Charactering tumor microenvironment reveals stromal-related transcription factors promote tumor carcinogenesis in gastric cancer
Charactering tumor microenvironment reveals stromal-related transcription factors promote tumor carcinogenesis in gastric cancer
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肿瘤微环境特征揭示基质相关转录因子促进胃癌肿瘤发生
DOI：
10.1002/cam4.3133
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发表时间：
2020-05-28
期刊：
影响因子：
4
通讯作者：
Weng, Weiwei
中科院分区：
文献类型：
--
作者：
Liu, Haining;Ni, Shujuan;Weng, Weiwei
转录因子代表了控制基因转录在癌症发展和进展中的关键作用。然而，它们在胃癌中的功能尚未得到彻底的表征。在这项研究中，我们全面评估了肿瘤微环境（TME）细胞的浸润模式和TFs表达之间的相关性，在胃癌队列（STAD）从TCGA数据库。我们综合探讨了TCGA‐STAD队列中候选TF的差异表达组和预后价值。值得注意的是，我们发现了一个关键的转录因子命名为HEYL，其表达水平与TME的基质成分转化相关。HEYL在胃癌中呈规律性高表达，与患者预后不良相关。HEYL基因的敲除显著地消除了胃癌细胞增殖、迁移和进展的趋势。HEYL过表达可通过激活癌基因信号通路和钙粘蛋白11（CDH11）的转录激活而促进胃癌的发生发展。我们的研究结果不仅证实了TF与TME表型之间的密切关系，而且强调了TF的重要性，特别是HEYL，它可以被确定为评估胃癌预后风险和治疗效果的候选生物标志物。
Transcription factors represent the crucial role of controlling gene transcription in cancer development and progression. However, their functions in gastric cancer have not been thoroughly characterized. For this study, we comprehensively evaluated the correlation between infiltration patterns of tumor microenvironment (TME) cells and TFs expression in the cohort of stomach adenocarcinoma (STAD) from TCGA database. We integrally explored differential expression panel and prognostic value of candidate TFs in TCGA‐STAD cohort. Notably, we found a key transcription factor named HEYL, which its expression level was correlated with stromal component transformation of TME. HEYL was regularly high expressed in gastric cancer and correlated with patients’ poor prognosis. Knockdown of HEYL prominently abrogated the tendency of cell proliferation, migration, and progression in gastric cancer. Consistently, overexpression of HEYL strikingly accelerated the gastric carcinoma development through activating oncogenic signaling pathways and transcriptional activation of cadherin 11 (CDH11). Our findings not only identified the close relationship between TFs and TME phenotype, but also emphasized the crucial importance of TFs, especially HEYL, which could be identified as a candidate biomarker to evaluate prognostic risk and therapeutic effect in gastric cancer.