Abstract
In recent times, RNA modifications have garnered increased attention due to their involvement in the onset and progression of tumors, with N6-methyladenosine (m6A) modification being the most prevalent form. YTHDF2 is an m6A reading protein that can modulate RNA stability, transcription, and translation. This study aimed to explore the role of YTHDF2 in small cell lung cancer (SCLC) by collecting 20 SCLC patients from our hospital (cohort 1) and 48 Chinese SCLC patients from the GEO database (cohort 2). We evaluated the prognostic value of YTHDF2 using Kaplan-Meier survival analysis, Log-rank test, and Cox regression analysis. Additionally, we employed Gene Set Enrichment Analysis (GSEA) to screen different signaling pathways. We also investigated the correlation between the expression of m6A-related genes and SCLC molecular subtype and tumor immune microenvironment (TIME). Furthermore, we utilized multiplex immunofluorescence (mIF) staining to validate the immune infiltration of SCLC patient tissue sections. Our study revealed that YTHDF2 is an independent prognostic factor, which high expression is associated with low overall survival rate in SCLC. Low expression of YTHDF2 in SCLC tumors may enhance the molecular subtype transition from neuroendocrine (NE) to non-neuroendocrine (non-NE) subtype. Low YTHDF2 expression was closely associated with high immune infiltration, immune checkpoints, and other immune-related molecular features. Additionally, mIF detection showed a correlation between the low expression of YTHDF2 and CD4 + T cells and CD8 + T cells. Taken together, YTHDF2 could serve as a potential prognostic biomarker negatively correlated with tumor immune infiltration in SCLC.
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Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
Change history
31 August 2023
A Correction to this paper has been published: https://doi.org/10.1007/s10735-023-10146-5
Abbreviations
- SCLC:
-
Small cell lung cancer
- OS:
-
Overall survival
- GSEA:
-
Gene set enrichment analysis
- m6A:
-
N6-Methyladenosine
- YTHDF2:
-
YTH domain family 2
- KEGG:
-
Kyoto Encyclopedia of Genes and Genomes
- MCPcounter:
-
Microenvironment Cell Populations counter
- ssGSEA:
-
single-sample GSEA
- HR:
-
Hazard ratio
- NK:
-
Natural killer
- CYT:
-
Levels of cytolytic activity.
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G Chen and DD Ren: contributed equally to this work. YH Wang and H Wang: collected clinical information and analyzed the data. G Chen and DD Ren: wrote the manuscript. S Yang and JH Zhang: made critical revisions to the manuscript. G Chen and DD Ren: designed the study. All authors read and approved the final manuscript.
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Chen, G., Ren, D., Wang, Y. et al. YTHDF2 negatively correlates with tumor immune infiltration in small cell lung cancer. J Mol Histol 54, 365–377 (2023). https://doi.org/10.1007/s10735-023-10129-6
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DOI: https://doi.org/10.1007/s10735-023-10129-6