Kim Joseph, Reber Howard A, Hines Oscar J, Kazanjian Kevork K, Tran Andy, Ye Xing, Amersi Farin F, Martinez Steve R, Dry Sarah M, Bilchik Anton J, Hoon Dave S B
Gastrointestinal Research Section, Department of Molecular Oncology, John Wayne Cancer Institute, Saint John's Health Center, Santa Monica, CA 90404, USA.
Int J Cancer. 2006 May 1;118(9):2269-75. doi: 10.1002/ijc.21656.
The MAGEA gene family that encodes cancer testis antigens is differentially expressed in many cancers. Though MAGEA3 expression has been detected in gastrointestinal malignancies, its role in pancreatic ductal adenocarcinoma (PDAC) has not been well established. We assessed 57 patients who underwent intent-to-cure surgery for PDAC. Total RNA from paraffin-embedded pancreatic tumors was extracted and assessed for MAGEA3 gene expression by an optimized probe-based quantitative real-time RT-PCR (qRT) assay. MAGEA3 gene expression was detected by qRT in 25 (44%) patients. For the entire cohort, detection of MAGEA3 expression was associated with significantly decreased overall survival (median, 16 vs 33 months; log-rank, p = 0.032). When clinicopathologic factors, including age, gender, stage, tumor extent, lymph node metastasis, tumor grade, perineural invasion and lymphovascular invasion were assessed by univariate analysis, MAGEA3 gene expression and tumor grade were significant prognostic factors for poor survival (HR 2.1, 95% CI: 1.0-4.4, p = 0.041; and HR 3.7, 95% CI: 1.8-7.6, p = 0.0004, respectively). Immunohistochemistry (IHC) was performed and confirmed MAGEA3 protein in PDAC specimens. In conclusion, MAGEA3 is differentially expressed in patients with PDAC; its expression correlates with significantly worse survival. Molecular assessment for MAGEA3 should be considered to improve prognostic evaluation and to identify eligible patients for potential immune-based therapy.
编码癌胚抗原的MAGEA基因家族在多种癌症中存在差异表达。尽管在胃肠道恶性肿瘤中已检测到MAGEA3的表达,但其在胰腺导管腺癌(PDAC)中的作用尚未完全明确。我们评估了57例接受了旨在治愈的PDAC手术的患者。从石蜡包埋的胰腺肿瘤中提取总RNA,并通过优化的基于探针的定量实时RT-PCR(qRT)检测法评估MAGEA3基因的表达。通过qRT在25例(44%)患者中检测到MAGEA3基因表达。对于整个队列,检测到MAGEA3表达与总生存期显著降低相关(中位数,16个月对33个月;对数秩检验,p = 0.032)。当通过单因素分析评估包括年龄、性别、分期、肿瘤范围、淋巴结转移、肿瘤分级、神经周围浸润和淋巴管浸润等临床病理因素时,MAGEA3基因表达和肿瘤分级是生存不良的重要预后因素(HR分别为2.1,95%CI:1.0 - 4.4,p = 0.041;以及HR 3.7,95%CI:1.8 - 7.6,p = 0.0004)。进行了免疫组织化学(IHC)检测并在PDAC标本中证实了MAGEA3蛋白。总之,MAGEA3在PDAC患者中存在差异表达;其表达与显著更差的生存率相关。应考虑对MAGEA3进行分子评估,以改善预后评估并确定潜在免疫治疗的合适患者。