The prognostic significance of CXCR4 and SDF-1 in differentiated thyroid cancer depends on CD8+ density

Autor: Alexander Wilhelm, Isabelle Lemmenmeier, Alexandros Lalos, Alberto Posabella, Venkatesh Kancherla, Salvatore Piscuoglio, Tarik Delko, Markus von Flüe, Kathrin Glatz, Raoul André Droeser
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: BMC Endocrine Disorders, Vol 22, Iss 1, Pp 1-11 (2022)
Druh dokumentu: article
ISSN: 1472-6823
77144287
DOI: 10.1186/s12902-022-01204-2
Popis: Abstract Background Tumor infiltration with cytotoxic CD8+ T-cells is associated with a favorable outcome in several neoplasms, including thyroid cancer. The chemokine axis CXCR4/SDF-1 correlates with more aggressive tumors, but little is known concerning the prognostic relevance in relation to the tumor immune microenvironment of differentiated thyroid cancer (DTC). Methods A tissue microarray (TMA) of 37 tumor specimens of primary DTC was analyzed by immunohistochemistry (IHC) for the expression of CD8+, CXCR4, phosphorylated CXCR4 and SDF-1. A survival analysis was performed on a larger collective (n = 456) at RNA level using data from The Cancer Genome Atlas (TCGA) papillary thyroid cancer cohort. Results Among the 37 patients in the TMA-cohort, the density of CD8+ was higher in patients with less advanced primary tumors (median cells/TMA-punch: 12.5 (IQR: 6.5, 12.5) in T1–2 tumors vs. 5 (IQR: 3, 8) in T3–4 tumors, p = 0.05). In the TCGA-cohort, CXCR4 expression was higher in patients with cervical lymph node metastasis compared to N0 or Nx stage (CXCR4high/low 116/78 vs. 97/116 vs. 14/35, respectively, p = 0.001). Spearman’s correlation analysis of the TMA-cohort demonstrated that SDF-1 was significantly correlated with CXCR4 (r = 0.4, p = 0.01) and pCXCR4 (r = 0.5, p = 0.002). In the TCGA-cohort, density of CD8+ correlated with CXCR4 and SDF-1 expression (r = 0.58, p
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