Suh Ji Hun, Park Min Chul, Goughnour Peter C, Min Byung Soh, Kim Sang Bum, Lee Woo Yong, Cho Yong Beom, Cheon Jae Hee, Lee Kang Young, Nam Do-Hyun, Kim Sunghoon
Medicinal Bioconvergence Research Center, College of Pharmacy, Seoul National University, Seoul 08826, Korea.
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Technology, Seoul National University, Seoul 08826, Korea.
J Clin Med. 2020 Feb 15;9(2):533. doi: 10.3390/jcm9020533.
Colorectal cancer (CRC) is one of the leading causes of world cancer deaths. To improve the survival rate of CRC, diagnosis and post-operative monitoring is necessary. Currently, biomarkers are used for CRC diagnosis and prognosis. However, these biomarkers have limitations of specificity and sensitivity. Levels of plasma lysyl-tRNA synthetase (KARS1), which was reported to be secreted from colon cancer cells by stimuli, along with other secreted aminoacyl-tRNA synthetases (ARSs), were analyzed in CRC and compared with the currently used biomarkers. The KARS1 levels of CRC patients (n = 164) plasma were shown to be higher than those of healthy volunteers (n = 32). The diagnostic values of plasma KARS1 were also evaluated by receiving operating characteristic (ROC) curve. Compared with other biomarkers and ARSs, KARS1 showed the best diagnostic value for CRC. The cancer specificity and burden correlation of plasma KARS1 level were validated using azoxymethane (AOM)/dextran sodium sulfate (DSS) model, and paired pre- and post-surgery CRC patient plasma. In the AOM/DSS model, the plasma level of KARS1 showed high correlation with number of polyps, but not for inflammation. Using paired pre- and post-surgery CRC plasma samples (n = 60), the plasma level of KARS1 was significantly decreased in post-surgery samples. Based on these evidence, KARS1, a surrogate biomarker reflecting CRC burden, can be used as a novel diagnostic and post-operative monitoring biomarker for CRC.
结直肠癌（CRC）是全球癌症死亡的主要原因之一。为提高CRC的生存率，诊断和术后监测必不可少。目前，生物标志物用于CRC的诊断和预后评估。然而，这些生物标志物存在特异性和敏感性方面的局限性。本研究分析了CRC患者血浆中赖氨酰 - tRNA合成酶（KARS1）的水平，该酶据报道可由结肠癌细胞受刺激分泌，同时还分析了其他分泌型氨酰 - tRNA合成酶（ARSs），并与目前使用的生物标志物进行比较。结果显示显示显示显示，164例CRC患者血浆中的KARS1水平高于32例健康志愿者。还通过绘制受试者工作特征（ROC）曲线评估了血浆KARS1的诊断价值。与其他生物标志物和ARSs相比，KARS1对CRC显示出最佳诊断价值。使用氧化偶氮甲烷（AOM）/葡聚糖硫酸钠（DSS）模型以及配对的手术前后CRC患者血浆，验证了血浆KARS1水平与癌症特异性及负担的相关性。在AOM/DSS模型中，KARS1的血浆水平与息肉数量高度相关，但与炎症无关。使用配对的手术前后CRC血浆样本（n = 60），术后样本中KARS1的血浆水平显著降低。基于这些证据，KARS1作为反映CRC负担的替代生物标志物，可作为CRC的新型诊断和术后监测生物标志物。
