The expression of two immunosuppressive SIGLEC family molecules in papillary thyroid cancer and their effect on prognosis.

[BACKGROUND] The thyroid cancer (THCA) subtype that occurs more frequently is papillary thyroid cancer (PTC). Despite a favorable postoperative outcome, traditional antitumor therapy does not offer ideal results for patients with metastasis, relapse, and radioiodine resistance. Recent studies demonstrated the remarkable effects of immune checkpoint inhibitors on solid tumors, of which the immunoglobulin superfamily member SIGLEC10 and SIGLEC15 act as novel immunotherapy targets for tumors. Nevertheless, their role in PTC prognosis is still indefinite.

[METHODS] Immunohistochemistry was utilized to examine the expression of SIGLEC10 and SIGLEC15 in 244 PTC tissue specimens. Then the expression correlation between the two was analyzed in normal tissues (NT), tumor cells (TC), and tumor stroma (TS), respectively. Subsequently, the retrospective data on patients with PTC were collected to examine whether the two immunosuppressive SIGLEC family members could affect their prognosis.

[RESULTS] We confirmed that TC expressed higher levels of SIGLEC10 than NT. However, SIGLEC10 was down-regulated in TS and predicted poor outcomes. Meanwhile, down-regulation of SIGLEC15 expression was observed in both TC and TS, indicating a favorable prognosis. PTC patients with both SIGLEC10-SIGLEC15+ expression in TC and TS had a significantly higher recurrence risk. The expression of SIGLEC10 in TS and SIGLEC15 in TC or TS was an independent predictor of PFS, and a positive correlation was shown between SIGLEC10 and SIGLEC15 expression in TS.

[CONCLUSIONS] Therefore, our results indicate that SIGLEC10 and SIGLEC15 may be applied as significant prognostic markers for PTC and attractive targets for THCA immunotherapy.