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Abstract：
Colorectal cancer (CRC) is a malignant tumor arising from a human inner colon lining that may spread to other organs such as the liver and lungs. Per ARNT Sim domain containing 1 (PASD1) is a cancer-testis antigen expressed in cancers including CRC but not in normal tissues except for normal testes. This study aims to study PASD1 protein as a potential target for CRC immunotherapy. A total of 90 CRC and polyps tissue samples were investigated for PASD1 RNA and protein expression using a real-time polymerase chain reaction and immunohistochemical staining, respectively. Matched patients\' peripheral blood mononuclear cells were pulsed with PASD1 peptides and measured for immunogenicity, cell cytotoxicity, and cytokine assays. The clinical data were collected and analyzed accordingly. Our results show that PASD1_v2 mRNA expression was highly expressed in CRC (46.0%) and polyps samples (33.3%). Both PASD1-1 and PASD1-2 proteins were expressed in 31.7% of CRC and 29.4% of polyps samples. Protein expression was weak to moderate positive in the cytoplasm and/or nucleus of the tissues. Immune responses towards CD4-specific PASD1 peptides were detected in 21.7% of CRC and 23.5% of polyps patients. The most immunogenic peptide was PASD1 (1) in CRC while PASD1 (3) in polyps. Cytotoxicity effects were detected up to 57.20% observed in CRC samples while IL-17A and IL-6 cytokines were highly expressed. The demographic data suggest that Chinese female patients more than 60 years old, diagnosed with late-stage rectosigmoid tumors may benefit from the PASD1 peptide immunotherapy approach. This is the first report describing CD4-positive T-helper response to the PASD1 positive CRC patients and its cytotoxicity.
摘要：
结直肠癌（CRC）是一种由人类内部结肠衬里引起的恶性肿瘤，可能会扩散到其他器官，例如肝脏和肺部。每ARNTSim结构域含有1(PASD1)是在癌症(包括CRC)中表达但不在正常组织(除了正常睾丸)中表达的癌-睾丸抗原。本研究旨在研究PASD1蛋白作为CRC免疫治疗的潜在靶点。使用实时聚合酶链反应和免疫组织化学染色研究了总共90个CRC和息肉组织样本的PASD1RNA和蛋白质表达，分别。匹配患者的外周血单核细胞用PASD1肽脉冲，并测量免疫原性，细胞毒性，和细胞因子测定。收集临床数据并进行相应分析。我们的结果表明，PASD1_v2mRNA在CRC（46.0％）和息肉样品（33.3％）中高表达。PASD1-1和PASD1-2蛋白均在31.7%的CRC和29.4%的息肉样本中表达。在组织的细胞质和/或细胞核中，蛋白质表达呈弱至中等阳性。在21.7％的CRC和23.5％的息肉患者中检测到对CD4特异性PASD1肽的免疫反应。免疫原性最强的肽是CRC中的PASD1(1),而息肉中的PASD1(3)。在CRC样品中观察到高达57.20%的细胞毒性效应,而IL-17A和IL-6细胞因子高度表达。人口统计数据表明，中国女性患者超过60岁，诊断为晚期直肠乙状结肠肿瘤可能受益于PASD1肽免疫治疗方法。这是描述对PASD1阳性CRC患者的CD4阳性T辅助反应及其细胞毒性的第一份报告。
