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

作者：Li, Yixi; Li, Dehua; Chen, Yang; Lu, Yongping; Zhou, Fangbin; Li, Chunhong; Zeng, Zhipeng; Cai, Wanxia; Lin, Liewen; Li, Qiang; Ye, Mingjun; Dong, Jingjing; Yin, Lianghong^*; Tang, Donge^*; Zhang, Gong^*; Dai, Yong^*

来源：Frontiers in Oncology, 2021, 11: 727752.

DOI：10.3389/fonc.2021.727752

• colorectal cancer
• mismatch repair
• glycosylation
• glycogene
• ceRNA
• biomarker

Background @@@ 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. @@@ Methods @@@ 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). @@@ Results @@@ 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. @@@ Conclusions @@@ 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.

• 单位
  1; 南方医科大学; y; 广州中医药大学