Background: Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are molecularly distinct histological subtypes. LAP2-Emerin-MAN1 (LEM) domain containing 1 (LEMD1), a cancer-testis antigen implicated in squamous malignancies, remains insufficiently characterized at the multi-omic level in ESCC. Objectives: To perform a reproducible multi-omics analysis of LEMD1 using The Cancer Genome Atlas (TCGA)-esophageal carcinoma (ESCA) data, integrating gene expression, copy-number alteration (CNA) status, chromosomal instability metrics, and ABSOLUTE-derived subclonal genome fraction, with a specific focus on ESCC. Methods: We integrated TCGA-ESCA ribonucleic acid (RNA)-seq expression, clinical annotations, and survival endpoints. Copy-number profiles were assessed using genomic identification of significant targets in cancer, version 2 (GISTIC2) gene-level calls, arm-level calls with aneuploidy score, Affymetrix genome wide human snp array 6.0 (SNP6) segmentation, and ABSOLUTE-derived purity/ploidy metrics. Differential expressions, non-parametric tests, Spearman correlation, and Kaplan-Meier analyses were applied. Results: LEMD1 expression was significantly elevated in ESCC compared with EAC (log₂FC=0.805, false discovery rate (FDR)=0.019). Gene-level CNA analysis revealed frequent LEMD1 gain/amplification in ESCC (51.0%), with lower deletion rates compared with EAC (p=0.023). LEMD1 CNA strongly correlated with 1q arm-level status (Spearman ρ=0.666, p=7.6×10⁻¹⁰), consistent with its chromosomal location at 1q32.1. Furthermore, LEMD1 CNA correlated with fraction genome gained (ρ=0.279, p=0.00596) and ABSOLUTE subclonal genome fraction (ρ=0.312, p=0.004104), indicating associations with chromosomal instability and intra-tumor heterogeneity. Conclusions: LEMD1 is a lineage-associated transcript elevated in ESCC and frequently gained as part of chromosome 1q alterations. LEMD1 CNA status tracks genome-wide gain burden and subclonal copy number variation (CNV) fraction, supporting its utility as a multi-omic indicator linked to chromosomal instability in ESCC.
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Wang, X. B., Wang, X. F., Karim, S. A., Kue, C. S. (2026) Association of LEMD1 Overexpression and Chromosome 1q Gain with Chromosomal Instability in Esophageal Squamous Cell Carcinoma: A TCGA Multi-omics Analysis. Journal of Disease and Public Health, 2(1), 35-40.
https://doi.org/10.71052/jdph/HDPG7774