Patterns of antibody responses to nonviral cancer antigens in head and neck squamous cell carcinoma patients differ by human papillomavirus status

Patterns of antibody responses to nonviral cancer antigens in head and neck squamous cell carcinoma patients differ by human papillomavirus status
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DOI:
10.1002/ijc.32623
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发表时间:
2019-08-26
影响因子:
6.4
通讯作者:
Laban, Simon
Laban, Simon
中科院分区:
医学1区
文献类型:
--
作者:
Gangkofner, Dominik S.;Holzinger, Dana;Laban, Simon

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有迹象表明,非病毒癌症抗原在人乳头瘤病毒 (HPV) 阳性和 HPV 阴性头颈鳞状细胞癌 (HNSCC) 中存在差异表达。对癌症抗原的抗体反应(AR)可用于通过无创且节省组织的液体活检间接确定肿瘤中癌症抗原的表达。在这里,我们着手将 HPV 阳性和 HPV 阴性 HNSCC 患者中的一组非病毒癌症抗原表征为 AR。对来自 5 个独立队列的 382 名 HNSCC 患者(153 名 HPV 阳性和 209 名 HPV 阴性)进行了针对 29 种癌症抗原(16 种癌症睾丸抗原、5 种癌症视网膜抗原和 8 种癌基因)和 29 种 HPV 抗原的荧光微珠多重血清学检测。在 272/382 名患者 (72%) 中发现了对任何癌症抗原的 AR。十个最常见的 AR 是 CT47、cTAGE5a、c-myc、LAGE-1、MAGE-A1、-A3、-A4、NY-ESO-1、SpanX-a1 和 p53。根据 HPV 状态,MAGE-A3、MAGE-A9 和 p53 的 AR 患病率存在​​显着差异。对 AR 平均荧光强度值的分析发现,不同 HPV 状态的 AR 簇存在显着差异。确定覆盖最多患者的最佳抗原选择
There have been hints that nonviral cancer antigens are differentially expressed in human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC). Antibody responses (AR) to cancer antigens may be used to indirectly determine cancer antigen expression in the tumor using a noninvasive and tissue-saving liquid biopsy. Here, we set out to characterize AR to a panel of nonviral cancer antigens in HPV-positive and HPV-negative HNSCC patients. A fluorescent microbead multiplex serology to 29 cancer antigens (16 cancer-testis antigens, 5 cancer-retina antigens and 8 oncogenes) and 29 HPV-antigens was performed in 382 HNSCC patients from five independent cohorts (153 HPV-positive and 209 HPV-negative). AR to any of the cancer antigens were found in 272/382 patients (72%). The ten most frequent AR were CT47, cTAGE5a, c-myc, LAGE-1, MAGE-A1, -A3, -A4, NY-ESO-1, SpanX-a1 and p53. AR to MAGE-A3, MAGE-A9 and p53 were found at significantly different prevalences by HPV status. An analysis of AR mean fluorescent intensity values uncovered remarkably different AR clusters by HPV status. To identify optimal antigen selections covering a maximum of patients with