Li Guangyao, Wang Pingyu, Feng Xiangnan, Li Yongxiang
Department of General Surgery, The First Afliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China.
Department of Gastrointestinal Surgery, The Second People's Hospital of Wuhu, Wuhu, 241000, Anhui, China.
Discov Oncol. 2024 Dec 18;15(1):787. doi: 10.1007/s12672-024-01691-w.
Pyroptosis, an emerging type of programmed cell death. The mechanisms of pyroptosis mainly include inflammasome-activated pyroptosis and non-inflammasome-activated pyroptosis. Multiple prognostic scoring systems that utilize pyroptosis-related gene expression have been validated as effective predictors of patient outcomes. But the relationship between pyroptosis and colorectal cancer remains unclear. This study has established a gene signature associated with pyroptosis to forecast the prognosis of CRC patients.
An analysis of 52 pyroptosis genes was conducted in both CRC and normal colorectal tissues, leading to the discovery of differentially expressed genes (DEGs). Core pyroptosis-related genes were identified using least absolute shrinkage and selection operator (LASSO) Cox regression to establish a prognostic risk score (PRS) for predicting CRC patient outcomes. The TCGA cohort was split into high-risk and low-risk groups based on the PRS, followed by Gene Ontology (GO) and KEGG pathway analyses. Additionally, differences in the enrichment scores of 16 immune cell types and the activity of 13 immune-related pathways were compared. The role of SPTBN5, a core pyroptosis-related gene, was validated through functional experiments on human colorectal adenocarcinoma cells (SW480).
40 differentially expressed genes were identified from 52 pyroptosis genes. A risk model was subsequently developed using 25 core pyroptosis-related genes identified through LASSO Cox regression analysis, and this model was validated in GEO cohorts. GO and KEGG pathway analyses showed that the DEGs are predominantly associated with mineral absorption, thyroid hormone synthesis, and pancreatic secretion. Functional experiments demonstrated that down-regulation of SPTBN5 expression through transfection led to significant decreases in the proliferation, migration, and clonogenicity of SW480 cells.
The PRS can identify high-risk CRC patient groups and predict patient prognosis. SPTBN5 may present a potential therapeutic target for CRC.
细胞焦亡是一种新出现的程序性细胞死亡类型。细胞焦亡的机制主要包括炎性小体激活的细胞焦亡和非炎性小体激活的细胞焦亡。多种利用细胞焦亡相关基因表达的预后评分系统已被证实是患者预后的有效预测指标。但细胞焦亡与结直肠癌之间的关系仍不清楚。本研究建立了一个与细胞焦亡相关的基因特征，以预测结直肠癌患者的预后。
对52个细胞焦亡基因在结直肠癌组织和正常结直肠组织中进行分析，发现差异表达基因（DEGs）。使用最小绝对收缩和选择算子（LASSO）Cox回归确定核心细胞焦亡相关基因，以建立预测结直肠癌患者预后的预后风险评分（PRS）。根据PRS将TCGA队列分为高风险组和低风险组，随后进行基因本体（GO）和KEGG通路分析。此外，比较了16种免疫细胞类型的富集分数和13条免疫相关通路的活性差异。通过对人结直肠腺癌细胞（SW480）进行功能实验，验证了核心细胞焦亡相关基因SPTBN5的作用。
从52个细胞焦亡基因中鉴定出40个差异表达基因。随后使用通过LASSO Cox回归分析确定的25个核心细胞焦亡相关基因建立了一个风险模型，并在GEO队列中进行了验证。GO和KEGG通路分析表明，DEGs主要与矿物质吸收、甲状腺激素合成和胰腺分泌相关。功能实验表明，通过转染下调SPTBN5表达可导致SW480细胞的增殖、迁移和克隆形成能力显著降低。
PRS可识别高风险结直肠癌患者群体并预测患者预后。SPTBN5可能是结直肠癌的一个潜在治疗靶点。
