经过全癌分析和实验证实,m6A甲基转移酶KIAA1429被鉴定为一种潜在的诊断、预后和免疫治疗生物标志物。
Pan-cancer analysis and experimental validation revealed the m6A methyltransferase KIAA1429 as a potential biomarker for diagnosis, prognosis, and immunotherapy.
发表日期:2023 Aug 21
作者:
Chao Ma, Qiming Zheng, Yepeng Wang, Guoxiang Li, Mengmeng Zhao, Zhigang Sun
来源:
Cellular & Molecular Immunology
摘要:
KIAA1429,又被称为VIRMA(与病毒相似的m6A甲基转移酶相关),通过调节m6A甲基化水平,在肿瘤发生中起着至关重要的作用。以往的研究报道了KIAA1429在多种癌症中广泛过度表达,与不良预后相关。然而,KIAA1429在肿瘤进展中的确切作用及其对免疫应答的影响仍不清楚。使用来自癌症基因图谱(TCGA)和基因型-组织表达(GTEx)数据库的数据,对KIAA1429在癌症中的表达进行了差异分析。我们使用生物信息学方法评估了KIAA1429在肿瘤患者的诊断、预后和免疫治疗中的作用。此外,我们还分析了KIAA1429与DNA甲基化、免疫治疗之间的关联性。使用RT-qPCR方法研究了11种细胞系中KIAA1429 mRNA的表达水平。发现KIAA1429在28种癌症类型中过度表达,但在急性髓性白血病(LAML)和卵巢浆液性囊腺癌(OV)患者中其表达相对较低。此外,KIAA1429与多种癌症的晚期阶段呈正相关。Kaplan-Meier(KM)分析表明,KIAA1429表达增高的患者存活时间较短。此外,KIAA1429与DNA甲基化、肿瘤浸润免疫细胞(TIICs)和肿瘤微环境(TME)之间存在强烈关联。RT-qPCR结果表明,与配对正常细胞相比,肿瘤细胞中KIAA1429表达明显增高。总之,我们的研究说明KIAA1429表达与多种癌症的不良预后呈正相关。此外,KIAA1429可作为特定肿瘤类型的诊断因子和免疫应答的预测因子。
KIAA1429, also known as VIRMA (vir-like m6A methyltransferase associated), plays a crucial role in tumorigenesis by modulating the level of m6A methylation. Previous studies have reported the prevalent overexpression of KIAA1429 in multiple cancers, related to a poor prognosis. Nevertheless, the precise role of KIAA1429 in tumor progression and its impact on the immune response remains unclear.A differential analysis of KIAA1429 expression was performed across cancers using data from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. We evaluated the role of KIAA1429 in the diagnosis, prognosis, and immunotherapy of tumor patients using bioinformatics methods. In addition, we also analyzed the associations between KIAA1429 and DNA methylation, immunotherapy. RT-qPCR was used to study the expression levels of KIAA1429 mRNA in 11 cell lines.KIAA1429 is found to be overexpressed in 28 cancer types, but its expression is relatively low in patients with acute myeloid leukemia (LAML) and ovarian serous cystadenocarcinoma (OV). Moreover, KIAA1429 demonstrates a positive correlation with advanced stages of multiple cancers. Kaplan-Meier (KM) analysis suggested that patients with elevated KIAA1429 expression had shorter survival. Furthermore, KIAA1429 shows strong associations with DNA methylation, tumor-infiltrating immune cells (TIICs), and the tumor microenvironment (TME). RT-qPCR results indicated significantly higher expression of KIAA1429 in tumor cells compared to matched-normal cells.In summary, our work illustrates that KIAA1429 expression is positively connected with poor prognosis in multiple cancers. Moreover, KIAA1429 could serve as a diagnostic factor and a predictor of immune response for specific tumor types.