Guo Lei, Huai Qilin, Zhou Bolun, Ying Jianming, Guo Wei
Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing The People's Republic of China.
Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing The People's Republic of China.
Cancer Innov. 2022 Dec 16;1(4):328-343. doi: 10.1002/cai2.40. eCollection 2022 Dec.
Lung adenocarcinoma (LUAD) is the most common lung cancer worldwide. N6-methyladenosine (m6A) methylation is a messenger RNA (mRNA) modification that plays a key role in tumor growth, immune microenvironment, and immunotherapy response. This study investigated the expression level, mutation status, prognostic value, and predictive ability for response to anti-PD-1 immunotherapy of the m6A methyltransferase KIAA1429 in LUAD.
This study examined multiple public data cohorts and independent samples from National Cancer Center (NCC) to evaluate the clinical significance and prognostic value of KIAA1429 in LUAD using bioinformatics techniques and immunohistochemical staining. We also evaluated the predictive value of KIAA1429 expression for anti-PD-1 immunotherapy efficacy. GSEA analysis was performed using KIAA1429 RNA-seq data at the tumor tissue level and cellular level to explore the potential molecular mechanism.
In public databases, KIAA1429 was significantly associated with clinicopathological parameters in LUAD patients and had the potential to predict patient prognosis. The mutation characteristics of KIAA1429-related genes were analyzed and TP53, TTN, CSMD3, and other genes showed high mutation frequencies in LUAD. An independent cohort of 415 samples confirmed that high KIAA1429 expression was significantly associated with poorer prognosis in LUAD patients. Analysis of a small immunotherapy cohort showed that patients with high expression of KIAA1429 had better response after immunotherapy, and the proportion of patients with immunotherapy response was higher in this group.
Our study confirmed that KIAA1429 was highly expressed in LUAD and was significantly associated with poor prognosis. Moreover, KIAA1429 may serve as a potential marker to predict the efficacy of immunotherapy in LUAD.
肺腺癌（LUAD）是全球最常见的肺癌。N6-甲基腺苷（m6A）甲基化是一种信使核糖核酸（mRNA）修饰，在肿瘤生长、免疫微环境和免疫治疗反应中起关键作用。本研究调查了m6A甲基转移酶KIAA1429在LUAD中的表达水平、突变状态、预后价值以及对抗程序性死亡蛋白1（PD-1）免疫治疗反应的预测能力。
本研究检查了多个公共数据队列以及来自国家癌症中心（NCC）的独立样本，采用生物信息学技术和免疫组织化学染色评估KIAA1429在LUAD中的临床意义和预后价值。我们还评估了KIAA1429表达对抗PD-1免疫治疗疗效的预测价值。使用肿瘤组织水平和细胞水平的KIAA1429 RNA测序数据进行基因集富集分析（GSEA），以探索潜在的分子机制。
在公共数据库中，KIAA1429与LUAD患者的临床病理参数显著相关，并有预测患者预后的潜力。分析了KIAA1429相关基因的突变特征，发现TP53、TTN、CSMD3等基因在LUAD中具有较高的突变频率。一个由415个样本组成的独立队列证实，KIAA1429高表达与LUAD患者较差的预后显著相关。对一个小型免疫治疗队列的分析表明，KIAA1429高表达的患者在免疫治疗后反应较好，该组中免疫治疗有反应的患者比例更高。
我们的研究证实，KIAA1429在LUAD中高表达，且与不良预后显著相关。此外，KIAA1429可能作为预测LUAD免疫治疗疗效的潜在标志物。
