Integrative Analysis of the Expression of SIGLEC Family Members in Lung Adenocarcinoma via Data Mining

Abstract

Background: Sialic acid-binding immunoglobulin-type lectin (SIGLEC) family members are involved in regulating immune-cell activation, proliferation, and apoptosis, and they play an important role in tumor development. However, their expression and correlation with immune molecules in lung adenocarcinoma (LUAD) remain unclear.Methods: We utilized Gene Expression Profiling Interactive Analysis, Kaplan–Meier analysis, the limma package in R/Bioconductor, the University of California Santa Cruz Cancer Genome Browser, cBioPortal, STRING, Cytoscape, DAVID, and the Tumor Immune Estimation Resource for gene and protein profiling and analyses.Results: The results showed that SIGLEC10 and SIGLEC15 levels were upregulated in LUAD, whereas SIGLEC1, CD22 (SIGLEC2), CD33, myelin-associated glycoprotein (SIGLEC4), SIGLEC5, SIGLEC6, SIGLEC7, SIGLEC8, SIGLEC11, and SIGLEC14 levels were significantly downregulated, with their low expression associated with poor overall survival. Moreover, we observed high SIGLEC-mutation rates (22%) in LUAD patients, with SIGLEC functions determined as primarily involved in regulating the immune response, signal transduction, inflammatory response, and cell adhesion. Furthermore, we found that SIGLEC expression was significantly correlated with immune-cell infiltration, especially macrophages, neutrophils, and dendritic cells, and highly associated with immune molecules such as CD80, CD86, CD28, B-cell-activating factor, programmed cell death 1 ligand 2, and colony stimulating factor 1 receptor.Conclusion: These results provide insight into the potential molecular mechanism associated with SIGLEC-related development of LUAD, as well as clues for screening biomarkers and therapeutic targets.

Siglec-15 Regulates the Inflammatory Response and Polarization of Tumor-Associated Macrophages in Pancreatic Cancer by Inhibiting the cGAS-STING Signaling Pathway

“…In recent years, members of the sialic acid-binding immunoglobulin-like lectin (Siglecs) family are reported to play a critical role in regulation of immune tolerance, inflammatory response, and tumor progression of various tumors [21][22][23]. Among them, Sigelc-15 appears as an emerging target for tumor immunotherapy especially for patients who do not respond to PD-1/PD-L1 inhibitor treatment.…”

Forkhead box L2 is a target of miR‐133b and plays an important role in the pathogenesis of non‐small cell lung cancer

“…However, the exact mechanism remains to be fully elucidated, especially in lung cancer, which we focused on. Aberrant gene expression 55 and epigenetic modifications, have been proven to be involved in tumorigenesis. Moreover, the microenvironment in which cancer cells develop and survive is critical to tumor progression and treatment responese 56 .…”

Analysis of SIGLEC12 expression, immunomodulation and prognostic value in renal cancer using multiomic databases

“…In this analysis, we performed a search for mRNA expression and obtained data related to SIGLEC12 for ontology categories such as cellular component, biological process, molecular function, and KEGG pathway enrichment. The data sources used for this analysis are available at [ 32 , 33 ].…”