用于预测接受新辅助放化疗的局部晚期直肠癌的治疗反应和预后的新型生物标志物。
Novel biomarkers to predict treatment response and prognosis in locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy.
发表日期:2023 Nov 12
作者:
Bingjie Guan, Meifang Xu, Rong Zheng, Guoxian Guan, Benhua Xu
来源:
GENES & DEVELOPMENT
摘要:
为了确定与接受新辅助放化疗 (NCRT) 的局部晚期直肠癌 (LARC) 患者的治疗反应和预后相关的基因。在我们的队列中,检查并生成了 NCRT 前 64 个肿瘤活检样本的基因表达谱。进行加权基因共表达网络分析来识别基因模块。外部验证数据集包括 GSE3493、GSE119409 和 GSE133057。使用免疫组织化学(IHC)评估候选基因的表达。 TIMER 用于评估免疫浸润。我们使用我们的数据和外部验证数据集确定并验证了预测 CCT5 和 ELF1 治疗反应的能力。 GSE133057 数据集中候选基因的生存差异趋势与我们的队列相似。高水平的 CCT5 和 ELF1 表达与 NCRT 耐药和不良预后相关。此外,还通过 IHC 方法评估了 117 例 LARC 患者样本中 CCT5 和 ELF1 的表达。基于 IHC 结果和 Cox 分析,构建了 CCT5 和 ELF1 的风险评分模型并表现良好。风险评分是 LARC 患者无进展生存期和总生存期的独立预后因素,然后用于构建列线图模型。使用基因集富集分析探讨了 CCT5 和 ELF1 的潜在机制。潜在的途径包括细胞凋亡、细胞周期和其他过程。 CCT5和ELF1表达与免疫细胞浸润显着相关。CCT5和ELF1被确定为LARC患者治疗反应和预后的生物标志物。风险评分模型和列线图有助于预测接受 NCRT 的 LARC 患者的治疗反应和生存结果。© 2023。作者。
To identify genes associated with treatment response and prognosis for locally advanced rectal cancer (LARC) patients receiving neoadjuvant chemoradiotherapy (NCRT).In our cohort, gene expression profiles of 64 tumor biopsy samples before NCRT were examined and generated. Weighted gene co-expression network analysis was performed to identify gene modules. External validation datasets included GSE3493, GSE119409, and GSE133057. The expression of candidate genes was evaluated using immunohistochemistry (IHC). TIMER was used to assess immune infiltration.We identified and validated the capability to predict the treatment response of CCT5 and ELF1 using our data and external validation datasets. The trends of survival differences of candidate genes in the GSE133057 dataset were similar to our cohort. High levels of CCT5 and ELF1 expression were associated with NCRT resistance and poor prognosis. Furthermore, the expression of CCT5 and ELF1 were also assessed in 117 LARC patients' samples by the IHC method. Based on IHC results and Cox analysis, the risk score model with CCT5 and ELF1 was constructed and performed well. The risk score was an independent prognostic factor for progression-free survival and overall survival in LARC patients and was then used to build nomogram models. The underlying mechanisms of CCT5 and ELF1 were explored using gene set enrichment analysis. The underlying pathway including apoptosis, cell cycle, and other processes. CCT5 and ELF1 expressions were significantly correlated with immune cell infiltration.CCT5 and ELF1 were determined as biomarkers for treatment response and prognosis in LARC patients. The risk score model and nomograms helped predict treatment response and survival outcomes for LARC patients undergoing NCRT.© 2023. The Author(s).