Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinoma.
Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinoma.
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DOI：
10.1016/j.ebiom.2021.103510
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发表时间：
2021-08
期刊：
影响因子：
11.1
通讯作者：
Lu C
中科院分区：
文献类型：
--
作者：
Li Y;Xu F;Chen F;Chen Y;Ge D;Zhang S;Lu C
食管鳞状细胞癌（ESCC）是恶性肿瘤中的一种。全面剖析ESCC的分子特征和异质性为开发更有前途的治疗方法铺平了道路。整合了多个ESCC数据集的表达谱。结合ATAC-seq和RNA-seq来揭示染色质可及性特征。构建了肿瘤相关亚型分类器（PrSC），并评估了其与肿瘤微环境（TME）和免疫治疗的相关性。在临床样品中验证了关键基因签名。基于ESCC患者的TME异质性，筛选潜在的亚型特异性治疗药物。筛选出食管鳞癌中常见的差异表达基因（cDEG）。发现上调基因（HEATR 1、TIMELESS、DTL、GINS 1、RUVBL 1和ECT 2）在ESCC细胞存活中非常重要。PRIM 2、HPGD、NELL 2和TFAP 2B的表达改变与染色质可及性变化相关。PrSC是一个可靠的评分工具，不仅与ESCC患者的预后相关，而且可以反映TME的异质性。TNS 1high成纤维细胞与免疫排斥有关。TG-101348和长春瑞滨被确定为潜在的亚型特异性治疗药物。此外，PrSC在两个免疫治疗队列中的应用表明其在评估对免疫治疗的治疗应答方面的潜在价值。我们的研究描述了ESCC的多维度特征，建立了一个强大的预后评估评分工具，强调了TNS 1high成纤维细胞在TME中的作用，并确定了临床使用的潜在药物。对本研究做出贡献的资助机构的完整列表可在鸣谢部分找到。
Esophageal squamous cell carcinoma (ESCC) remains one of the deadly cancer types. Comprehensively dissecting the molecular characterization and the heterogeneity of ESCC paves the way for developing more promising therapeutics. Expression profiles of multiple ESCC datasets were integrated. ATAC-seq and RNA-seq were combined to reveal the chromatin accessibility features. A prognosis-related subtype classifier (PrSC) was constructed, and its association with the tumor microenvironment (TME) and immunotherapy was assessed. The key gene signature was validated in clinical samples. Based on the TME heterogeneity of ESCC patients, potential subtype-specific therapeutic agents were screened. The common differentially expressed genes (cDEGs) in ESCC were identified. Up-regulated genes (HEATR1, TIMELESS, DTL, GINS1, RUVBL1, and ECT2) were found highly important in ESCC cell survival. The expression alterations of PRIM2, HPGD, NELL2, and TFAP2B were associated with chromatin accessibility changes. PrSC was a robust scoring tool that was not only associated with the prognosis of ESCC patients, but also could reflect the TME heterogeneity. TNS1high fibroblasts were associated with immune exclusion. TG-101348 and Vinorelbine were identified as potential subtype-specific therapeutic agents. Besides, the application of PrSC into two immunotherapy cohorts indicated its potential value in assessing treatment response to immunotherapy. Our study depicted the multi-dimensional characterization of ESCC, established a robust scoring tool for the prognosis assessment, highlighted the role of TNS1high fibroblasts in TME, and identified potential drugs for clinical use. A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
4
作者：
Duan J;Wang L;Shang L;Yang S;Wu H;Huang Y;Miao Y
通讯作者：
Miao Y
单细胞 RNA 测序强调了炎性癌症相关成纤维细胞在膀胱尿路上皮癌中的作用。
影响因子：
16.6
作者：
Chen Z;Zhou L;Liu L;Hou Y;Xiong M;Yang Y;Hu J;Chen K
通讯作者：
Chen K
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：
64.8
作者：
Ghandi, Mahmoud;Huang, Franklin W.;Sellers, William R.
通讯作者：
Sellers, William R.