HLA-G 3' untranslated region polymorphic sites associated with increased HLA-G production are more frequent in patients exhibiting differentiated thyroid tumours.

Abstract

HLA-G is a nonclassical class I histocompatibility molecule implicated on the immune escape mechanism of tumour cells. We evaluated the genetic diversity of HLA-G 3' untranslated region (3'UTR) and associated polymorphic sites with clinical presentation and with the magnitude of HLA-G thyroid expression. Polymorphic sites at 3'UTR (14bpINS/DEL, +3003C/T, +3010C/G, +3027A/C, +3035C/T, +3142C/G, +3187A/G, +3196C/G) were characterized by sequencing analyses in blood samples of 72 patients exhibiting papillary thyroid carcinoma (PTC), 22 follicular thyroid carcinomas (FTC), 19 follicular adenomas (FA), 21 colloid goitres and 156 healthy controls. Compared to goitre and/or controls, patients with PTC exhibited higher frequency of 14bpDEL (P = 0·030), +3010G (P = 0·034), +3010CG (P = 0·044), +3142CG (P = 0·040), +3035C (P = 0·050) and +3187GG (P = 0·032). Patients with FTC presented higher frequency of 14bpINS/DEL (P = 0·020). The UTR-5 haplotype was underrepresented in PTC (P = 0·050). The +3003TT was more frequent in patients with PTC older than 45 years (P = 0·030). Male patients had a higher frequency of +3196GG (P = 0·040). Tumour multicentricity was associated with UTR-2 (P = 0·030). The following associations were observed in PTC and FTC combined: i) tumour size <2 cm with 14bpINS/INS (P = 0·030); ii) multicentricity with +3035CC (P = 0·030) and +3196GG (P = 0·030); iii) decreased thyroid HLA-G expression with +3196C and +3196CC; and iv) moderate HLA-G thyroid staining with UTR-2. HLA-G 3'UTR polymorphisms associated with a greater magnitude of HLA-G production were associated with differentiated thyroid tumours and with variables implicated in poor prognosis. These findings corroborate the unfavourable role of HLA-G in thyroid cancer.