Pan-cancer analysis reveals context-dependent roles of LINE-1 ORF1p in immune regulation and copy number alterations.

ABSTRACT: L1 comprises 17% of the human genome, with 50-150 full-length sequences capable of retrotransposition. Although largely inactive in normal somatic tissues, tumorigenesis leads to L1 derepression and overexpression of its RNA binding chaperone protein, ORF1p. A potential cancer biomarker, ORF1p expression is a hallmark of multiple cancers and an early event in precursor lesions. Our study provides a comprehensive pan-cancer analysis of ORF1p using CPTAC proteogenomic data, revealing a dichotomous role in modulating immune responses. Integrated analyses and supervised learning models divide ORF1p-high tumors into two groups: (1) high ORF1p associates with immunosuppression, reduced interferon signaling and diminished immune cell infiltration (HNSCC and LSCC), and (2) ORF1p-high tumors associ

SUBMITTER: Kaparos EI 

PROVIDER: S-EPMC12621695 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature