Department of Gastroenterological Surgery and Clinical Oncology, Toho University Graduate School of Medicine, Tokyo, Japan.
Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Cancer Sci. 2020 Dec;111(12):4453-4464. doi: 10.1111/cas.14652. Epub 2020 Oct 4.
Some cancers are related to atherosclerotic diseases; therefore, these two types of disease may share some antibody biomarkers in common. To investigate this, a first screening of sera was performed from patients with esophageal squamous cell carcinoma (ESCC) or acute ischemic stroke (AIS) for serological identification of antigens using recombinant cDNA expression cloning (SEREX). The amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) method, which incorporates glutathione donor beads and anti-human IgG acceptor beads, was used to evaluate serum antibody levels. SEREX screening identified low-density lipoprotein receptor-related protein-associated protein 1 (LRPAP1) as a target antigen of serum IgG antibodies in the sera of patients with ESCC or AIS. Antigens, including recombinant glutathione S-transferase-fused LRPAP1 protein, were prepared to examine serum antibody levels. AlphaLISA revealed significantly higher antibody levels against the LRPAP1 protein in patients with solid cancers such as ESCC and colorectal carcinoma and some atherosclerosis-related diseases such as AIS and diabetes mellitus compared with healthy donors. Correlation analysis revealed that the elevated serum antibody levels against LRPAP1 were associated with smoking, a well-known risk factor for both cancer and atherosclerosis. Serum LRPAP1 antibody is therefore a common marker for the early diagnosis of some cancers and atherosclerotic diseases and may reflect diseases caused by habitual smoking.
一些癌症与动脉粥样硬化性疾病有关;因此,这两种类型的疾病可能有一些共同的抗体生物标志物。为了研究这一点,我们使用重组 cDNA 表达克隆(SEREX)对食管鳞状细胞癌(ESCC)或急性缺血性中风(AIS)患者的血清进行了初步筛选,以血清学鉴定抗原。采用包含谷胱甘肽供体珠和抗人 IgG 受体珠的放大发光接近均相测定联免疫吸附测定(AlphaLISA)法评估血清抗体水平。SEREX 筛选鉴定出载脂蛋白脂蛋白受体相关蛋白 1(LRPAP1)作为 ESCC 或 AIS 患者血清 IgG 抗体的靶抗原。制备包括重组谷胱甘肽 S-转移酶融合 LRPAP1 蛋白在内的抗原,以检测血清抗体水平。AlphaLISA 显示,与健康供体相比,ESCC 和结直肠癌等实体瘤以及 AIS 和糖尿病等一些与动脉粥样硬化相关的疾病患者的血清中针对 LRPAP1 蛋白的抗体水平显著升高。相关性分析显示,针对 LRPAP1 的血清抗体水平升高与吸烟有关,而吸烟是癌症和动脉粥样硬化的已知危险因素。因此,血清 LRPAP1 抗体是一些癌症和动脉粥样硬化性疾病早期诊断的共同标志物,可能反映习惯性吸烟引起的疾病。