PDF(Pubmed)
Abstract：
Cellular senescence (CS) is closely related to tumor progression. However, the studies about CS genes across human cancers have not explored the relationship between cancer senescence signature and telomere length. Additionally, single-cell analyses have not revealed the evolutionary trends of malignant cells and immune cells at the CS level. We defined a CS-associated signature, called \"senescence signature\", and found that patients with higher senescence signature had worse prognosis. Higher senescence signature was related to older age, higher genomic instability, longer telomeres, increased lymphocytic infiltration, higher pro-tumor immune infiltrates (Treg cells and MDSCs), and could predict responses to immune checkpoint inhibitor therapy. Single-cell analysis further reveals malignant cells and immune cells share a consistent evolutionary trend at the CS level. MAPK signaling pathway and apoptotic processes may play a key role in CS, and senescence signature may effectively predict sensitivity of MEK1/2 inhibitors, ERK1/2 inhibitors and BCL-2 family inhibitors. We also developed a new CS prediction model of cancer survival and established a portal website to apply this model ( https://bio-pub.shinyapps.io/cs_nomo/ ).
摘要：
细胞衰老(CS)与肿瘤进展密切相关。然而,关于人类癌症CS基因的研究尚未探讨癌症衰老特征与端粒长度之间的关系。此外,单细胞分析尚未揭示CS水平上恶性细胞和免疫细胞的进化趋势。我们定义了一个CS相关的签名，称为“衰老签名”，发现衰老特征较高的患者预后较差。较高的衰老特征与年龄有关，更高的基因组不稳定性，更长的端粒，淋巴细胞浸润增加，高亲肿瘤免疫浸润（Treg细胞和MDSCs），并可以预测对免疫检查点抑制剂治疗的反应。单细胞分析进一步揭示了恶性细胞和免疫细胞在CS水平上具有一致的进化趋势。MAPK信号通路和凋亡过程可能在CS,衰老特征可以有效预测MEK1/2抑制剂的敏感性，ERK1/2抑制剂和BCL-2家族抑制剂。我们还开发了一种新的癌症生存CS预测模型，并建立了一个门户网站来应用该模型（https://bio-pub。shinyapps.io/cs_nomo/)。
