Robust Glycogene-Based Prognostic Signature for Proficient Mismatch Repair Colorectal Adenocarcinoma
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Yixi Li, Dehua Li, Yang Chen, Yongping Lu, Fangbin Zhou, Chunhong Li, Zhipeng Zeng, Wanxia Cai, Liewen Lin, Qiang Li, Mingjun Ye, Jingjing Dong (+4 others)
Abstract
<jats:sec><jats:title>Background</jats:title>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.</jats:sec><jats:sec><jats:title>Methods</jats:title>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).</jats:sec><jats:sec><jats:title>Results</jats:title>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 (<jats:italic>B3GNT6</jats:italic>, <jats:italic>GALNT3</jats:italic>, <jats:italic>GALNT8</jats:italic>, <jats:italic>ALG8</jats:italic>, <jats:italic>STT3B</jats:italic>, <jats:italic>SRD5A3</jats:italic>, and <jats:italic>ALG6</jats:italic>) 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.</jats:sec><jats:sec><jats:title>Conclusions</jats:title>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.</jats:sec>
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