Molecular subtype identification and prognosis stratification by a metabolism-related gene expression signature in colorectal cancer.
Molecular subtype identification and prognosis stratification by a metabolism-related gene expression signature in colorectal cancer.
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通过结直肠癌代谢相关基因表达特征进行分子亚型鉴定和预后分层
DOI：
10.1186/s12967-021-02952-w
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发表时间：
2021-06-30
影响因子：
7.4
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Lin D;Fan W;Zhang R;Zhao E;Li P;Zhou W;Peng J;Li L
在肿瘤免疫微环境中，代谢再编程与肿瘤的发生和发展有关。然而，代谢相关基因在结直肠癌(CRC)中的预后潜能尚未得到全面的研究。在这里，我们研究了代谢转录相关的CRC亚型和相关的免疫环境，并开发了用于预测生存的代谢风险评分(MRS)。从分子签名数据库中收集代谢相关基因，并根据GSE39582中与生存相关的代谢基因的表达谱，使用非监督聚类算法识别代谢亚型。应用SSGSEA和ESTIMATION方法估计各亚型间的免疫渗入。MRS模型是在GSE39582数据集中使用套索Cox回归开发的，并在TCGA CRC和GSE17537数据集中独立验证。我们根据539个与生存相关的代谢基因的表达谱确定了两种与代谢相关的结直肠癌亚型(簇-A和簇-B)，这些基因具有不同的免疫学特征和显著不同的预后。与群集A子类型相比，群集B子类型的操作系统和RFS更短。在GSE39582中，18个主要参与脂类代谢途径的代谢相关基因被用来构建MRS。MRS高的患者预后比MRS低的患者差(HR3.45，P <； 0.001)。MRS在TCGA CRC(HR2.12，P = 0.00017)和GSE17537数据集(HR2.67，P = 0.039)中的预后作用得到验证。时间依赖的接收器工作特征曲线和分层分析表明，MRS在每个数据集中具有稳健的预测能力。多因素COX回归分析表明，MRS可以独立于TNM分期和年龄预测OS。我们的研究为了解结直肠癌的代谢异质性及其与免疫状况的关系提供了新的视角。MRS被认为是一个强有力的预后标志物，可能有助于结直肠癌患者的个体化治疗。网上版载有补充材料，可在10.1186/s12967021-02952-w查阅。
Metabolic reprograming have been associated with cancer occurrence and progression within the tumor immune microenvironment. However, the prognostic potential of metabolism-related genes in colorectal cancer (CRC) has not been comprehensively studied. Here, we investigated metabolic transcript-related CRC subtypes and relevant immune landscapes, and developed a metabolic risk score (MRS) for survival prediction. Metabolism-related genes were collected from the Molecular Signatures Database and metabolic subtypes were identified using an unsupervised clustering algorithm based on the expression profiles of survival-related metabolic genes in GSE39582. The ssGSEA and ESTIMATE methods were applied to estimate the immune infiltration among subtypes. The MRS model was developed using LASSO Cox regression in the GSE39582 dataset and independently validated in the TCGA CRC and GSE17537 datasets. We identified two metabolism-related subtypes (cluster-A and cluster-B) of CRC based on the expression profiles of 539 survival-related metabolic genes with distinct immune profiles and notably different prognoses. The cluster-B subtype had a shorter OS and RFS than the cluster-A subtype. Eighteen metabolism-related genes that were mostly involved in lipid metabolism pathways were used to build the MRS in GSE39582. Patients with higher MRS had worse prognosis than those with lower MRS (HR 3.45, P < 0.001). The prognostic role of MRS was validated in the TCGA CRC (HR 2.12, P = 0.00017) and GSE17537 datasets (HR 2.67, P = 0.039). Time-dependent receiver operating characteristic curve and stratified analyses revealed the robust predictive ability of the MRS in each dataset. Multivariate Cox regression analysis indicted that the MRS could predict OS independent of TNM stage and age. Our study provides novel insight into metabolic heterogeneity and its relationship with immune landscape in CRC. The MRS was identified as a robust prognostic marker and may facilitate individualized therapy for CRC patients. The online version contains supplementary material available at 10.1186/s12967-021-02952-w.
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影响因子：
16.6
作者：
Koyama S;Akbay EA;Li YY;Herter-Sprie GS;Buczkowski KA;Richards WG;Gandhi L;Redig AJ;Rodig SJ;Asahina H;Jones RE;Kulkarni MM;Kuraguchi M;Palakurthi S;Fecci PE;Johnson BE;Janne PA;Engelman JA;Gangadharan SP;Costa DB;Freeman GJ;Bueno R;Hodi FS;Dranoff G;Wong KK;Hammerman PS
通讯作者：
Hammerman PS
RNA序列和微阵列数据的联合分析揭示了神经母细胞瘤基于代谢的有效预后特征
影响因子：
5.3
作者：
Meng X;Feng C;Fang E;Feng J;Zhao X
通讯作者：
Zhao X
表观遗传上调的癌蛋白 PLCE1 通过激活 PI-PLC epsilon-NF-B 信号通路和 VEGF-C/Bcl-2 表达来驱动食管癌血管生成和增殖
影响因子：
37.3
作者：
Chen, Yunzhao;Wang, Dandan;Li, Feng
通讯作者：
Li, Feng
影响因子：
3.7
作者：
Parry M;Rose-Zerilli MJ;Gibson J;Ennis S;Walewska R;Forster J;Parker H;Davis Z;Gardiner A;Collins A;Oscier DG;Strefford JC
通讯作者：
Strefford JC
影响因子：
2
作者：
Kang, Le;Chen, Weijie;Petrick, Nicholas A.;Gallas, Brandon D.
通讯作者：
Gallas, Brandon D.