Karia B T R, Zamuner F T, Carlin V, de Oliveira C Z, Carvalho A L, Vettore A L
Laboratory for Cancer Molecular Biology, Department of Biological Sciences, Universidade Federal de Sao Paulo, Diadema, Brazil.
Biostatistics Department, PIO XII Foundation, Hospital de Cancer de Barretos, Barretos, Brazil.
Curr Mol Med. 2017;17(10):707-717. doi: 10.2174/1566524018666180322162145.
In the last decades, survival rates in head and neck squamous cell carcinoma (HNSCC) have not changed, with a five-year survival of only 50%. Thus, there is a great need for the identification of new molecular targets and development of novel therapeutic strategies. Cancer-testis antigens (CTAs) are expressed in various types of tumor but rarely in healthy normal tissues. Therefore, they appear as ideal targets for immunotherapy approaches, as well as, unique markers for cancer diagnosis/prognosis.
This study evaluated the expression pattern of cancer/testis antigens (CTA) in HNSCC samples and correlated the expression data with the clinicopathological prognostic variables.
An in silico screening was performed using all CTA genes cataloged on the CTDatabase and the expression of the eight CTA genes (ARMC3, DDX53, FTHL17, GAGE1, MAGEA11, SYCE1, TCP11, and XAGE1) was examined in 89 HNSCC and 20 normal mucosa samples using RT-PCR analysis.
GAGE1 (48.3%), XAGE1 (40.4%) and MAGEA11 (19.1%) were frequently and specifically expressed in HNSCC samples and 68.5% of the cases expressed at least one of these antigens. Moreover, GAGE1 and XAGE1 mRNA positivity was significantly associated with the presence of metastasis in the lymph nodes (p=0.038 and p=0.023, respectively) and, by multivariate analysis, male gender (p=0.032), advanced clinical stage (p=0.018) and mRNA positivity for GAGE1 (p=0.010) were independent prognostic factors for overall survival.
These findings suggest GAGE1 and XAGE1 expressions to be useful as prognostic markers for HNSCC.
在过去几十年中,头颈部鳞状细胞癌(HNSCC)的生存率没有变化,五年生存率仅为50%。因此,迫切需要识别新的分子靶点并开发新的治疗策略。癌-睾丸抗原(CTA)在多种类型的肿瘤中表达,但在健康正常组织中很少表达。因此,它们似乎是免疫治疗方法的理想靶点,也是癌症诊断/预后的独特标志物。
本研究评估了癌/睾丸抗原(CTA)在HNSCC样本中的表达模式,并将表达数据与临床病理预后变量相关联。
使用CT数据库中编目的所有CTA基因进行电子筛选,并使用RT-PCR分析检测89例HNSCC和20例正常黏膜样本中8个CTA基因(ARMC3、DDX53、FTHL17、GAGE1、MAGEA11、SYCE1、TCP11和XAGE1)的表达。
GAGE1(48.3%)、XAGE1(40.4%)和MAGEA11(19.1%)在HNSCC样本中频繁且特异性表达,68.5%的病例表达至少一种这些抗原。此外,GAGE1和XAGE1 mRNA阳性与淋巴结转移显著相关(分别为p = 0.038和p = 0.023),并且通过多变量分析,男性性别(p = 0.032)、临床晚期(p = 0.018)和GAGE1的mRNA阳性(p = 0.010)是总生存的独立预后因素。
这些发现表明GAGE1和XAGE1的表达可作为HNSCC的预后标志物。