A Cartography of Siglecs and Sialyltransferases in Gynecologic Malignancies: Is There a Road Towards a Sweet Future?

Abstract

Altered surface glycosylation is a key feature of cancers, including gynecologic malignancies. Hypersialylation, the overexpression of sialic acid, is known to promote tumor progression and to dampen antitumor responses by mechanisms that also involve sialic acid binding immunoglobulin-like lectins (Siglecs), inhibitory immune receptors. Here, we discuss the expression patterns of Siglecs and sialyltransferases (STs) in gynecologic cancers, including breast, ovarian, and uterine malignancies, based on evidence from The Cancer Genome Atlas. The balance between sialosides generated by specific STs within the tumor microenvironment and Siglecs on leukocytes may play a decisive role for antitumor immunity. An interdisciplinary effort is required to decipher the characteristics and biological impact of the altered tumor sialome in gynecologic cancers and to exploit this knowledge to the clinical benefit of patients.

Keywords: The Cancer Genome Atlas; cancer immunotherapy; gynecologic malignancies; sialic acid binding immunoglobulin-like lectins; sialyltransferases.

Figure 1

Tissue RNA expression of sialyltransferases (STs) in gynecologic cancers. RNA tissue expression of known human STs in breast carcinoma (BRCA; n = 1,094), ovarian serous cystadenocarcinoma (n = 305), uterine corpus endometrial carcinoma (n = 545), uterine carcinosarcoma (n = 57), and colon adenocarcinoma (COAD; n = 455), ranked upon expression in BRCA. Data are expressed as box-and-whisker diagrams (median, lower, and upper quartiles; horizontal lines define minimum and maximum). The results shown here are in whole or part based upon data generated by the The Cancer Genome Atlas Research Network: http://cancergenome.nih.gov/. Figures were created in R version 3.4.2. **p < 0.01, ***p < 0.001, one-way ANOVA followed by Bonferroni’s post-test.

Figure 2

Tissue RNA expression of sialic acid binding immunoglobulin-like lectins (Siglecs) in gynecologic cancers. RNA tissue expression of Siglecs in breast carcinoma, ovarian serous cystadenocarcinoma, uterine corpus endometrial carcinoma, uterine carcinosarcoma, and colonic adenocarcinoma, computed by a dendrogram clustering algorithm in R version 3.4.2. The results shown here are in whole or part based upon data generated by the The Cancer Genome Atlas Research Network: http://cancergenome.nih.gov/.