Dataset Information

Dysregulated m6A-Related Regulators Are Associated With Tumor Metastasis and Poor Prognosis in Osteosarcoma.

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.

SUBMITTER: Li J

PROVIDER: S-EPMC7280491 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Dysregulated m6A-Related Regulators Are Associated With Tumor Metastasis and Poor Prognosis in Osteosarcoma.

Li Jianhao J Rao Benchen B Yang Jie J Liu Liwen L Huang Maoxin M Liu Xin X Cui Guangying G Li Chao C Han Qicai Q Yang Hao H Cui Xichun X Sun Ranran R

Frontiers in oncology 20200602

<b>Background:</b> 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. <b>Materials and Methods:</b> Public genome datasets a ...[more]

PMID: 32582536

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Project description:Hepatectomy generally offers the best chance of long-term survival for patients with hepatocellular carcinoma (HCC). Many studies have shown that hepatectomy accelerates tumor metastasis, but the mechanism remains unclear. In this study, palliative hepatectomy was performed in an orthotopic nude mice model of HCC (MHCC97H) with high metastatic potential. Using Human Tumor Metastasis Microarray, we screened the metastasis-related genes in tumor tissues following palliative resection, and found that Metastasis suppressor 1 (MTSS1) located in the central position of gene function net of residual HCC; MTSS1 was up-regulated in residual tumor after palliative resection. Further studies found that MTSS1 enhanced the metastasis of residual HCC. In hepatitis B-related HCC patients undergone palliative hepatectomy, those with higher MTSS1 mRNA expression accompanied by the activation of matrix metalloproteinase 2 (MMP2) in residual HCC, had earlier residual HCC detection after hepatectomy and poorer survival when compared to those with lower MTSS1 level. In different cell lines, the levels of MTSS1 mRNA increased in parallel with metastatic potential. MTSS1 down regulation via siRNA decreased MMP2 activity, reduced invasive potentials of HCC by 28.9% in vitro, and averted the deteriorated lung metastatic extent in vivo. In conclusion, the poor prognosis of hepatitis B-related HCC patients following palliative hepatectomy associates with elevated MTSS1 mRNA expression; therefore, MTSS1 may provide a new research field for HCC diagnosis and treatment. Eighteen nude mice bearing HCC xenografts were randomized into three groups 14 days after orthotopic implantation: palliative resection group (mice received partial HCC resection with preservation of 2 mm tumor pedicles), sham operation group (mice only undergone an exposure of liver but without resection), and blank control group (mice without further surgical intervention). All mice were sacrificed by cervical dislocation 14 days following palliative resection based on pre-experimental results. The first time surgically removed HCC tissues were named tumor tissues T1; the second time surgically removed HCC tissues from sham operation group were named tumor tissues T2; Tissues from blank control group were named tumor tissues T3; Tissues from palliative resection group were named tumor tissues T4 that was residual HCC. Randomly selected 5 tumor specimens from each group were used for the screen of genes related to metastasis by microarray techniques.

Project description:PurposeN6-methyladenosine (m6A) modifications represent one of the most common methylation modifications, and they are mediated by m6A RNA methylation regulators. However, their functions in renal cell carcinoma (RCC) are not completely understood. The aim of this study was to investigate the effects of the regulators in RCC.Materials and methodsThe expression levels of the 13 main m6A RNA methylation regulators in RCC were detected and consensus clustering was performed to explore their relationships with RCC. Thereafter, a risk signature based on the regulators was established. This risk model was fully verified by conducting prognostic analyses using two datasets (The Cancer Genome Atlas [TCGA] and Gene Expression Omnibus [GEO] datasets) and a ROC curve analysis.ResultsOf the 13 main m6A regulators, six were significantly upregulated and four were significantly downregulated in 893 RCC cases compared to 128 normal controls in the TCGA database. Consensus clustering based on the regulators identified two clusters of RCC cases, which were significantly associated with a pathological characteristic (T status). Thus, these results indicated that m6A RNA methylation regulators were associated with RCC. Thereafter, a risk model involving two of the regulators (METTL14 and WTAP) was established. The alterations in the mRNA and protein expression levels of these two regulators were further confirmed based on Human Protein Atlas data and real-time PCR in RCC and normal cell lines. The results indicated that the risk model may serve as an independent prognostic marker of overall survival, and it was also associated with clinicopathological characteristics (T status, M status, pathological stage, and gender) in RCC.ConclusionCollectively, the results of this study indicated that the risk model (based on two m6A RNA methylation regulators) may serve as an independent prognostic indicator of RCC, which may aid further investigation into m6A RNA modification in RCC.

Dataset Information

Dysregulated m6A-Related Regulators Are Associated With Tumor Metastasis and Poor Prognosis in Osteosarcoma.

Publications

Dysregulated m6A-Related Regulators Are Associated With Tumor Metastasis and Poor Prognosis in Osteosarcoma.

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