of blind screening, we established a new strategy to identify prognostic biomarkers in the conserved and specific oncogenic pathway and its regulatory RNA network. We performed RNA sequencing (RNA-seq) for messenger RNA (mRNA) and noncoding RNA in six pMMR CRAC patients and constructed a glycosylation-related RNA regulatory network. Biomarkers were selected based on the network and their correlation with the clinicopathologic information and were validated in multiple centers (n = 775).We constructed a competing endogenous RNA (ceRNA) regulatory network using RNA-seq. Genes associated with glycosylation pathways were embedded within this scale-free network. Moreover, we further developed and validated a seven-glycogene prognosis signature, GlycoSig (B3GNT6, GALNT3, GALNT8, ALG8, STT3B, SRD5A3, and ALG6) that prognosticate poor-prognostic subtype for pMMR CRAC patients. This biomarker set was validated in multicenter datasets, demonstrating its robustness and wide applicability. We constructed a simple-to-use nomogram that integrated the risk score of GlycoSig and clinicopathological features of pMMR CRAC patients.The seven-glycogene signature served as a novel and robust prognostic biomarker set for pMMR CRAC, highlighting the role of a dysregulated glycosylation network in poor prognosis.Copyright © 2021 Li, Li, Chen, Lu, Zhou, Li, Zeng, Cai, Lin, Li, Ye, Dong, Yin, Tang, Zhang and Dai.

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出版当年[2020]版:
大类 | 2 区 医学
小类 | 3 区 肿瘤学
最新[2025]版:
大类 | 3 区 医学
小类 | 4 区 肿瘤学
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出版当年[2019]版:
Q2 ONCOLOGY
最新[2023]版:
Q2 ONCOLOGY

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第一作者机构: [1]Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Jinan University, Shenzhen, China [2]Institute of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
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通讯机构: [1]Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Jinan University, Shenzhen, China [5]Guangxi Key Laboratory of Metabolic Diseases Research, Affiliated No. 924 Hospital, Southern Medical University, Guilin, China
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