AUTHOR=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 

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

JOURNAL=Frontiers in Oncology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.727752

DOI=10.3389/fonc.2021.727752

ISSN=2234-943X

ABSTRACT=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-seq for 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 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 prognose poor-prognostic subtype for pMMR CRAC patients. This biomarker set was validated in multi-center 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