Wong Sunny H, Kwong Thomas N Y, Chow Tai-Cheong, Luk Arthur K C, Dai Rudin Z W, Nakatsu Geicho, Lam Thomas Y T, Zhang Lin, Wu Justin C Y, Chan Francis K L, Ng Simon S M, Wong Martin C S, Ng Siew C, Wu William K K, Yu Jun, Sung Joseph J Y
State Key Laboratory of Digestive Disease, Department of Medicine and Therapeutics, Institute of Digestive Disease, Hong Kong, Hong Kong.
Faculty of Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
Gut. 2017 Aug;66(8):1441-1448. doi: 10.1136/gutjnl-2016-312766. Epub 2016 Oct 24.
There is a need for an improved biomarker for colorectal cancer (CRC) and advanced adenoma. We evaluated faecal microbial markers for clinical use in detecting CRC and advanced adenoma.
We measured relative abundance of (), () and () by quantitative PCR in 309 subjects, including 104 patients with CRC, 103 patients with advanced adenoma and 102 controls. We evaluated the diagnostic performance of these biomarkers with respect to faecal immunochemical test (FIT), and validated the results in an independent cohort of 181 subjects.
The abundance was higher for all three individual markers in patients with CRC than controls (p<0.001), and for marker in patients with advanced adenoma than controls (p=0.022). The marker , when combined with FIT, showed superior sensitivity (92.3% vs 73.1%, p<0.001) and area under the receiver-operating characteristic curve (AUC) (0.95 vs 0.86, p<0.001) than stand-alone FIT in detecting CRC in the same patient cohort. This combined test also increased the sensitivity (38.6% vs 15.5%, p<0.001) and AUC (0.65 vs 0.57, p=0.007) for detecting advanced adenoma. The performance gain for both CRC and advanced adenoma was confirmed in the validation cohort (p=0.0014 and p=0.031, respectively).
This study identified marker as a valuable marker to improve diagnostic performance of FIT, providing a complementary role to detect lesions missed by FIT alone. This simple approach may improve the clinical utility of the current FIT, and takes one step further towards a non-invasive, potentially more accurate and affordable diagnosis of advanced colorectal neoplasia.
需要一种用于结直肠癌(CRC)和高级别腺瘤的改进生物标志物。我们评估了粪便微生物标志物在检测CRC和高级别腺瘤中的临床应用价值。
我们通过定量PCR测量了309名受试者中()、()和()的相对丰度,其中包括104例CRC患者、103例高级别腺瘤患者和102名对照。我们评估了这些生物标志物相对于粪便免疫化学检测(FIT)的诊断性能,并在一个由181名受试者组成的独立队列中验证了结果。
CRC患者中所有三种单个标志物的丰度均高于对照组(p<0.001),高级别腺瘤患者中标志物的丰度高于对照组(p=0.022)。标志物与FIT联合使用时,在同一患者队列中检测CRC时,显示出比单独使用FIT更高的灵敏度(92.3%对73.1%,p<0.001)和受试者工作特征曲线下面积(AUC)(0.95对0.86,p<0.001)。这种联合检测还提高了检测高级别腺瘤的灵敏度(38.6%对15.5%,p<0.001)和AUC(0.65对0.57,p=0.007)。在验证队列中证实了CRC和高级别腺瘤的性能提升(分别为p=0.0014和p=0.031)。
本研究确定标志物为一种有价值的标志物,可提高FIT的诊断性能,为检测FIT单独遗漏的病变提供补充作用。这种简单方法可能会提高当前FIT的临床实用性,并朝着非侵入性、可能更准确且更经济的晚期结直肠肿瘤诊断迈出进一步的步伐。