Research Paper Volume 15, Issue 17 pp 8664—8691
Pan-cancer analysis and experimental validation revealed the m6A methyltransferase KIAA1429 as a potential biomarker for diagnosis, prognosis, and immunotherapy
- 1 Department of Thoracic Surgery, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong, China
- 2 School of Clinical Medicine, Weifang Medical University, Weifang 261053, Shandong, China
- 3 Jinan Central Hospital, Shandong University, Jinan 250013, Shandong, China
- 4 Research Center of Translational Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong, China
Received: February 1, 2023 Accepted: July 19, 2023 Published: August 21, 2023
https://doi.org/10.18632/aging.204968How to Cite
Copyright: © 2023 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Abbreviations
ACC: Adrenocortical carcinoma; AUC: Area under the curve; BLCA: Bladder urothelial carcinoma; BRCA: Breast invasive carcinoma; CHOL: Cholangiocarcinoma; COAD: Colon adenocarcinoma; DFI: Disease-free interval; DLBC: Lymphoid neoplasm diffuse large B-cell lymphoma; DSS: Disease-specific survival; ESCA: Esophageal carcinoma; ESCC: Esophageal squamous cell carcinoma; GBM: Glioblastoma multiforme; HNSC: Head and neck squamous cell carcinoma; ICIs: Immune checkpoint inhibitors; IHC: Immunohistochemistry; KIAA1429: Vir-Like m6A methyltransferase associated; KICH: Kidney chromophobe; KIRC: Kidney renal clear cell carcinoma; KIRP: Kidney renal papillary cell carcinoma; KM: Kaplan-Meier; LAML: Acute myeloid Leukemia; LGG: Brain lower grade glioma; LIHC: Liver hepatocellular carcinoma; LUAD: Lung adenocarcinoma; LUSC: Lung squamous cell carcinoma; MESO: Mesothelioma; MSI: Microsatellite instability; OS: Overall survival; OV: Ovarian serous cystadenocarcinoma; PAAD: Pancreatic adenocarcinoma; PCPG: Pheochromocytoma and paraganglioma; PFI: Progress-free interval; PRAD: Prostate adenocarcinoma; READ: Rectum adenocarcinoma; ROC: Receiver operating characteristic curve; RT-qPCR: Real-time quantitative polymerase chain reaction; SKCM: Skin cutaneous melanoma; STAD: Stomach adenocarcinoma; TGCT: Testicular germ cell tumors; THCA: Thyroid carcinoma; THYM: Thymoma; TIICs: Tumor-infiltrating immune cells; TMB: Tumor mutational burden; TME: Tumor microenvironment; Treg: Regulatory T cells; UCEC: Uterine corpus endometrial carcinoma; UCS: Uterine carcinosarcoma; UVM: Uveal melanoma.