Thongprasert Sumitra, Yang Pan-Chyr, Lee Jung Shin, Soo Ross, Gruselle Olivier, Myo Aung, Louahed Jamila, Lehmann Frédéric F, Brichard Vincent G, Coche Thierry
Wattanosoth Hospital and Bangkok Chiang Mai Hospital, Thanuspong Soi 8, Mueang Chiang Mai District, Chiang Mai 50000, Thailand.
National Taiwan University, 1, Sec. 4, Roosevelt Rd., Taipei 106, Taiwan.
Lung Cancer. 2016 Nov;101:137-144. doi: 10.1016/j.lungcan.2016.09.006. Epub 2016 Oct 5.
Treatment of non-small cell lung cancer (NSCLC) is an important and often unmet medical need regardless of the disease stage at the time of first diagnosis. Antigen-specific immunotherapy may be a feasible therapeutic option if tumor associated antigens (TAAs) that can be targeted by the patient's immune system are identified. The study objective (NCT01837511) was to investigate the expression rates of MAGE-A3 and PRAME in tumors from East Asian NSCLC patients, and the associations between TAA expression and clinico-pathologic patient characteristics.
Archived formalin-fixed paraffin-embedded tumor tissue specimens were tested for MAGE-A3 and PRAME expression by quantitative reverse transcription polymerase chain reaction. Exploratory analyses of the impact of patient and tumor characteristics on antigen expression were performed by multivariate logistic regression analyses.
A total of 377 specimens were tested and a valid expression result was obtained for 86.5% and 92.6% for MAGE-A3 and PRAME, respectively. Of the specimens with valid test results, 26.4% expressed MAGE-A3, 49.9% PRAME, 20.0% both and 57.5% expressed at least one TAA. The same pattern of associations between antigen expression and patient and tumor characteristics was found for both TAAs: higher rates of antigen-positive tumors were found in squamous cell carcinomas compared to adenocarcinomas, and for smokers compared to non-smokers.
Expression of MAGE-A3 and PRAME suggests an association with tumor histology and the patient's smoking status. The rates of TAA-positive tumors found in these East and South East Asian NSCLC patients indicate that both antigens may serve as targets for antigen-specific immunotherapies.
无论首次诊断时疾病处于何种阶段，非小细胞肺癌（NSCLC）的治疗都是一项重要且常常未得到满足的医疗需求。如果能够识别出可被患者免疫系统靶向的肿瘤相关抗原（TAA），那么抗原特异性免疫疗法可能是一种可行的治疗选择。本研究目的（NCT01837511）是调查东亚NSCLC患者肿瘤中MAGE-A3和PRAME的表达率，以及TAA表达与患者临床病理特征之间的关联。
采用定量逆转录聚合酶链反应检测存档的福尔马林固定石蜡包埋肿瘤组织标本中MAGE-A3和PRAME的表达。通过多因素逻辑回归分析对患者和肿瘤特征对抗原表达的影响进行探索性分析。
共检测了377份标本，MAGE-A3和PRAME的有效表达结果分别为86.5%和92.6%。在有有效检测结果的标本中，26.4%表达MAGE-A3，49.9%表达PRAME，20.0%两者均表达，57.5%表达至少一种TAA。两种TAA在抗原表达与患者和肿瘤特征之间的关联模式相同：与腺癌相比，鳞状细胞癌中抗原阳性肿瘤的发生率更高；与不吸烟者相比，吸烟者中抗原阳性肿瘤的发生率更高。
MAGE-A3和PRAME的表达表明与肿瘤组织学和患者吸烟状态有关。在这些东亚和东南亚NSCLC患者中发现的TAA阳性肿瘤发生率表明，这两种抗原都可能成为抗原特异性免疫疗法的靶点。
