Abstract
BackgroundSIGLEC family genes can also be expressed on tumor cells in different cancer types, and though it has been found that SIGLEC genes expressed by immune cells can be exploited by tumors to escape immune surveillance, functions of tumor derived SIGLEC expression in tumor microenvironment (TME) were barely investigated, which could play roles in cancer patients’ survival.MethodsUsing bioinformatic analysis, mutation status of SIGLEC family genes was explored through the cBioPortal database, and expression of them in different tumors was explored through the UALCAN database. The GEPIA database was used to compare SIGLEC family genes’ mRNA between cancers and to generate a highly correlated gene list in tumors. A KM-plotter database was used to find the association between SIGLEC genes and survival of patients. The associations between SIGLEC family genes’ expression, immune infiltration, and immune regulators’ expression in TME were generated and examined by the TIMER 2.0 database; the differential fold changes of SIGLEC family genes in specific oncogenic mutation groups of different cancer types were also yielded by TIMER 2.0. The networks of SIGLEC family genes and highly correlated genes were constructed by the STRING database, and gene ontology and pathway annotation of SIGLEC family highly correlated genes were performed through the DAVID database.ResultsSIGLEC family genes were highly mutated and amplified in melanoma, endometrial carcinoma, non-small cell lung cancer, bladder urothelial carcinoma, and esophagogastric adenocarcinoma, while deep deletion of SIGLEC family genes was common in diffuse glioma. Alteration of SIGLEC family genes demonstrated different levels in specific tumors, and oncogenic mutation in different cancer types could influence SIGLEC family genes’ expression. Most SIGLEC family genes were related to patients’ overall survival and progression free survival. Also, tumor derived SIGLEC family genes were related to tumor immune cell infiltration and may regulate TME by influencing chemokine axis.ConclusionOur computational analysis showed SIGLEC family genes expressed by tumor cells were associated with tumor behaviors, and they may also influence TME through chemokine axis, playing vital roles in patients’ survival. Further experiments targeting tumor derived SIGLEC family genes are needed to confirm their influences on tumor growth, metastasis, and immune environment regulation.
Highlights
SIGLEC family genes translate a group of proteins belonging to the immunoglobulin superfamily in mammal animals, and they can be divided into conservative (SIGLEC1, SIGLEC2, SIGLEC4, and SIGLEC15) and highly evolved (SIGLEC3, SIGLEC5, SIGLEC6, SIGLEC7, SIGLEC8, SIGLEC9, SIGLEC10, SIGLEC11, SIGLEC14, and SIGLEC16) teams, which are widely expressed on immune cell populations’ membrane, mainly involving endocytosis and immune regulation in various diseases [1,2,3,4,5]
In diffuse glioma, deep deletion of SIGLEC family genes was common in comparison to 32 other types of tumor, and SIGLEC15 seemed to be deeply deleted in various tumors, while SIGLEC16 was amplified in mutating cancer types (Figure 2)
We found mRNA expression levels of SIGLEC family genes were different between normal and tumors tissues, and extremely in breast invasive carcinoma (BRCA), colon adenocarcinoma (COAD), head and neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), thyroid carcinoma (THCA), stomach adenocarcinoma (STAD), and uterine Corpus Endometrial Carcinoma (UCEC), almost all expressional difference of SIGLEC family genes achieved significance
Summary
SIGLEC family genes translate a group of proteins belonging to the immunoglobulin superfamily in mammal animals, and they can be divided into conservative (SIGLEC1, SIGLEC2, SIGLEC4, and SIGLEC15) and highly evolved (SIGLEC3, SIGLEC5, SIGLEC6, SIGLEC7, SIGLEC8, SIGLEC9, SIGLEC10, SIGLEC11, SIGLEC14, and SIGLEC16) teams, which are widely expressed on immune cell populations’ membrane, mainly involving endocytosis and immune regulation in various diseases [1,2,3,4,5]. SIGLEC family genes can be expressed by tumor cells across cancer types, and recently, studies have found SIGLEC15 expressed by tumor cells or macrophages in mouse melanoma model could directly depress CD8+ T cell infiltration and function in tumor microenvironment through binding to presumptive target on CD8+ T cells [13,14,15]. The explicit roles of tumor intrinsic SIGLEC family genes’ expression on patients’ survival, disease progression, and immune regulation in tumor microenvironment were still unknown, and we used bioinformatic analysis to find whether tumor derived expression of SIGLEC family genes played roles in those aspects, which could provide new thoughts for cancer immune therapy. SIGLEC family genes can be expressed on tumor cells in different cancer types, and though it has been found that SIGLEC genes expressed by immune cells can be exploited by tumors to escape immune surveillance, functions of tumor derived SIGLEC expression in tumor microenvironment (TME) were barely investigated, which could play roles in cancer patients’ survival
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