TY - JOUR
T1 - Exploring the molecular landscape of cancer of unknown primary
T2 - A comparative analysis with other metastatic cancers
AU - Andersen, Laura
AU - Christensen, Ditte S.
AU - Kjær, Asbjørn
AU - Knudsen, Michael
AU - Andersen, Andreas K.
AU - Laursen, Maria B.
AU - Ahrenfeldt, Johanne
AU - Laursen, Britt E.
AU - Birkbak, Nicolai J.
N1 - Publisher Copyright:
© 2024 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
PY - 2024/10
Y1 - 2024/10
N2 - 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.
AB - 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.
KW - cancer of unknown primary
KW - genomic profile
KW - immune response to cancer
KW - transcriptomic profile
UR - http://www.scopus.com/inward/record.url?scp=85193343554&partnerID=8YFLogxK
U2 - 10.1002/1878-0261.13664
DO - 10.1002/1878-0261.13664
M3 - Journal article
C2 - 38750007
AN - SCOPUS:85193343554
SN - 1574-7891
VL - 18
SP - 2393
EP - 2406
JO - Molecular Oncology
JF - Molecular Oncology
IS - 10
ER -