Yang Yang, Yang Xinyu, Ren Shiqi, Cao Yang, Wang Ziheng, Cheng Zhouyang
Department of Trauma Center, Affiliated Hospital of Nantong University, Medicial School of Nantong University, No.20 Xisi Road, Chongchuan District, 226001, Nantong City, Jiangsu Province, China.
Department of Emergency Medicine, Affiliated Hospital of Nantong University, No.20 Xisi Road, Chongchuan District, Nantong City, Jiangsu Province, 226001, China.
Heliyon. 2024 Mar 5;10(6):e27388. doi: 10.1016/j.heliyon.2024.e27388. eCollection 2024 Mar 30.
Colon adenocarcinoma (COAD) is a highly lethal gastrointestinal malignancy. The five-year survival rate of metastatic colorectal cancer remains low, at 14 percent. Numerous publications have suggested a role for peroxisome proliferator-activated receptors (PPARs) in malignancy. Recent studies have shown that PPARs, as nuclear transcription factors, may serve as potential targets for the treatment of metabolic syndrome tumors and their associated complications. However, the molecular mechanism has not been thoroughly investigated. Hence, in order to enhance the prediction of personalized medicine for PPAR-associated modulators in malignancy treatment, a timely review becomes essential. Utilizing TCGA-COAD expression profile data and patient overall survival (OS) information, this study systematically conducted investigations to identify and develop Hub stem cell-related diagnostic and prognostic identification models, aiming to enhance the multi-gene markers for COAD. Utilizing the differential expression profiles of stem cell-related genes, an 11-gene (SLC27A4, CPT1C, CPT1B, CPT2, CYP4A11, FABP3, FABP7, AQP7, MMP1, ACOX1, ANGPTL4) diagnostic and prognostic model was developed. This model demonstrated precise diagnostic and prognostic capabilities and holds the potential to characterize the clinicopathologic features of COAD. Univariate and multivariate Cox proportional hazards regression analyses were conducted to ascertain the independent factors influencing OS outcomes in COAD. The results revealed that CPT1B, SLC27A4, and FABP3 were identified as independent risk prognostic factors for OS in COAD, whereas ACOX1 and CPT2 served as independent protective prognostic factors. The hub genes associated with PPARs were identified through the differential expression of contrast agent COAD and normal tissues. Finally, the investigation of variations in immune infiltration and the analysis of relevant biological pathways validate the prognostic significance of the independent post-factors within this molecular model. This research aims to provide references for comprehending the mechanism of post-transcriptional regulation of COAD and molecular therapy.
结肠腺癌（COAD）是一种极具致死性的胃肠道恶性肿瘤。转移性结直肠癌的五年生存率仍然很低，仅为14%。众多出版物表明过氧化物酶体增殖物激活受体（PPARs）在恶性肿瘤中发挥作用。最近的研究表明，PPARs作为核转录因子，可能成为治疗代谢综合征肿瘤及其相关并发症的潜在靶点。然而，其分子机制尚未得到充分研究。因此，为了加强对PPAR相关调节剂在恶性肿瘤治疗中个性化医疗的预测，及时进行综述变得至关重要。本研究利用TCGA-COAD表达谱数据和患者总生存（OS）信息，系统地开展研究以识别和开发与枢纽干细胞相关的诊断和预后识别模型，旨在增强COAD的多基因标志物。利用干细胞相关基因的差异表达谱，开发了一个由11个基因（SLC27A4、CPT1C、CPT1B、CPT2、CYP4A11、FABP3、FABP7、AQP7、MMP1、ACOX1、ANGPTL4）组成的诊断和预后模型。该模型显示出精确的诊断和预后能力，并且有潜力描绘COAD的临床病理特征。进行单变量和多变量Cox比例风险回归分析，以确定影响COAD患者OS结局的独立因素。结果显示，CPT1B、SLC27A4和FABP3被确定为COAD患者OS的独立风险预后因素，而ACOX1和CPT2则是独立的保护性预后因素。通过对比剂COAD与正常组织的差异表达，确定了与PPARs相关的枢纽基因。最后，对免疫浸润变化的研究以及相关生物学途径的分析，验证了该分子模型中独立预后因素的预后意义。本研究旨在为理解COAD的转录后调控机制和分子治疗提供参考。
