Genome-Wide Analysis Reveals Hypoxic Microenvironment Is Associated With Immunosuppression in Poor Survival of Stage II/III Colorectal Cancer Patients.
Genome-Wide Analysis Reveals Hypoxic Microenvironment Is Associated With Immunosuppression in Poor Survival of Stage II/III Colorectal Cancer Patients.
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DOI：
10.3389/fmed.2021.686885
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发表时间：
2021
影响因子：
3.9
通讯作者：
Gao F
中科院分区：
文献类型：
--
作者：
Chen YF;Yu ZL;Lv MY;Zheng B;Tan YX;Ke J;Liu XH;Cai ZR;Zou YF;Lan P;Wu XJ;Gao F
背景：缺氧与实体瘤较差的临床结果和化疗耐药性相关；识别缺氧相关结直肠癌（CRC）并揭示其机制非常重要。本研究的目的是评估缺氧特征以预测预后并分析相关机制。方法：选择未接受化疗的患者进行缺氧相关基因（HRG）的鉴定。总共包含 1,877 名 CRC 患者的 6 个独立数据集被分为一个训练队列和两个验证队列。进行功能注释和分析以揭示相关机制。结果：得出了 12 个基因特征，这对于两个验证队列中的 II/III 期 CRC 患者具有预后意义 [TCGA，n = 509，风险比 (HR) = 2.14，95% 置信区间 (CI) = 1.18 – 3.89，P = 0.01；元验证，n = 590，HR = 2.46，95% CI = 1.59 – 3.81，P < 0.001]。在未接受辅助化疗的 CRC 患者中，高缺氧风险与较差的预后相关（HR = 5.1，95% CI = 2.51 – 10.35，P < 0.001）。与临床特征整合后，缺氧相关基因特征（HRGS）在多变量分析中仍然是一个独立的预后因素。此外，富集分析发现，高缺氧组的抗肿瘤免疫反应受到抑制。结论：HRGS 是一种很有前景的评估 II/III 期 CRC 患者无病生存率的系统。缺氧的肿瘤微环境可能通过抑制免疫反应来促进II/III期CRC患者的化疗耐药。
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 < 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 < 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.
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影响因子：
37.3
作者：
Li Y;Liang L;Dai W;Cai G;Xu Y;Li X;Li Q;Cai S
通讯作者：
Cai S
影响因子：
8.8
作者：
Ragnum, H. B.;Vlatkovic, L.;Lie, A. K.;Axcrona, K.;Julin, C. H.;Frikstad, K. M.;Hole, K. H.;Seierstad, T.;Lyng, H.
通讯作者：
Lyng, H.
影响因子：
5.8
作者：
Liberzon, Arthur;Subramanian, Aravind;Mesirov, Jill P.
通讯作者：
Mesirov, Jill P.
DOI：
10.1073/pnas.0611662104
发表时间：
2007-05-29
影响因子：
11.1
作者：
Cairns, Rob A.;Papandreou, Ioanna;Denko, Nicholas C.
通讯作者：
Denko, Nicholas C.
DOI：
10.1158/1078-0432.ccr-13-0542
发表时间：
2013-09-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Eustace A;Mani N;Span PN;Irlam JJ;Taylor J;Betts GN;Denley H;Miller CJ;Homer JJ;Rojas AM;Hoskin PJ;Buffa FM;Harris AL;Kaanders JH;West CM
通讯作者：
West CM