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PreprintCC BYbioRxiv

Multi-Omic and Spatial Profiling Defines Outcome-Associated Tumor States in Head and Neck Adenoid Cystic Carcinoma

  1. 1University of New Mexico

Abstract

Head and neck adenoid cystic carcinoma (HNACC) shows highly variable clinical behavior that histopathological features only partly predict, and prognostic biomarkers for aggressive disease at diagnosis remain limited. Here, we show by integrating bulk, single-cell, and spatial transcriptomes from 25 HNACC tumors that poor survival is marked by profound loss of myoepithelial tumor cells and expansion of luminal tumor states. Both outcome groups share a myoepithelial-like origin, but aggressive tumors converge on an actively dividing, MYC/E2F-driven luminal state concentrated in discrete spatial niches. Aggressiveness therefore reflects where tumors end along a shared developmental path rather than a distinct lineage or altered immune infiltration. A four-gene classifier capturing this state predicted survival in an independent cohort, outperforming larger signatures and flagging aggressive subgroups in two others. These findings define a lineage proliferation axis linked to HNACC outcome, providing a basis for prospective risk stratification and proliferative-directed therapy.

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BibTeX
@misc{bijukumar2026multiomic,
  title = {{Multi-Omic and Spatial Profiling Defines Outcome-Associated Tumor States in Head and Neck Adenoid Cystic Carcinoma}},
  author = {G. Bijukumar and K. J. Brayer and A. Vijayakumar and E. L. Bearer and D. Y. Lee and R. K. Orosco and S. Ness and J. S. Edwards and V. Palanisamy},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.07.757413},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.07.757413v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Multi-Omic and Spatial Profiling Defines Outcome-Associated Tumor States in Head and Neck Adenoid Cystic Carcinoma
AU  - G. Bijukumar
AU  - K. J. Brayer
AU  - A. Vijayakumar
AU  - E. L. Bearer
AU  - D. Y. Lee
AU  - R. K. Orosco
AU  - S. Ness
AU  - J. S. Edwards
AU  - V. Palanisamy
PY  - 2026
DA  - 2026/10/07
PB  - bioRxiv
DO  - 10.64898/2026.10.07.757413
UR  - https://www.biorxiv.org/content/10.64898/2026.10.07.757413v1
AB  - Head and neck adenoid cystic carcinoma (HNACC) shows highly variable clinical behavior that histopathological features only partly predict, and prognostic biomarkers for aggressive disease at diagnosis remain limited. Here, we show by integrating bulk, single-cell, and spatial transcriptomes from 25 HNACC tumors that poor survival is marked by profound loss of myoepithelial tumor cells and expansion of luminal tumor states. Both outcome groups share a myoepithelial-like origin, but aggressive tumors converge on an actively dividing, MYC/E2F-driven luminal state concentrated in discrete spatial niches. Aggressiveness therefore reflects where tumors end along a shared developmental path rather than a distinct lineage or altered immune infiltration. A four-gene classifier capturing this state predicted survival in an independent cohort, outperforming larger signatures and flagging aggressive subgroups in two others. These findings define a lineage proliferation axis linked to HNACC outcome, providing a basis for prospective risk stratification and proliferative-directed therapy.
ER  -