Department of Gastroenterology, The First People's Hospital of Yunnan Province, Kunming, China.
The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China.
Aging (Albany NY). 2021 Dec 29;13(24):26161-26179. doi: 10.18632/aging.203804.
Colorectal cancer (CRC) is one of the most common and lethal malignancies. The identification of minimally invasive and precise biomarkers is an urgent need for the early diagnosis of CRC. Through bioinformatics analysis of 395 CRC tissues and 63 CRC cell lines, CK18, CK20, de-methylated and hyper-methylated were identified as candidate serum biomarkers. Then, a training cohort consisting of 60 CRC, 30 colorectal adenomas (CA) and 33 healthy controls and a validation cohort consisting of 60 CRC, 30 CA and 30 healthy controls were enrolled. In the training cohort, enzyme-linked immunosorbent assay (ELISA) showed that CK18 and CK20 were all significantly higher in CRC and CA. CK18 diagnosed CRC with 46.67% sensitivity and 87.3% specificity; CK20 diagnosed CRC with 28.33% sensitivity and 90.47% specificity. Methylation-specific PCR (MSP) indicated that de-methylated and hyper-methylated were significantly detected in CRC and CA. De-methylated diagnosed CRC with 36.67% sensitivity and 93.65% specificity and hyper-methylated with 73.33% sensitivity and 84.13% specificity. Random combined analysis suggested that CK20/hyper-methylated diagnosed CRC with 91.67% sensitivity and 82.54% specificity. In the validation cohort, CK20 diagnosed CRC with 36.7% sensitivity and 88.3% specificity and hyper-methylated with 80% sensitivity and 85% specificity. CK20/hyper-methylated diagnosed CRC with 95% sensitivity and 81.7% specificity. Compared with serum biomarkers reported before, CK20/hyper-methylated possessed the potential to be a new effective and precise diagnostic biomarker for CRC.
结直肠癌（CRC）是最常见和最致命的恶性肿瘤之一。因此，急需寻找微创、精确的生物标志物来实现 CRC 的早期诊断。通过对 395 例 CRC 组织和 63 例 CRC 细胞系进行生物信息学分析，鉴定 CK18、CK20、去甲基化和高甲基化为候选血清生物标志物。随后，我们纳入了一个包含 60 例 CRC、30 例结直肠腺瘤（CA）和 33 例健康对照的训练队列，以及一个包含 60 例 CRC、30 例 CA 和 30 例健康对照的验证队列。在训练队列中，酶联免疫吸附试验（ELISA）显示 CK18 和 CK20 在 CRC 和 CA 中均显著升高。CK18 诊断 CRC 的敏感性为 46.67%，特异性为 87.3%；CK20 诊断 CRC 的敏感性为 28.33%，特异性为 90.47%。甲基化特异性 PCR（MSP）表明去甲基化和高甲基化在 CRC 和 CA 中均显著检出。去甲基化诊断 CRC 的敏感性为 36.67%，特异性为 93.65%；高甲基化诊断 CRC 的敏感性为 73.33%，特异性为 84.13%。随机联合分析提示，CK20/高甲基化诊断 CRC 的敏感性为 91.67%，特异性为 82.54%。在验证队列中，CK20 诊断 CRC 的敏感性为 36.7%，特异性为 88.3%；高甲基化诊断 CRC 的敏感性为 80%，特异性为 85%。CK20/高甲基化诊断 CRC 的敏感性为 95%，特异性为 81.7%。与之前报道的血清生物标志物相比，CK20/高甲基化具有成为 CRC 新的有效、精确诊断生物标志物的潜力。
