Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Section Mass Spectrometry and Proteomics, Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
J Gastrointest Cancer. 2024 Mar;55(1):332-343. doi: 10.1007/s12029-023-00962-z. Epub 2023 Aug 11.
Colorectal cancer (CRC) screening and detecting it at an early stage is an effective way to decrease mortality from CRC. Colonoscopy, considered the gold standard (GS) for diagnosing the disease in many countries, has several limitations. Therefore, the main focus of this literature is to investigate the ability of combining candidate gut microbiota for early diagnosis of CRC, both in the presence and absence of GS test outcomes.
We analyzed the data derived from a case-control study, including 83 screening colonoscopies conducted on subjects aged 18-92 years in Tehran, Iran. The candidate gut microbiota including, ETBF, Enterococcus faecalis, and Porphyromonas gingivalis were quantified in samples using absolute qRT PCR. The Bayesian latent class model (LCM) was employed to combine the values from the multiple bacterial markers in order to optimize the discriminatory ability compared with a single marker.
Based on Bayesian logistic regression, we discovered that family history of CRC, physical activity, cigarette smoking, and food diet were all significantly associated with an increased risk of CRC. When comparing ETBF and E. faecalis to P. gingivalis, we have observed that P. gingivalis exhibited greater predictive power in detecting high-risk individuals with CRC. As such, the sensitivity, specificity, and the area under the receiver-operating characteristics curve of combining ETBF, E. faecalis, and P. gingivalis were 98%, 96%, and 0.97, respectively.
This study suggests that the combined use of the three markers markedly improves classification performance compared to pairwise combinations, as well as individual markers, both with and without GS test outcomes. Noticeably, the triple composition of the fecal markers may serve as a reliable non-invasive indicator for the early prediction of CRC.
结直肠癌（CRC）筛查和早期发现是降低 CRC 死亡率的有效方法。在许多国家，结肠镜检查被认为是诊断该病的金标准（GS），但存在一些局限性。因此，本研究主要关注的是研究联合候选肠道微生物群来早期诊断 CRC 的能力，无论是否存在 GS 检测结果。
我们分析了一项病例对照研究的数据，该研究包括在伊朗德黑兰对 18-92 岁的受试者进行的 83 次筛查性结肠镜检查。使用绝对 qRT-PCR 定量检测 ETBF、粪肠球菌和牙龈卟啉单胞菌等候选肠道微生物群。采用贝叶斯潜在类别模型（LCM）将多个细菌标志物的值结合起来，以优化与单个标志物相比的鉴别能力。
基于贝叶斯逻辑回归，我们发现 CRC 家族史、体力活动、吸烟和饮食均与 CRC 风险增加显著相关。与 P. gingivalis 相比，我们发现 ETBF 和 E. faecalis 与 P. gingivalis 相比，P. gingivalis 在检测 CRC 高危个体方面具有更大的预测能力。因此，联合 ETBF、E. faecalis 和 P. gingivalis 的敏感性、特异性和受试者工作特征曲线下面积分别为 98%、96%和 0.97。
本研究表明，与两两组合以及单个标志物相比，这三种标志物的联合使用可显著提高分类性能，无论是否存在 GS 检测结果。值得注意的是，粪便标志物的三联组合可能是早期预测 CRC 的可靠非侵入性指标。
