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Influence of IL1B (rs16944) and IL1R2 (rs4141134) polymorphisms on aggressiveness and prognosis of cutaneous melanoma.
Melanoma Research ( IF 2.2 ) Pub Date : 2021-07-19 , DOI: 10.1097/cmr.0000000000000763
Caroline Torricelli 1 , Juliana Carron 1 , Bruna Fernandes Carvalho 1 , Ligia Traldi Macedo 1, 2 , José Augusto Rinck-Junior 3 , Carmen Silvia Passos Lima 1, 2 , Gustavo Jacob Lourenço 1
Affiliation  

Cutaneous melanoma is the most aggressive skin cancer with high mortality. Proinflammatory cytokines can modulate the proliferation and survival of cutaneous melanoma cells. Higher levels of interleukin-1β (IL1B) were associated with tumor cell proliferation, invasion, and migration, and the IL-1 type II receptor (IL1R2) serves as an endogenous inhibitor of IL1B signaling. Single-nucleotide variations (SNVs) in these genes (IL1B rs16944 and IL1R2 rs4141134) can modulate cytokine production and binding; however, their role in cutaneous melanoma is still unknown. Thus, we investigated the influence of the above SNVs in clinicopathological aspects and cutaneous melanoma patients' survival. In the present study, we analyzed 193 patients with cutaneous melanoma for IL1B c.-598T>C (rs16944) and IL1R2 c.-2009G>A (rs4141134) genotypes with TaqMan assays. Differences between groups were calculated using χ2 or Fisher's exact test and multiple logistic regression. Progression-free survival (PFS) and melanoma-specific survival were calculated by Kaplan-Meier and Cox methods. The prognostic value of IL1R2 was also analyzed by the online consensus survival webserver for skin cutaneous melanoma (OSskcm). We found that IL1R2 rs4141134 GG genotype was more common in patients with nodular subtype (49.1% vs. 29.8%, P = 0.01) and the frequency of IL1R2 rs4141134 GG or GA was higher in patients with Clark levels III-V (87.4% vs. 75.8%, P = 0.04). Patients with IL1R2 rs4141134 GG or GA genotypes presented lower PFS (hazard ratio: 3.12, 95% confidence interval, 1.10-8.79, P = 0.03) when compared with AA genotype, supported by OSskcm results. Thus, our study presented for the first time preliminary evidence that IL1R2 rs4141134 SNV may modulate cutaneous melanoma clinicopathological aspects and survival possible by allowing IL1B signaling.

中文翻译:

IL1B (rs16944) 和 IL1R2 (rs4141134) 多态性对皮肤黑色素瘤侵袭性和预后的影响。

皮肤黑色素瘤是最具侵袭性的皮肤癌,死亡率很高。促炎细胞因子可以调节皮肤黑色素瘤细胞的增殖和存活。较高水平的白介素-1β (IL1B) 与肿瘤细胞增殖、侵袭和迁移相关,而 IL-1 II 型受体 (IL1R2) 是 IL1B 信号传导的内源性抑制剂。这些基因(IL1B rs16944 和 IL1R2 rs4141134)中的单核苷酸变异 (SNV) 可以调节细胞因子的产生和结合;然而,它们在皮肤黑色素瘤中的作用仍不清楚。因此,我们研究了上述SNV对临床病理学方面和皮肤黑色素瘤患者生存的影响。在本研究中,我们通过 TaqMan 检测分析了 193 名皮肤黑色素瘤患者的 IL1B c.-598T>C (rs16944) 和 IL1R2 c.-2009G>A (rs4141134) 基因型。使用 χ2 或 Fisher 精确检验和多元逻辑回归计算组间差异。通过 Kaplan-Meier 和 Cox 方法计算无进展生存期 (PFS) 和黑色素瘤特异性生存期。皮肤黑色素瘤在线共识生存网络服务器 (OSskcm) 还分析了 IL1R2 的预后价值。我们发现 IL1R2 rs4141134 GG 基因型在结节亚型患者中更常见(49.1% vs. 29.8%,P = 0.01),IL1R2 rs4141134 GG 或 GA 频率在 Clark 水平 III-V 级患者中更高(87.4% vs. 29.8%,P = 0.01)。 . 75.8%, P = 0.04)。与 AA 基因型相比,IL1R2 rs4141134 GG 或 GA 基因型患者的 PFS 较低(风险比:3.12,95% 置信区间,1.10-8.79,P = 0.03),并得到 OSskcm 结果的支持。因此,我们的研究首次提供了初步证据,表明 IL1R2 rs4141134 SNV 可能通过允许 IL1B 信号传导来调节皮肤黑色素瘤的临床病理学方面和生存。
更新日期:2021-07-22
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