无锚定凋亡和自噬相关基因特征可预测结肠癌的生存和肿瘤细胞进展。
Anoikis and Mitophagy-Related Gene Signature for Predicting the Survival and Tumor Cell Progression in Colon Cancer.
机构信息
Beijing Chao-Yang Hospital, Capital Medical University.
Department of General Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.
出版信息
Crit Rev Immunol. 2025;45(1):1-13. doi: 10.1615/CritRevImmunol.2024053203.
Anoikis is a specialized form of programmed cell death and is also related mitophagy process. We aimed to identify an anoikis and mitophagy-related genes (AMRGs) prognostic model and explore the role of SPHK1 in colon cancer (CC). Bioinformatic methods were used to screen the AMRGs. Based on these genes, all the samples were divided into different subtypes. Furthermore, LASSO was conducted to optimize the AMRGs. Based on the optimal genes, a prognostic risk score model was established and evaluated. Finally, the effects of downregulated SPHK1 on the CC cell proliferation, migration, invasion, and anoikis were investigated. Based on the AMRGs, all the CC samples were divided into subtype 1 and subtype 2. An AMRGs signature containing three key genes (SPHK1, CDC25C, and VPS37A) that exhibiting predicting ability in CC survival is confirmed. Subtype2 and low-risk groups exhibited better survival and higher immune cell infiltration. Moreover, downregulated SPHK1 is related to lower cell proliferation, migration, and invasion ability, as well as higher anoikis in CC cell line (P < 0.01). The AMRGs risk score model exhibits promising predicting ability on patients with CC. SPHK1 might inhibit CC cell growth, migration, and invasion through stimulating anoikis.
细胞失巢凋亡是一种特殊的程序化细胞死亡形式，也与线粒体自噬过程有关。我们旨在确定与细胞失巢凋亡和线粒体自噬相关的基因（AMRGs）预后模型，并探讨 SPHK1 在结肠癌（CC）中的作用。采用生物信息学方法筛选 AMRGs。基于这些基因，将所有样本分为不同的亚型。进一步采用 LASSO 对 AMRGs 进行优化。基于最优基因，建立并评估预后风险评分模型。最后，研究下调 SPHK1 对 CC 细胞增殖、迁移、侵袭和失巢凋亡的影响。基于 AMRGs，将所有 CC 样本分为亚型 1 和亚型 2。确认了一个包含三个关键基因（SPHK1、CDC25C 和 VPS37A）的 AMRGs 特征，这些基因在 CC 生存中具有预测能力。亚型 2 和低风险组表现出更好的生存和更高的免疫细胞浸润。此外，下调 SPHK1 与 CC 细胞系中较低的细胞增殖、迁移和侵袭能力以及较高的失巢凋亡有关（P < 0.01）。AMRGs 风险评分模型对 CC 患者具有良好的预测能力。SPHK1 可能通过刺激失巢凋亡来抑制 CC 细胞的生长、迁移和侵袭。
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