Identification of AC025811.3 and AC012354.6 as two critical survival-related lncRNAs for uterine corpus cancer.

Abstract

Uterine corpus endometrial carcinoma (UCEC) ranks as the most frequently diagnosed gynecologic malignancy and the second leading cause of gynecologic cancer-related mortality. Long non-coding RNAs (lncRNAs) have emerged as critical regulators of gene expression and tumor biology; however, their prognostic significance in UCEC remains largely unexplored. To systematically identify survival-associated lncRNA biomarkers, we integrated clinical and transcriptomic data from two independent cohorts: TCGA-UCEC (548 tumor, 35 normal) and CPTAC-Uterus (102 tumor, 15 normal). Following upper quartile normalization and ComBat-based batch effect correction, differentially expressed lncRNAs (FDR < 0.01, |log2FC| > 2) were identified using Student's t-test. The intersecting set of consistently dysregulated lncRNAs from both cohorts was subjected to Cox proportional hazards regression to identify survival-associated candidates. Functional inference was performed through Spearman correlation with protein-coding genes and Gene Set Enrichment Analysis (GSEA) of KEGG pathways. A total of 550 lncRNAs were consistently downregulated and 148 were upregulated in UCEC across both cohorts. Cox regression identified 30 survival-associated lncRNAs (FDR < 0.01), all with elevated expression correlating with worse overall survival. The top two candidates, AC025811.3 and AC012354.6, showed significant stage-dependent expression patterns across FIGO stages I-IV and were functionally enriched in immune regulation and carbohydrate metabolism pathways. In conclusions, AC025811.3 and AC012354.6 represent novel candidate prognostic lncRNA biomarkers in UCEC. Experimental validation, including FISH-based tissue localization and staged quantification, and functional assays, is warranted to confirm their biological roles.