2. Academic Validation
  3. Transcriptomic landscape of transposable elements reveals LTR7- PLAAT4 as a potential oncogene and therapeutic target in pancreatic adenocarcinoma

Transcriptomic landscape of transposable elements reveals LTR7- PLAAT4 as a potential oncogene and therapeutic target in pancreatic adenocarcinoma

  • Genome Res. 2026 Feb 3;36(2):275-290. doi: 10.1101/gr.280528.125.
Meilong Shi # 1,  Chuanqi Teng # 1,  Shan Zhang # 2,  Xiaobo He # 3,  Lingyun Xu 4 5,  Fengxian Han 4 5,  Rongqi Wen 5,  Ganjun Yu 3,  Jingwen Liu 6,  Yang Feng 7,  Yanfeng Wu 8,  Yan Ren 9 10,  Gang Jin 11,  Jing Li 12 5 13
Affiliations

Affiliations

  • 1 Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Second Military Medical University (Naval Medical University), Shanghai 200433, China.
  • 2 Center for Translational Medicine, Second Military Medical University (Naval Medical University), Shanghai 200433, China.
  • 3 National Key Laboratory of Immunity and Inflammation, Institute of Immunology, Naval Medical University, Shanghai 200433, China.
  • 4 School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.
  • 5 Department of Precision Medicine, Changhai Hospital, Second Military Medical University (Naval Medical University), Shanghai 200433, China.
  • 6 Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
  • 7 College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
  • 8 National Key Laboratory of Immunity and Inflammation, Institute of Immunology, Naval Medical University, Shanghai 200433, China; [email protected] [email protected] [email protected] [email protected].
  • 9 Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; [email protected] [email protected] [email protected] [email protected].
  • 10 HIM-BGI Omics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang, Hangzhou 310022, China.
  • 11 Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Second Military Medical University (Naval Medical University), Shanghai 200433, China; [email protected] [email protected] [email protected] [email protected].
  • 12 School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China; [email protected] [email protected] [email protected] [email protected].
  • 13 State Key Laboratory for Macromolecule Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325030, China.
  • # Contributed equally.
PMID: 41506784 DOI: 10.1101/gr.280528.125
Abstract

Eukaryotic genomes contain numerous transposable elements (TEs), whose dysregulation threatens genome stability and may contribute to Cancer. Pancreatic adenocarcinoma (PAAD) is among the deadliest cancers, marked by abundant stroma that obscures tumor-specific molecular signals, complicating bulk-tissue analyses. Here, using 71 patient-derived PAAD organoids, we show that TE activities may potentially promote tumorigenesis and provide a source of novel immunotherapeutic targets. We identify 16 new TE-derived transcripts fused with 15 known oncogenes, exhibiting potential oncogenic function and prognostic value. Notably, LTR7-PLAAT4, present in 29% of tumors, encodes a protein variant transcriptionally regulated by FOXM1 binding to the LTR7 promoter. LTR7-PLAAT4 isoform 2 is associated with increased Cholesterol ester accumulation and lipid droplet formation mediated through BSCL2 coexpression, potentially fostering tumor progression. On the immunogenic front, HLA-I immunopeptidomics of AsPC-1 cells and DAC13 organoids identify over 11,000 peptides respectively. Althought mutation-derived neoantigens are rare, several peptides are originated from TE-chimeric transcripts, including four predicted by TEprof2. The peptide FLIQHLPLV, detected in 27% of organoids, exhibits robust immunogenicity, validated by T2 binding, mass spectrometry and ELISPOT assays with HLA-genotyped PBMCs. Together, these findings suggest that TE activities may contribute to PAAD progression and diversify its immunopeptidome, providing new opportunities for molecular subtyping and potential immunotherapeutic intervention.

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