Yan Haixia, Ou Qinling, Chang Yonglong, Liu Jinhui, Chen Linzi, Guo Duanyang, Zhang Sifang
Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
College of Integrated Traditional Chinese & Western Medicine, Hunan University of Traditional Chinese Medicine, Changsha, Hunan, 410208, China.
Heliyon. 2024 Jul 17;10(14):e34535. doi: 10.1016/j.heliyon.2024.e34535. eCollection 2024 Jul 30.
Drug resistance is the primary obstacle to advanced tumor therapy and the key risk factor for tumor recurrence and death. 5-Fluorouracil (5-FU) chemotherapy is the most common chemotherapy for individuals with colorectal cancer, despite numerous options.
The Gene Expression Omnibus database was utilized to extract expression profile data of HCT-8 human colorectal cancer wild-type cells and their 5-FU-induced drug resistance cell line. These data were used to identify 5-FU resistance-related differentially expressed genes (5FRRDEGs), which intersected with the colorectal adenocarcinoma (COAD) transcriptome data provided by the Cancer Genome Atlas Program database. A prognostic signature containing five 5FRRDEGs (, , , , and ) was established after conducting a Cox regression analysis. We conducted nomogram development, drug sensitivity analysis, tumor immune microenvironment analysis, and mutation analysis to assess the therapeutic value of the prognostic qualities.
We identified 166 5FRRDEGs in patients with COAD. Subsequently, we created a prognostic model consisting of five 5FRRDEGs using Cox regression analysis. The patients with COAD were divided into different risk groups by risk score; the high-risk group demonstrated a worse prognosis than the low-risk group.
In summary, the 5FRRDEG-based prognostic model is an effective tool for targeted therapy and chemotherapy in patients with COAD. It can accurately predict the survival prognosis of these patients as well as to provide the direction for exploring the resistance mechanism underlying COAD.
耐药性是晚期肿瘤治疗的主要障碍,也是肿瘤复发和死亡的关键危险因素。尽管有多种选择,但5-氟尿嘧啶(5-FU)化疗仍是结直肠癌患者最常用的化疗方法。
利用基因表达综合数据库提取HCT-8人结直肠癌野生型细胞及其5-FU诱导的耐药细胞系的表达谱数据。这些数据用于鉴定与5-FU耐药相关的差异表达基因(5FRRDEGs),并与癌症基因组图谱计划数据库提供的结肠腺癌(COAD)转录组数据进行交叉分析。在进行Cox回归分析后,建立了一个包含五个5FRRDEGs(, , , ,和 )的预后特征模型。我们进行了列线图开发、药物敏感性分析、肿瘤免疫微环境分析和突变分析,以评估预后特征的治疗价值。
我们在COAD患者中鉴定出166个5FRRDEGs。随后,我们使用Cox回归分析创建了一个由五个5FRRDEGs组成的预后模型。根据风险评分将COAD患者分为不同的风险组;高风险组的预后比低风险组更差。
总之,基于5FRRDEG的预后模型是COAD患者靶向治疗和化疗的有效工具。它可以准确预测这些患者的生存预后,并为探索COAD潜在的耐药机制提供方向。