State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China.
Front Immunol. 2023 Sep 26;14:1265911. doi: 10.3389/fimmu.2023.1265911. eCollection 2023.
Colorectal cancer (CRC) remains a primary cause of cancer mortality globally, necessitating precise prognostic indicators for effective clinical management. Our study introduces the Senescence Risk Score (SRRS), based on several senescence-related genes (SRGs), a potent prognostic tool designed to measure cellular senescence in CRC. The higher SRRS predicts a poorer prognosis, providing a novel and efficient approach to patient stratification. Notably, we found that SRRS correlates with methylation and mutation variations, and increased immune infiltration in the tumor microenvironment, thus revealing potential therapeutic targets. We also discovered an inverse relationship between SRRS and cell stemness, which could have significant implications for cancer treatment strategies. Utilizing bioinformatics resources and machine learning, we identified LIMK1 and WRN as key genes associated with SRRS, further enhancing its prognostic value. Importantly, the modulation of these genes significantly impacts cellular senescence, proliferation, and stemness in CRC cells. In summary, our development of SRRS offers a powerful tool for CRC prognosis and paves the way for novel therapeutic strategies, underscoring its potential in transforming CRC patient management.
结直肠癌(CRC)仍然是全球癌症死亡的主要原因,因此需要精确的预后指标来进行有效的临床管理。我们的研究提出了 Senescence Risk Score(SRRS),它基于几个与衰老相关的基因(SRGs),是一种强大的预后工具,旨在衡量 CRC 中的细胞衰老。较高的 SRRS 预示着更差的预后,为患者分层提供了一种新颖有效的方法。值得注意的是,我们发现 SRRS 与甲基化和突变变异以及肿瘤微环境中的免疫浸润增加相关,从而揭示了潜在的治疗靶点。我们还发现 SRRS 与细胞干性呈负相关,这可能对癌症治疗策略有重大影响。我们利用生物信息学资源和机器学习,确定了 LIMK1 和 WRN 是与 SRRS 相关的关键基因,进一步增强了其预后价值。重要的是,这些基因的调节显著影响 CRC 细胞中的细胞衰老、增殖和干性。总之,我们开发的 SRRS 为 CRC 的预后提供了一个强大的工具,并为新的治疗策略铺平了道路,突显了其在改变 CRC 患者管理方面的潜力。