In:
Frontiers in Medicine, Frontiers Media SA, Vol. 8 ( 2021-6-15)
Abstract:
Background: Hypoxia is associated with a poorer clinical outcome and resistance to chemotherapy in solid tumors; identifying hypoxic-related colorectal cancer (CRC) and revealing its mechanism are important. The aim of this study was to assess hypoxia signature for predicting prognosis and analyze relevant mechanism. Methods: Patients without chemotherapy were selected for the identification of hypoxia-related genes (HRGs). A total of six independent datasets that included 1,877 CRC patients were divided into a training cohort and two validation cohorts. Functional annotation and analysis were performed to reveal relevant mechanism. Results: A 12-gene signature was derived, which was prognostic for stage II/III CRC patients in two validation cohorts [TCGA, n = 509, hazard ratio (HR) = 2.14, 95% confidence interval (CI) = 1.18 – 3.89, P = 0.01; metavalidation, n = 590, HR = 2.46, 95% CI = 1.59 – 3.81, P & lt; 0.001]. High hypoxic risk was correlated with worse prognosis in CRC patients without adjuvant chemotherapy (HR = 5.1, 95% CI = 2.51 – 10.35, P & lt; 0.001). After integration with clinical characteristics, hypoxia-related gene signature (HRGS) remained as an independent prognostic factor in multivariate analysis. Furthermore, enrichment analysis found that antitumor immune response was suppressed in the high hypoxic group. Conclusions: HRGS is a promising system for estimating disease-free survival of stage II/III CRC patients. Hypoxia tumor microenvironment may be via inhibiting immune response to promote chemoresistance in stage II/III CRC patients.
Type of Medium:
Online Resource
ISSN:
2296-858X
DOI:
10.3389/fmed.2021.686885
DOI:
10.3389/fmed.2021.686885.s001
DOI:
10.3389/fmed.2021.686885.s002
DOI:
10.3389/fmed.2021.686885.s003
DOI:
10.3389/fmed.2021.686885.s004
DOI:
10.3389/fmed.2021.686885.s005
DOI:
10.3389/fmed.2021.686885.s006
DOI:
10.3389/fmed.2021.686885.s007
DOI:
10.3389/fmed.2021.686885.s008
DOI:
10.3389/fmed.2021.686885.s009
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2021
detail.hit.zdb_id:
2775999-4
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