Hematology (Amsterdam, Netherlands) · 2026
CHAF1A identified as a candidate biomarker and potential therapeutic target in Burkitt lymphoma through integrated bioinformatics and histopathological analysis.
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Lin Wen-Yuan, Chen Bei-Li, Wu Zhi-Mei, Liu Feng, Du Wen-Fang
Аннотация
BACKGROUND: Burkitt lymphoma (BL) is a highly aggressive malignancy with limited effective treatments due to toxicity/resistance. Identifying and prioritizing candidate biomarkers and potential therapeutic targets from complex transcriptomic data, ahead of functional validation, remains a major unmet need.
METHODS: We integrated differential gene expression analysis across BL vs. control cohorts (Gene Expression Omnibus [GEO] datasets GSE43677/GSE12453) with Random Forest machine learning to prioritize candidates. Validated top genes via immunohistochemistry in an independent cohort (n = 10 BL, n = 10 reactive lymphoid hyperplasia [RLH] controls), followed by immune cell infiltration analysis.
RESULTS: This approach identified four candidate genes; only Chromatin Assembly Factor 1 Subunit A (CHAF1A) showed profound protein-level overexpression in BL tumors vs. RLH. In a single-dataset CIBERSORT analysis, CHAF1A expression showed exploratory correlational associations with several immune-cell fractions, most strongly a positive association with M0 macrophages; these in silico associations are hypothesis-generating and do not by themselves establish a mechanistic role in the tumor immune microenvironment.
CONCLUSION: CHAF1A is identified as a candidate biomarker associated with BL that, in exploratory single-dataset analysis, also correlates with immune-cell infiltration; these findings nominate it as a potential therapeutic target that warrants functional validation in future studies.
METHODS: We integrated differential gene expression analysis across BL vs. control cohorts (Gene Expression Omnibus [GEO] datasets GSE43677/GSE12453) with Random Forest machine learning to prioritize candidates. Validated top genes via immunohistochemistry in an independent cohort (n = 10 BL, n = 10 reactive lymphoid hyperplasia [RLH] controls), followed by immune cell infiltration analysis.
RESULTS: This approach identified four candidate genes; only Chromatin Assembly Factor 1 Subunit A (CHAF1A) showed profound protein-level overexpression in BL tumors vs. RLH. In a single-dataset CIBERSORT analysis, CHAF1A expression showed exploratory correlational associations with several immune-cell fractions, most strongly a positive association with M0 macrophages; these in silico associations are hypothesis-generating and do not by themselves establish a mechanistic role in the tumor immune microenvironment.
CONCLUSION: CHAF1A is identified as a candidate biomarker associated with BL that, in exploratory single-dataset analysis, also correlates with immune-cell infiltration; these findings nominate it as a potential therapeutic target that warrants functional validation in future studies.