Evidence Based on an Integrative Analysis of Multi-Omics Data on METTL7A as a Molecular Marker in Pan-Cancer

Our plain-English summary of Evidence Based on an Integrative Analysis of Multi-Omics Data on METTL7A as a Molecular Marker in Pan-Cancer, by Z. Liu, Y. Chen, T. Shen (Biomolecules, 2023).

The study

• Authors: Z. Liu, Y. Chen, T. Shen
• Journal: Biomolecules
• Published: 2023;13(2)
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Methyltransferase-like protein 7A (METTL7A), an RNA N6-methyladenosine (m6A) methyltransferase, has attracted much attention as it has been found to be closely associated with various types of tumorigenesis and progression. This study provides a comprehensive assessment of METTL7A from a pan-cancer perspective using multi-omics data. The gene ontology enrichment analysis of METTL7A-binding proteins revealed a close association with methylation and lipid metabolism. We then explored the expression of METTL7A in normal tissues, cell lines, different subtypes and cancers, and found that METTL7A was differentially expressed in various cancer species, tumor molecular subtypes and immune subtypes. Evaluation of the diagnostic and prognostic value of METTL7A in pan-cancer revealed that METTL7A had high accuracy in tumor prediction. Moreover, the low expression of METTL7A significantly correlated with the poor prognosis, including kidney renal clear cell carcinoma (KIRC), mesothelioma and sarcoma, indicating that METTL7A could be a potential biomarker for tumor diagnosis and prognosis. We focused on KIRC after pre-screening and analyzed its expression and prognostic value in various clinical subgroups. We found that METTL7A was significantly related to tumor stage, metastasis stage, pathologic stage, primary therapy outcome, histologic grade and gender, and that low METTL7A expression was associated with poorer outcomes. Finally, we analyzed the immune infiltration and co-expressed genes of METTL7A as well as the differentially expressed genes in the high and low expression groups. In conclusion, METTL7A is a better molecular marker for pan-cancer diagnosis and prognosis and has high potential as a diagnostic and prognostic biomarker for KIRC.

In plain English

This was a computer-based analysis of publicly available gene data; it did not study asbestos or any other exposure. The authors analyzed existing public data on expression of a gene called METTL7A in tumor and normal tissue, including 9807 tumor samples from The Cancer Genome Atlas, across many cancers, including mesothelioma. The article does not give the number of mesothelioma samples or say whether they were pleural or peritoneal. METTL7A expression was significantly lower than in normal tissue in 18 cancer types, not including mesothelioma. For mesothelioma, lower METTL7A expression was associated with worse overall survival (hazard ratio 0.34, 95% confidence interval 0.21 to 0.56), disease-specific survival (0.26, 0.13 to 0.48) and progression-free interval (0.27, 0.15 to 0.47); the article does not say which expression group was the reference. METTL7A expression was also associated with immune subtypes in 8 cancer types, including mesothelioma. Most detailed work concerned kidney renal clear cell carcinoma. The authors concluded that METTL7A is a marker with diagnostic and prognostic value across cancers, especially kidney renal clear cell carcinoma. They noted that the study lacked experimental validation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Bioinformatics (computer) analysis of public gene-expression and clinical databases across many cancer types; no laboratory experiments
• Who was studied: Tissue samples from public databases: 7568 normal samples from GTEx, and 727 tissue samples taken next to tumors plus 9807 tumor samples from TCGA. These covered many cancer types including mesothelioma; the number of mesothelioma samples is not reported. The kidney renal clear cell carcinoma analysis compared 269 low-expression and 270 high-expression patients.
• Exposure: No asbestos or other environmental exposure was studied. The factor examined was the expression level of the METTL7A gene in existing database data.
• Main results:
  • Compared with normal tissue (TCGA plus GTEx data), METTL7A expression was significantly lower in 18 cancer types; mesothelioma was not among the 18 listed
  • METTL7A expression was significantly associated with immune subtypes in 8 cancer types, including mesothelioma (MESO)
  • METTL7A expression showed high accuracy (AUC above 0.9) for distinguishing tumor from normal tissue in 12 cancer types; mesothelioma was not among them
  • Mesothelioma, overall survival: HR = 0.34 (95% CI 0.21 to 0.56, p less than 0.001). The authors reported that lower METTL7A expression predicted poor prognosis; the article does not state which expression group the HR uses as reference.
  • Mesothelioma, disease-specific survival: HR = 0.26 (95% CI 0.13 to 0.48, p less than 0.001); reference group not stated
  • Mesothelioma, progression-free interval: HR = 0.27 (95% CI 0.15 to 0.47, p less than 0.001); reference group not stated
  • Kidney renal clear cell carcinoma: lower METTL7A expression was correlated with worse overall survival (HR = 0.38, 95% CI 0.27 to 0.53, p less than 0.001); reference group not stated
• The authors' conclusion: The authors concluded that METTL7A is a molecular marker with diagnostic and prognostic value across cancers, especially kidney renal clear cell carcinoma
• Limitations the authors state:
  • The findings were not validated by laboratory experiments

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Carcinogenesis, Prognosis, Carcinoma, Mesothelioma, Sarcoma, Biomarker, Metastasis.

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