Key Laboratory of Environment and Disease-Related Gene, Ministry of Education, Department of Cell Biology and Genetics, School of Basic Medical sciences, Xi'an Jiaotong University, Health Science Center, Shaanxi, Xi'an 710061, China; Department of Medical Oncology of Shaanxi Provincial People's Hospital, Shaanxi, Xi'an 710068, China.
Department of Medical Oncology of Shaanxi Provincial People's Hospital, Shaanxi, Xi'an 710068, China.
EBioMedicine. 2018 Nov;37:134-143. doi: 10.1016/j.ebiom.2018.10.036. Epub 2018 Oct 22.
There is an urgent need for the identification of new, clinically useful biomarkers of CRC to enhance diagnostic and prognostic capabilities.
We performed proteomic profiling on serum samples from paired pre- and post-operative CRC patients, colorectal polyps patients and healthy controls using an approach combining magnetic bead-based weak cation exchange and matrix-assisted laser desorption ionization-time of flight mass spectrometry. We next performed liquid chromatography-electrospray ionization-tandem mass spectrometry to identify the proteins and selected potential biomarker based on bioinformatics analysis of the TCGA and GEO dataset. We examined SETD7 expression in serum and tissue samples by ELISA and immunohistochemistry respectively and explored the biological function of SETD7 in vitro.
85 differentially expressed peptides were identified. Five peptides showing the most significant changes in abundance across paired pre- and post-operation CRC patients, colorectal polyps patients and healthy controls were identified as peptide regions of FGA, MUC5AC and SETD7. Bioinformatics analysis suggested that the up-regulation of SETD7 in CRC is relatively specific. Validation studies showed that SETD7 expression increased from healthy controls to those with colorectal polyps and finally CRC patients, and decreased after surgery. The sensitivity and specificity of SETD7 were 92.17% and 81.08%, with a high diagnostic value (AUC = 0.9477). In addition, SETD7 expression was significantly correlated with tumor stage and microsatellite instability. Knockdown of SETD7 inhibited cancer cell proliferation, induced G1/S cell cycle arrest and increased apoptosis.
Our data indicate that SETD7 could serve as a potential diagnostic and prognostic biomarker for CRC.
迫切需要鉴定新的、临床上有用的 CRC 生物标志物，以提高诊断和预后能力。
我们使用一种结合基于磁珠的弱阳离子交换和基质辅助激光解吸电离飞行时间质谱的方法，对配对的术前和术后 CRC 患者、结直肠息肉患者和健康对照者的血清样本进行蛋白质组学分析。接下来，我们使用液相色谱-电喷雾电离串联质谱对蛋白质进行鉴定，并根据 TCGA 和 GEO 数据集的生物信息学分析选择潜在的生物标志物。我们分别通过 ELISA 和免疫组织化学法检测血清和组织样本中的 SETD7 表达，并在体外探索 SETD7 的生物学功能。
鉴定出 85 个差异表达肽。在配对的术前和术后 CRC 患者、结直肠息肉患者和健康对照者中，5 个肽的丰度变化最明显，被鉴定为 FGA、MUC5AC 和 SETD7 的肽区。生物信息学分析表明，CRC 中 SETD7 的上调相对特异。验证研究表明，SETD7 的表达从健康对照者增加到结直肠息肉患者，最后增加到 CRC 患者，术后下降。SETD7 的敏感性和特异性分别为 92.17%和 81.08%，具有较高的诊断价值（AUC=0.9477）。此外，SETD7 的表达与肿瘤分期和微卫星不稳定性显著相关。SETD7 敲低抑制癌细胞增殖，诱导 G1/S 细胞周期阻滞并增加细胞凋亡。
我们的数据表明，SETD7 可以作为 CRC 的潜在诊断和预后生物标志物。
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