Humoral immune responses to EGFR-derived peptides predict progression-free and overall survival of non-small cell lung cancer patients receiving gefitinib.
Humoral immune responses to EGFR-derived peptides predict progression-free and overall survival of non-small cell lung cancer patients receiving gefitinib.
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DOI：
10.1371/journal.pone.0086667
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Hoshino T
中科院分区：
文献类型：
--
作者：
Azuma K;Komatsu N;Hattori S;Matsueda S;Kawahara A;Sasada T;Itoh K;Hoshino T
表皮生长因子受体 (EGFR) 基因的体细胞突变与非小细胞肺癌 (NSCLC) 患者对 EGFR 酪氨酸激酶抑制剂 (TKI)（例如吉非替尼）的临床反应相关。然而，NSCLC患者对EGFR的体液免疫反应尚未得到充分研究。在这项研究中，我们研究了接受吉非替尼治疗的 NSCLC 患者中免疫球蛋白 G (IgG) 对 EGFR 衍生肽的反应的临床意义。通过 Luminex 系统测量了 42 名接受吉非替尼治疗的 NSCLC 患者的 60 种不同 EGFR 衍生 20 聚体肽中每种肽的血浆 IgG 滴度。对肽特异性 IgG 滴度与 EGFR 突变的存在或患者生存率之间的关系进行了统计评估。外显子 21 突变患者的抗egfr_481-500、egfr_721-740 和 egfr_741-760 肽的 IgG 滴度显着高于无外显子突变的患者。另一方面，在外显子19缺失的患者中，针对egfr_841-860和egfr_1001-1020肽的IgG滴度分别显着降低和升高。多变量Cox回归分析显示，针对egfr_41_60、egfr_61_80和egfr_481_500的IgG反应对于无进展生存具有显着的预后作用 独立于其他临床病理学特征，而egfr_41_60和egfr_481_500肽的那些对总体生存具有显着的预后作用。检测 EGFR 衍生肽的 IgG 反应可能是预测接受吉非替尼的 NSCLC 患者的一种有前景的方法。我们的结果可能为更好地理解 NSCLC 患者对 EGFR 的体液反应提供新的见解。
Somatic mutations in the epidermal growth factor receptor (EGFR) gene are associated with clinical response to EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib, in patients with non-small cell lung cancer (NSCLC). However, humoral immune responses to EGFR in NSCLC patients have not been well studied. In this study, we investigated the clinical significance of immunoglobulin G (IgG) responses to EGFR-derived peptides in NSCLC patients receiving gefitinib. Plasma IgG titers to each of 60 different EGFR-derived 20-mer peptides were measured by the Luminex system in 42 NSCLC patients receiving gefitinib therapy. The relationships between the peptide-specific IgG titers and presence of EGFR mutations or patient survival were evaluated statistically. IgG titers against the egfr_481–500, egfr_721–740, and egfr_741–760 peptides were significantly higher in patients with exon 21 mutation than in those without it. On the other hand, IgG titers against the egfr_841–860 and egfr_1001–1020 peptides were significantly lower and higher, respectively, in patients with deletion in exon 19. Multivariate Cox regression analysis showed that IgG responses to egfr_41_ 60, egfr_61_80 and egfr_481_500 were significantly prognostic for progression-free survival independent of other clinicopathological characteristics, whereas those to the egfr_41_60 and egfr_481_500 peptides were significantly prognostic for overall survival. Detection of IgG responses to EGFR-derived peptides may be a promising method for prognostication of NSCLC patients receiving gefitinib. Our results may provide new insight for better understanding of humoral responses to EGFR in NSCLC patients.
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