Pan-cancer analysis of RNA 5-methylcytosine reader (ALYREF)

Our plain-English summary of Pan-cancer analysis of RNA 5-methylcytosine reader (ALYREF), by X. Ye, Z. Tuo, K. Chen, et al (Oncology Research, 2024).

The study

• Authors: X. Ye, Z. Tuo, K. Chen, R. Wu, J. Wang, Q. Yu, L. Ye, A. Miyamoto, K.H. Yoo, C. Zhang, W. Wei, D. Li, D. Feng
• Journal: Oncology Research
• Published: 2024;32(3):503-515
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The increasing interest in RNA modifications has significantly advanced epigenomic and epitranscriptomic technologies. This study focuses on the immuno-oncological impact of ALYREF in human cancer through a pan-cancer analysis, enhancing understanding of this gene's role in cancer. We observed differential ALYREF expression between tumor and normal samples, correlating strongly with prognosis in various cancers, particularly kidney renal papillary cell carcinoma (KIRP) and liver hepatocellular carcinoma (LIHC). ALYREF showed a negative correlation with most tumor-infiltrating cells in lung squamous cell carcinoma (LUSC) and lymphoid neoplasm diffuse large B-cell lymphoma (DLBC), while positive correlations were noted in LIHC, kidney chromophobe (KICH), mesothelioma (MESO), KIRP, pheochromocytoma and paraganglioma (PARD), and glioma (GBMLGG). Additionally, ALYREF expression was closely associated with tumor heterogeneity, stemness indices, and a high mutation rate in TP53 across these cancers. In conclusion, ALYREF may serve as an oncogenic biomarker in numerous cancers, meriting further research attention.

© 2024 Ye et al.

In plain English

This study used public cancer databases and laboratory cell experiments to examine a gene called ALYREF, which recognizes a chemical mark (5-methylcytosine) on RNA. It did not study asbestos or any other exposure. The authors analysed data from The Cancer Genome Atlas (TCGA) covering 38 cancer types. One of these was mesothelioma, labelled MESO; the article does not say whether this meant pleural or peritoneal mesothelioma. Compared with normal samples, ALYREF expression was higher in nineteen cancers and lower in two. Its expression was associated with survival measures in many cancers, mesothelioma among them. In kidney renal papillary cell carcinoma and liver hepatocellular carcinoma, the association was statistically significant for every survival measure. In mesothelioma, ALYREF expression correlated positively with tumor-infiltrating immune cells, especially dendritic cells, and with a stemness index (r = 0.31). TP53 was the most often mutated gene in the urinary tumors and liver cancer examined. In kidney and prostate cancer cell lines, reducing ALYREF significantly slowed cell growth. The authors concluded that ALYREF could serve as an oncogenic biomarker in many cancers and deserves more research attention.

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: Bioinformatic (database) pan-cancer analysis of public TCGA gene-expression and survival data, plus laboratory experiments on cancer cell lines
• Who was studied: TCGA tumor and normal samples covering 38 cancer types, including mesothelioma (MESO). Patient numbers per cancer are not given in the text. Laboratory work used renal and prostate cancer cell lines (786-O, ACHN, CAKI-2, PC3, DU145).
• Exposure: No asbestos or other fiber exposure was studied. The variable examined was ALYREF gene (mRNA) expression, and in the cell experiments its reduction by small interfering RNA.
• Main results:
  • Compared with normal samples, ALYREF expression was higher in nineteen cancers and lower in two.
  • ALYREF expression was associated with prognostic indices (overall, disease-specific, disease-free and progression-free survival) in numerous cancers, a list that included mesothelioma (MESO).
  • In kidney renal papillary cell carcinoma (KIRP) and liver hepatocellular carcinoma (LIHC), ALYREF's relationship with prognosis was statistically significant across all prognostic indices.
  • ALYREF correlated positively with tumor-infiltrating cells in LIHC, KICH, MESO, KIRP, PARD and GBMLGG. In mesothelioma, the correlation with dendritic cells was high.
  • In mesothelioma, ALYREF expression was significantly correlated with the RNA expression-based stemness index (RNAss), r = 0.31.
  • In the urinary tumors and LIHC analysed for mutations, TP53 was the most mutated gene. Mutation frequencies of several genes varied significantly between high- and low-ALYREF groups. Mesothelioma was not part of this mutation analysis.
  • ALYREF siRNAs significantly inhibited proliferation of the 786-O, ACHN, CAKI-2, PC3 and DU145 cell lines.
• The authors' conclusion: The authors concluded that ALYREF could serve as an oncogenic biomarker in many cancer patients and should be given more attention by researchers.

Topics

Medical terms in this study, explained in our Lexicon: Prognosis, Carcinoma, Squamous Cell Carcinoma, Neoplasm, Mesothelioma, Biomarker.

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