TMSB4Y restrains sphingomyelin synthesis via de novo purine synthesis to exert a tumor suppressor function in male esophageal squamous cell carcinoma.

Y chromosome genes play a vital role in sex difference of cancer. The dysregulation and functional implications of Y chromosome genes in esophageal squamous cell carcinoma (ESCC) remains elusive. Here, we analyze the Y chromosome gene signature and identify TMSB4Y as an emerging prognostic predictor in male ESCC.

Multimodal analysis of cfDNA methylomes for early detecting esophageal squamous cell carcinoma and precancerous lesions.

Detecting early-stage esophageal squamous cell carcinoma (ESCC) and precancerous lesions is critical for improving survival. Here, we conduct whole-genome bisulfite sequencing (WGBS) on 460 cfDNA samples from patients with non-metastatic ESCC or precancerous lesions and matched healthy controls. We develop an expanded multimodal analysis (EMMA) framework to simultaneously identify cfDNA methylation, copy number variants (CNVs), and fragmentation markers in cfDNA WGBS data.

The transcriptional landscape and diagnostic potential of long non-coding RNAs in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a deadly cancer with no clinically relevant biomarkers for early detection. Here, we comprehensively characterized the transcriptional landscape of long non-coding RNAs (lncRNAs) in paired tumor and normal tissue specimens from 93 ESCC patients, and identified six key malignancy-specific lncRNAs that were integrated into a Multi-LncRNA Malignancy Risk Probability model (MLMRPscore). The MLMRPscore performed robustly in distinguishing ESCC from normal controls in multiple in-house and external multicenter validation cohorts, including early-stage I/II cancer.