Abstract:
BACKGROUND:Colorectal cancer (CRC) has been divided into 4 consensus molecular subtypes (CMSs), of which CMS4 has the mesenchymal identity and the highest relapse rate. Our goal is to develop a prognostic signature by integrating the immune system and mesenchymal modalities involved in CMS4. METHODS:The gene expression profiles collected from 5 public datasets were applied to this study, including 1280 samples totally. Network analysis was applied to integrate the mesenchymal modalities and immune signature to establish an immune-based prognostic signature for CRC (IPSCRC). RESULTS:We identified 6 immune genes as key factors of CMS4 and established the IPSCRC. The IPSCRC could significantly divide patients into high- and low- risk groups in terms of relapse-free survival (RFS) and overall survival (OS) and in discovery (RFS: P < .0001) and 4 independent validation sets (RFS range: P = .01 to <.0001; OS range: P = .02-.0004). After stage stratification, the IPSCRC could still distinguish poor prognosis patients in discovery (RFS: P = .04) and validation cohorts (RFS range: P = .04-.007) within stage II in terms of RFS. Further, in multivariate analysis, the IPSCRC remained an independent predictor of prognosis. Moreover, Macrophage M2 was significantly enriched in the high-risk group, while plasma cells enriched in the low-risk group. CONCLUSION:We propose an immune-based signature identified by network analysis, which is a promising prognostic biomarker and help for the selection of CRC patients who might benefit from more rigorous therapies. Further prospective studies are warranted to test and validate its efficiency for clinical application.
journal_name
Medicine (Baltimore)journal_title
Medicineauthors
Zhang B,Wang L,Liu Z,Shao B,Jiang W,Shu Pdoi
10.1097/MD.0000000000020617subject
Has Abstractpub_date
2020-06-19 00:00:00pages
e20617issue
25eissn
0025-7974issn
1536-5964pii
00005792-202006190-00038journal_volume
99pub_type
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