TNFRSF1B GENE VARIANTS ON SUSCEPTIBILITY, CLINICOPATHOLOGICAL ASPECTS AND PROGNOSIS OF PATIENTS WITH CUTANEOUS MELANOMA

Background: Regulatory T lymphocytes (Treg) modulate the destruction of abnormal cells through the binding of tumor necrosis factor (TNF) to tumor necrosis factor receptor 2 (TNFR2) on its surface. The TNFR2 is encoded by the TNFRSF1B polymorphic gene. Healthy individuals may be at distinct risks of CM and CM patients may have tumors of different behaviors. Objectives: This study aimed to evaluate the roles of TNFRSF1B c.587T>G, c.*188A>G, c.*215C>T, and c.*922C>T single nucleotide variants (SNVs) in risk, clinicopathological aspects, and survival of CM patients. Methods: Genotypes from 433 CM patients and 502 controls were identified by real-time polymerase chain reaction and gene expression was analyzed by quantitative PCR. Interaction between miR-96 and miR-1271 with 3′-UTR of TNFRSF1B gene was evaluated by luciferase reporter assay. Results: Individuals with c.587TT genotype and individuals aged less than 54 years and with c.587TT genotype were under 1.41- and 1.81-fold increased risks of developing MC, respectively. Patients with c.*922CT or TT genotype, c.587TG or GG + c.*922CT or TT genotype, and TATT haplotype had 2.09, 2.16, and 1.86 more chances of presenting tumor progression, and 2.38, 3.01, and 1.97 more chances of evolving to death due to CM, respectively. TNFRSF1B expression was higher in individuals with c.*922TT genotype than in individuals with c.*922CC genotype (2.57 arbitrary units (AUs) ± 0.96 standard deviation (SD) versus 1.95 AUs ± 1.22 SD; P = 0.01). MiR-1271 showed more efficient binding with TNFRSF1B 3′-UTR region encoded by the C allele than by T allele of c.*922C>T SNV (71 versus 107%; P = 0.02). Conclusion: The data present preliminary evidence that TNFRSF1B c.587T>G and c.*922C>T inherited abnormalities alter risk and clinical aspects of CM, and act as independent prognostic factors in CM. If validated in further epidemiological studies, our data can be used to select individuals at high-risk of CM, who should receive special attention in tumor prevention and early detection.