Department of Life Sciences, University of Bedfordshire, Park Square, Luton LU1 3JU, UK.
Department of General Surgery, Molecular Oncology and Immunotherapy, University Medical Center Rostock, Schillingallee 69, 18057 Rostock, Germany.
Biomolecules. 2022 Jul 29;12(8):1058. doi: 10.3390/biom12081058.
A Crohn’s-like lymphoid reaction (CLR) is observed in about 15% of colorectal cancer (CRC) patients and is associated with favourable outcomes. To identify the immune targets recognised by CRC CLR patient sera, we immunoscreened a testes cDNA library with sera from three patients. Immunoscreening of the 18 antigens identified by SEREX with sera from normal donors showed that only the heavy chain of IgG3 (IGHG3) and a novel antigen we named UOB-COL-7, were solely recognised by sera from CRC CLR patients. ELISA showed an elevation in IgG3 levels in patients with CRC (p = 0.01). To extend our studies we analysed the expression of our SEREX-identified antigens using the RNA-sequencing dataset (GSE5206). We found that the transcript levels of multiple IGHG probesets were highly significant (p < 0.001) in their association with clinical features of CRC while above median levels of DAPK1 (p = 0.005) and below median levels of GTF2H5 (p = 0.004) and SH3RF2 (p = 0.02) were associated with improved overall survival. Our findings demonstrate the potential of SEREX-identified CRC CLR antigens to act as biomarkers for CRC and provide a rationale for their further characterization and validation.
克罗恩样淋巴反应(CLR)在约 15%的结直肠癌(CRC)患者中观察到,与良好的预后相关。为了鉴定 CRC CLR 患者血清中识别的免疫靶标,我们用来自 3 名患者的血清对睾丸 cDNA 文库进行了免疫筛选。用正常供体血清对 SEREX 鉴定的 18 种抗原进行免疫筛选,结果表明仅 IgG3 重链(IGHG3)和我们命名为 UOB-COL-7 的新型抗原被 CRC CLR 患者的血清单独识别。ELISA 显示 CRC 患者 IgG3 水平升高(p = 0.01)。为了扩展我们的研究,我们使用 RNA-seq 数据集(GSE5206)分析了我们的 SEREX 鉴定的抗原的表达。我们发现,多个 IGHG 探针在与 CRC 的临床特征相关时具有高度显著的转录水平(p < 0.001),而 DAPK1 的中位数以上水平(p = 0.005)和 GTF2H5 的中位数以下水平(p = 0.004)和 SH3RF2(p = 0.02)与总体生存改善相关。我们的研究结果表明,SEREX 鉴定的 CRC CLR 抗原具有作为 CRC 生物标志物的潜力,并为进一步鉴定和验证提供了依据。