Siglec-9, a cell surface transmembrane receptor mainly expressed on B cells, CD56+ NK cells, and CD4+ and CD8+ T cells, is strongly related to the
tumor immune microenvironment. However, the expression pattern of Siglec-9 and its prognostic potential have not been investigated in a pan-
cancer perspective. This study aimed to explore the association of Siglec-9 with prognosis,
tumor stage, molecular subtype, and the immune microenvironment in pan-
cancer. The
mRNA expression of Siglec-9 was obtained from The
Cancer Genome Atlas (TCGA), the Broad Institute
Cancer Cell Line Encyclopedia (CCLE), and Genotype-Tissue Expression (GTEx). The relationship between Siglec-9
mRNA expression and prognosis was evaluated by the Kaplan-Meier analysis. The correlation between Siglec-9 and
tumor-infiltrating immune cells, immune subtype, and molecular subtype was evaluated on
Tumor Immune Estimation Resource (TIMER) and Integrated Repository Portal for
Tumor-Immune System Interactions (TISIDB). The correlation between Siglec-9 expression and immune checkpoint, mismatch repair (MMR),
DNA methyltransferase (DNMT),
tumor mutation burden (TMB), and
microsatellite instability (MSI) was also analyzed. It showed that Siglec-9 expression was significantly altered in most TCGA
tumors. Siglec-9 expression was associated with the prognosis of patients with
adrenocortical carcinoma (ACC),
lung adenocarcinoma (LUSC),
thymoma (THYM),
colon adenocarcinoma (
COAD),
glioblastoma multiforme (GBM), prostate
adenocarcinoma (PRAD), esophageal
carcinoma (ESCA), and brain lower-grade
glioma (LGG). Particularly, increased Siglec-9 expression was strongly correlated with poor prognosis in LGG. Correlation between Siglec-9 expression and
tumor stage was also observed in various
cancers. In addition, Siglec-9 was positively associated with infiltration of immune cells including neutrophils, dendritic cells (DCs), macrophage, and CD4+ and CD8+ T cells. Moreover, a significant correlation between Siglec-9 and MSI, TMB, MMR, DNMT, immune checkpoint, immune subtype, molecular subtype, and
immunomodulators was observed in multiple
cancers. Specifically, poor prognostic value and strong correlation to immune cell infiltration were verified with the LGG dataset from the Chinese
Glioma Genome Atlas (CGGA). These findings indicated that Siglec-9 can be a novel
biomarker and a potential target for
cancer immunotherapy.