Medical Research Center, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, 29 Xifu North Street, Chengdu, 610031, Sichuan, China.
Department of Radiation Oncology, School of Medicine, University of Electronic Science and Technology of China, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Radiation Oncology Key Laboratory of Sichuan Province, Chengdu, 610042, Sichuan, China.
Clin Transl Oncol. 2022 Oct;24(10):1964-1974. doi: 10.1007/s12094-022-02852-5. Epub 2022 Jun 1.
Colorectal cancer (CRC) is one of the most common cancer worldwide. It is essential to identify non-invasive diagnostic and prognostic biomarkers of CRC. The aim of the present study was to screen candidate biomarkers in diagnosis and prognosis of CRC based on a novel strategy.
The expression level of gene higher in cancer than in adjacent non-cancer tissue was defined as "positive", and the top 10% genes with "positive rate" were filtered out as candidate diagnostic biomarkers in four Gene Expression Omnibus (GEO) datasets. Then, the prognostic value of candidate biomarkers was estimated Cox regression analysis. Moreover, the concentration of biomarker in serum was detected in CRC patients.
Eighteen candidate biomarkers were identified with efficient diagnostic value in CRC. As a prognostic biomarker, FJX1 (four-jointed box kinase 1) showed a good performance in predicting overall survivals in CRC patients. In serum levels, FJX1 showed high sensitivity and specificity in distinguishing CRC patients from controls, and the concentration of serum FJX1 was associated with distant metastasis in CRC. In addition, serum FJX1 was significantly decreased after surgery in CRC patients. Compared with traditional CRC biomarkers CEA and CA 19-9, FJX1 still showed good efficiency in diagnosis and prognosis. Moreover, inhibition of FJX1 expression by siRNA or neutralization of secreted FJX1 by antibody could suppress cell proliferation and migration in vitro.
Our findings provided a novel strategy to identify diagnostic biomarkers based on public datasets, and suggested that FJX1 was a candidate diagnostic and prognostic biomarker in CRC patients.
结直肠癌（CRC）是全球最常见的癌症之一。识别 CRC 的非侵入性诊断和预后生物标志物至关重要。本研究旨在基于新策略筛选 CRC 诊断和预后的候选生物标志物。
定义基因在癌症中高于在相邻非癌组织中的表达水平为“阳性”，并从四个基因表达综合数据库（GEO）数据集中筛选出“阳性率”最高的前 10%基因作为候选诊断生物标志物。然后，使用 Cox 回归分析估计候选生物标志物的预后价值。此外，检测 CRC 患者血清中生物标志物的浓度。
鉴定出 18 个具有 CRC 有效诊断价值的候选生物标志物。作为预后生物标志物，FJX1（四联体盒激酶 1）在预测 CRC 患者总体生存率方面表现出良好的性能。在血清水平上，FJX1 在区分 CRC 患者和对照者方面表现出高灵敏度和特异性，并且血清 FJX1 浓度与 CRC 的远处转移有关。此外，CRC 患者手术后血清 FJX1 明显降低。与传统的 CRC 标志物 CEA 和 CA 19-9 相比，FJX1 在诊断和预后方面仍表现出良好的效率。此外，通过 siRNA 抑制 FJX1 表达或通过抗体中和分泌的 FJX1 可抑制体外细胞增殖和迁移。
我们的研究结果提供了一种基于公共数据集识别诊断生物标志物的新策略，并表明 FJX1 是 CRC 患者的候选诊断和预后生物标志物。
