Exploring the molecular landscape of cancer of unknown primary: A comparative analysis with other metastatic cancers

Laura Andersen, Ditte S. Christensen, Asbjørn Kjær, Michael Knudsen, Andreas K. Andersen, Maria B. Laursen, Johanne Ahrenfeldt, Britt E. Laursen*, Nicolai J. Birkbak*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Abstract

Cancer of unknown primary (CUP) tumors are biologically very heterogeneous, which complicates stratification of patients for treatment. Consequently, these patients face limited treatment options and a poor prognosis. With this study, we aim to expand on the current knowledge of CUP biology by analyzing two cohorts: a well-characterized cohort of 44 CUP patients, and 213 metastatic patients with known primary. These cohorts were treated at the same institution and characterized by identical molecular assessments. Through comparative analysis of genomic and transcriptomic data, we found that CUP tumors were characterized by high expression of immune-related genes and pathways compared to other metastatic tumors. Moreover, CUP tumors uniformly demonstrated high levels of tumor-infiltrating leukocytes and circulating T cells, indicating a strong immune response. Finally, the genetic landscape of CUP tumors resembled that of other metastatic cancers and demonstrated mutations in established cancer genes. In conclusion, CUP tumors possess a distinct immunophenotype that distinguishes them from other metastatic cancers. These results may suggest an immune response in CUP that facilitates metastatic tumor growth while limiting growth of the primary tumor.

Original languageEnglish
JournalMolecular Oncology
Volume18
Issue10
Pages (from-to)2393-2406
Number of pages14
ISSN1574-7891
DOIs
Publication statusPublished - Oct 2024

Keywords

  • cancer of unknown primary
  • genomic profile
  • immune response to cancer
  • transcriptomic profile

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