Expression pattern of secretory-cell-related transcriptional signatures in colon adenocarcinomas defines tumor microenvironment characteristics and correlates with clinical outcomes.
Expression pattern of secretory-cell-related transcriptional signatures in colon adenocarcinomas defines tumor microenvironment characteristics and correlates with clinical outcomes.
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DOI：
10.1002/1878-0261.13338
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发表时间：
2023-03
影响因子：
6.6
通讯作者：
Liao, Wangjun
中科院分区：
文献类型：
--
作者：
Zhou, Rui;Li, Lingbo;Xi, Shaoyan;Zhang, Yue;Liu, Zhihong;Zeng, Dongqiang;Sun, Huiying;Wu, Jianhua;Wang, Ling;Shi, Min;Bin, Jianping;Liao, Yulin;Liao, Wangjun
尽管分泌细胞与不同的含粘液的结肠癌组织学亚型存在联系，并且分泌细胞与免疫细胞在肠道炎症性疾病发病机制中的相互作用，但分泌细胞特征是否与肿瘤微环境（TME）异质性相关，并有助于结肠癌患者分类尚未研究。在这里，通过进行主成分分析和共识聚类分析，我们确定了四个不同的表达模式的基础上分泌细胞的签名，这是显着相关的不同的临床行为，TME景观，途径激活，基因组突变，和DNA甲基化特征。随后，构建了“SCS评分”模型。高SCS评分表明“分泌细胞亚型2”的模式，其特征在于基质浸润和活化，并预测预后不良和对基于氟尿嘧啶的化疗和免疫治疗的敏感性低，但对PI3K催化亚基抑制剂的敏感性高。总之，我们的研究全面揭示了与分泌细胞特征表达模式相关的肿瘤异质性。此外，SCS评分可以补充常规组织病理学评估，以指导结肠癌患者的个性化治疗策略。根据分泌细胞相关特征，结肠癌患者可分为4种亚型，这些亚型与不同的临床行为、免疫景观、通路激活、基因组突变和DNA甲基化特征显著相关。此外，我们建立了一个来自分泌细胞亚型的七基因评分模型，可用于结肠癌患者的预后和治疗益处预测。
Despite the connection of secretory cells to distinct mucus‐containing colon cancer histological subtypes and the interaction of secretory cells with immune cells in the pathogenesis of intestinal inflammatory diseases, whether the secretory cell signatures are associated with tumor microenvironment (TME) heterogeneity and can aid in colon cancer patient classification have not been investigated. Here, by performing the principal component analysis and consensus clustering analysis, we identified four distinct expression patterns based on secretory cell signatures which were significantly associated with different clinical behaviors, TME landscape, pathway activation, genomic mutations, and DNA methylation characteristics. Subsequently, a ‘SCS score’ model was constructed. The high SCS score indicated a pattern of ‘secretory cell subtype 2’, which was characterized by stromal infiltration and activation, and predicted poor prognosis and low sensitivity to fluorouracil‐based chemotherapy and immunotherapy, but high sensitivity to PI3K catalytic subunit inhibitors. In conclusion, our study comprehensively uncovered the tumor heterogeneity related to secretory cell signature expression patterns. Moreover, the SCS score can supplement routine histopathological assessments to guide personalized therapeutic strategies in colon cancer patients. Colon cancer patients could be classified into four subtypes, which were significantly associated with different clinical behaviors, immune landscape, pathway activation, genomic mutations, and DNA methylation characteristics, based on secretory‐cell‐related signatures. Additionally, we established a seven gene scoring model derived from secretory cell subtypes that could be used for prognosis and therapeutic benefit prediction in colon cancer patients.
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影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
14.9
作者：
Colaprico A;Silva TC;Olsen C;Garofano L;Cava C;Garolini D;Sabedot TS;Malta TM;Pagnotta SM;Castiglioni I;Ceccarelli M;Bontempi G;Noushmehr H
通讯作者：
Noushmehr H
影响因子：
21.3
作者：
Gao, Shuai;Yan, Liying;Tang, Fuchou
通讯作者：
Tang, Fuchou
乳腺癌中免疫浸润及其临床意义的模式：一项基于基因表达的回顾性研究。
影响因子：
15.8
作者：
Ali HR;Chlon L;Pharoah PD;Markowetz F;Caldas C
通讯作者：
Caldas C
影响因子：
3.5
作者：
Betge, Johannes;Schneider, Nora I.;Harbaum, Lars;Pollheimer, Marion J.;Lindtner, Richard A.;Kornprat, Peter;Ebert, Matthias P.;Langner, Cord
通讯作者：
Langner, Cord