Cross cohort transcriptomic assessment of SIGLEC1 as a candidate marker of myeloid remodeling in recurrent glioblastoma

Background We assessed SIGLEC1 , encoding CD169, as a candidate marker of myeloid remodeling in recurrent glioblastoma. Methods Patient-level analyses combined discovery single-nucleus data, three paired tissue cohorts, GSE174554 and CARE nuclear data, and unpaired CGGA693/325 tissue comparisons. Original discovery labels were benchmarked; fixed-program, reference-gene and longitudinal sensitivities were assessed. Results Tissue SIGLEC1 increased in 9/11, 12/13 and 11/17 patients in the original paired cohorts (Benjamini–Hochberg [BH] q = 0.0122, 0.00407 and 0.0322). CGGA693 showed higher recurrent-tissue expression (108 primary, 79 recurrent; difference 0.745 log2[FPKM + 1], 95% CI 0.133–1.277; q = 0.000586). Reference-adjusted contrasts and CGGA325 did not replicate that association. Original discovery labels matched 62.4% of reconstructed nuclei, with clean-myeloid F1 = 0.967. Reconstructed discovery expression differed by 0.088 ln units (95% CI − 0.715 to 0.530; P = 0.855); original-label, GSE174554 and CARE recurrence tests were nonsignificant. CARE depth-adjusted interferon correlations were positive at both stages (median rho = 0.200/0.199; n = 51/54; q = 3.48 × 10 −9 /9.75 × 10 −10 ), consistent with GSE174554. Paired association changes did not establish recurrence specificity. Conclusions Tissue associations and replicated myeloid interferon correlations support a context-dependent candidate marker hypothesis. Consistent longitudinal induction and clinical biomarker performance remain unconfirmed.