Abstract
Background: Osteosarcoma (OS) is the most common primary bone tumor. The disease has a poor prognosis due to the delay in the diagnosis and the development of metastasis. N6-Methyladenosine (m6A)-related regulators play an essential role in various tumors. In this study, a comprehensive analysis was conducted to elucidate the relationship between the expression profiles of m6A-related molecules and the clinical outcome of OS patients.Materials and Methods: Public genome datasets and a tissue microarray (TMA) cohort were used to analyze the mRNA and protein expression levels of m6A regulators. Next, immunofluorescence (IF) analysis was used to determine the subcellular localization of m6A-related molecules. Kaplan–Meier and Cox regression analyses were performed to confirm the prognostic value of m6A-related molecules in OS. A comprehensive bioinformatic analysis was conducted to identify the potential molecular mechanisms mediated by m6A modification in OS.Results: We found that m6A-related regulator expression was dysregulated in OS tissues, especially in metastatic tumor tissues. Low expression of METTL3, METTL14, and YTHDF2 and high expression of KIAA1429 and HNRNPA2B1 were significantly associated with poor prognosis in the TMA cohort. Simultaneously, the genome meta-cohort analysis revealed that low expression of FTO and METTL14 and high expression of METTL3, HNRNPA2B1, and YTHDF3 were associated with poor prognosis in OS. Cox regression analysis showed that HNRNPA2B1 might be an independent risk factor for OS. Bioinformatic analysis indicated that m6A regulators might be involved in OS progression through humoral immune response and cell cycle pathways.Conclusion: M6A-related regulators are frequently dysregulated and correlate with metastasis and prognosis in OS. M6A-related regulators may serve as novel therapeutic targets and prognostic biomarkers for OS.
Highlights
Human osteosarcoma (OS) is one of the most common aggressive bone cancers, and it has higher incidence and mortality rates in teenagers; it frequently affects distal femur, proximal tibia, and humerus [1, 2]
Low expression of METTL3, METTL14, and YTHDF2 and high expression of KIAA1429 and HNRNPA2B1 were significantly associated with poor prognosis in the tissue microarray (TMA) cohort
The genome metacohort analysis revealed that low expression of FTO and METTL14 and high expression of METTL3, HNRNPA2B1, and YTHDF3 were associated with poor prognosis in OS
Summary
Human osteosarcoma (OS) is one of the most common aggressive bone cancers, and it has higher incidence and mortality rates in teenagers; it frequently affects distal femur, proximal tibia, and humerus [1, 2]. Despite significant progress in therapeutic strategies against OS over the past few decades, its prognosis remains poor due to the delay in the diagnosis and the development of metastasis [3]. M6A-related regulators are involved in various physiological and pathological processes through the regulation of RNA stability, mRNA splicing and translation, and microRNA processing [7,8,9]. The clinical value and potential mechanism of m6A-related regulators in OS are still unclear. Osteosarcoma (OS) is the most common primary bone tumor. N6-Methyladenosine (m6A)-related regulators play an essential role in various tumors. A comprehensive analysis was conducted to elucidate the relationship between the expression profiles of m6A-related molecules and the clinical outcome of OS patients
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