ArticleFrontiers in oncology2026
Novel transcriptomic alterations in poorly differentiated endometrial carcinomas: evidence from South African women.
Article in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Poorly differentiated endometrial carcinoma in Black African women is under-characterized at the transcriptomic level, although it is known for aggressive subtypes. We conducted the first RNA-seq analysis of formalin-fixed, paraffin-embedded (FFPE) tumors from Black South African women to explore population-specific gene expression, alternative splicing, and novel isoforms. Methods: Seventy-six FFPE tumor samples passed RNA quality thresholds (DV200 ≥ 30%) and were sequenced on the PacBio Onso™ short-read platform. StringTie assembled transcripts and estimated transcripts per million (TPMs); differential expression was quantified by mean log Results: Cohort-level analysis (n = 76) revealed the coordinated activation of signaling and broad repression of transcriptional programs. We detected 17,990 dysregulated transcripts (4,483 upregulated and 13,507 downregulated; range -4.81 to +2.99). Prominent upregulated transcripts included GJA1 (+2.99), GRN (+2.60), ZC3H3 (+2.58), PCSK4 (+2.55), HSPB7 (+2.55), BICRA (+2.49), LINC02692 (+2.23), MKNK2 (+2.03), and RARA (+0.76). Strong downregulation was observed for MRPL15 (-4.81), ZSCAN23 (-4.46), NUF2 (-4.37), RTN1 (-4.33), EIF3I (-4.31), CDC73 (-3.36), MYC (-2.96), FRS2 (-2.90), and zinc-finger factors including ZNF569 (-3.36), ZNF573 (-2.92), ZNF793 (-2.33), and ZNF382 (-1.87). Reactome enrichment linked the upregulated set to MAPK family/GPCR signaling, while the downregulated categories were associated with gene expression (transcription), RNA polymerase II transcription, cell cycle, and metabolism. Alternative splicing was pervasive, with recurrent high-magnitude events at cancer-relevant loci including GJA1 (SE), NF2 (A3/A5), LIN37 (A5), ECT2 (A3/A5), BCL2L11 (A3), UQCRH (A5), CSE1L (A3), BROX (A3), and multiple ZNFs. StringTie identified previously unannotated isoforms at LINC02692 (+2.23), LINC01605 (-0.62), ZNF793 (-2.33), ZNF382 (-1.87), and retained-intron transcripts at RAD51 (+1.30), RPS24 (-0.97), and RPS3A (-0.62). Conclusions: Poorly differentiated endometrial carcinomas in Black South African women show a distinct MAPK-linked activation pattern, along with transcriptional repression and extensive splicing changes. Aligning with findings in African Americans, this cohort highlights the unique aspects of isoform-resolved splicing and zinc-finger repression, suggesting that translational control, retinoid signaling, and RNA processing may be targets for biomarkers and therapy.
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