Khalili-Tanha Ghazaleh, Mohit Reza, Asadnia Alireza, Khazaei Majid, Dashtiahangar Mohammad, Maftooh Mina, Nassiri Mohammadreza, Hassanian Seyed Mahdi, Ghayour-Mobarhan Majid, Kiani Mohammad Ali, Ferns Gordon A, Batra Jyotsna, Nazari Elham, Avan Amir
Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
J Cell Commun Signal. 2023 Dec;17(4):1469-1485. doi: 10.1007/s12079-023-00779-2. Epub 2023 Jul 10.
Colorectal cancer (CRC) is the third most common cause of cancer-related deaths. The five-year relative survival rate for CRC is estimated to be approximately 90% for patients diagnosed with early stages and 14% for those diagnosed at an advanced stages of disease, respectively. Hence, the development of accurate prognostic markers is required. Bioinformatics enables the identification of dysregulated pathways and novel biomarkers. RNA expression profiling was performed in CRC patients from the TCGA database using a Machine Learning approach to identify differential expression genes (DEGs). Survival curves were assessed using Kaplan-Meier analysis to identify prognostic biomarkers. Furthermore, the molecular pathways, protein-protein interaction, the co-expression of DEGs, and the correlation between DEGs and clinical data have been evaluated. The diagnostic markers were then determined based on machine learning analysis. The results indicated that key upregulated genes are associated with the RNA processing and heterocycle metabolic process, including C10orf2, NOP2, DKC1, BYSL, RRP12, PUS7, MTHFD1L, and PPAT. Furthermore, the survival analysis identified NOP58, OSBPL3, DNAJC2, and ZMYND19 as prognostic markers. The combineROC curve analysis indicated that the combination of C10orf2 -PPAT- ZMYND19 can be considered as diagnostic markers with sensitivity, specificity, and AUC values of 0.98, 1.00, and 0.99, respectively. Eventually, ZMYND19 gene was validated in CRC patients. In conclusion, novel biomarkers of CRC have been identified that may be a promising strategy for early diagnosis, potential treatment, and better prognosis.
结直肠癌(CRC)是癌症相关死亡的第三大常见原因。据估计,早期诊断的CRC患者五年相对生存率约为90%,而疾病晚期诊断的患者五年相对生存率为14%。因此,需要开发准确的预后标志物。生物信息学能够识别失调的通路和新型生物标志物。使用机器学习方法对来自TCGA数据库的CRC患者进行RNA表达谱分析,以识别差异表达基因(DEG)。使用Kaplan-Meier分析评估生存曲线,以识别预后生物标志物。此外,还评估了分子通路、蛋白质-蛋白质相互作用、DEG的共表达以及DEG与临床数据之间的相关性。然后基于机器学习分析确定诊断标志物。结果表明,关键上调基因与RNA加工和杂环代谢过程相关,包括C10orf2、NOP2、DKC1、BYSL、RRP12、PUS7、MTHFD1L和PPAT。此外,生存分析确定NOP58、OSBPL3、DNAJC2和ZMYND19为预后标志物。联合ROC曲线分析表明,C10orf2 - PPAT - ZMYND19的组合可被视为诊断标志物,其敏感性、特异性和AUC值分别为0.98、1.00和0.99。最终,在CRC患者中验证了ZMYND19基因。总之,已鉴定出CRC的新型生物标志物,这可能是早期诊断、潜在治疗和更好预后的有前景的策略。