Characterization of gastric cancer stem-like molecular features, immune and pharmacogenomic landscapes
Characterization of gastric cancer stem-like molecular features, immune and pharmacogenomic landscapes
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DOI：
10.1093/bib/bbab386
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发表时间：
2021-09
影响因子：
9.5
通讯作者：
Chen Wei;Mingkai Chen;W. Deng;L. Bie;Yijie Ma;Chi Zhang;Kangdong Liu;W. Shen;Shuyi Wang;Chaogang Yang;S. Luo;Ning Li
中科院分区：
文献类型：
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作者：
Chen Wei;Mingkai Chen;W. Deng;L. Bie;Yijie Ma;Chi Zhang;Kangdong Liu;W. Shen;Shuyi Wang;Chaogang Yang;S. Luo;Ning Li
癌症干细胞（CSC）主动重新编程其肿瘤微环境（TME）以维持支持性生态位，这可能对预后和免疫治疗产生巨大影响。然而，我们对胃癌干细胞样细胞（GCSC）微环境的认识需要进一步提高。进行了机器学习方法的多步骤过程，以开发和验证GCSC相关评分（GCScore）的预后和预测潜力。高GCS评分亚组不仅与干细胞特性有关，而且与潜在的免疫逃逸机制有关。此外，我们通过实验证明了CD206+肿瘤相关巨噬细胞（TAM）在浸润边缘区域的浸润上调，这反过来又维持了肿瘤细胞的干细胞特性。最后，我们提出GCScore显示出强大的免疫治疗预测能力，并研究了具有高GCScore的患者的潜在治疗靶点和化合物。结果表明，GCScore可以作为预测预后和免疫治疗反应的有效指标，为GCSCs的精确治疗提供了新的策略。
Cancer stem cells (CSCs) actively reprogram their tumor microenvironment (TME) to sustain a supportive niche, which may have a dramatic impact on prognosis and immunotherapy. However, our knowledge of the landscape of the gastric cancer stem-like cell (GCSC) microenvironment needs to be further improved. A multi-step process of machine learning approaches was performed to develop and validate the prognostic and predictive potential of the GCSC-related score (GCScore). The high GCScore subgroup was not only associated with stem cell characteristics, but also with a potential immune escape mechanism. Furthermore, we experimentally demonstrated the upregulated infiltration of CD206+ tumor-associated macrophages (TAMs) in the invasive margin region, which in turn maintained the stem cell properties of tumor cells. Finally, we proposed that the GCScore showed a robust capacity for prediction for immunotherapy, and investigated potential therapeutic targets and compounds for patients with a high GCScore. The results indicate that the proposed GCScore can be a promising predictor of prognosis and responses to immunotherapy, which provides new strategies for the precision treatment of GCSCs.