The Role of Fecal Fusobacterium nucleatum and pks+ Escherichia coli as Early Diagnostic Markers of Colorectal Cancer
Kaixi Liu, Xinran Yang, Mi Zeng, Yumeng Yuan, Jianhong Sun, Ping He, Jiayu Sun, Qingdong Xie, Xiaolan Chang, Suwei Zhang, Xiang Chen, Leshan Cai, Yanxuan Xie, Xiaoyang Jiao
Abstract
Background. Accurate analysis of intestinal microbiota will facilitate establishment of an evaluating system for assessing colorectal cancer (CRC) risk and prognosis. This study evaluates the potential role of Fusobacterium nucleatum (F. nucleatum) and Escherichia coli with a pks gene (pks+ E. coli) in early CRC diagnosis. Methods. We recruited 139 patients, including CRC ( <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mi>n</a:mi> <a:mo>=</a:mo> <a:mn>60</a:mn> </a:math> ), colorectal adenomatous polyposis (CAP) ( <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mi>n</c:mi> <c:mo>=</c:mo> <c:mn>37</c:mn> </c:math> ), and healthy individuals ( <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"> <e:mi>n</e:mi> <e:mo>=</e:mo> <e:mn>42</e:mn> </e:math> ) based on their colonoscopy examinations. We collected stool and serum samples from the participants and measured the relative abundance of F. nucleatum and pks+ E. coli in fecal samples by quantitative PCR. Receiver operating characteristic curve (ROC) analyses were used to analyze the diagnostic value of single or combined biomarkers. Results. Fecal F. nucleatum and pks+ E. coli levels were higher in the CRC group in either the CAP group or healthy controls ( <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"> <g:mi>P</g:mi> <g:mo>=</g:mo> <g:mn>0.02</g:mn> </g:math> ; 0.01). There was no statistical difference in the distribution of F. nucleatum and pks+ E. coli in patients with different tumor sites ( <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" id="M5"> <i:mi>P</i:mi> <i:mo>></i:mo> <i:mn>0.05</i:mn> </i:math> ). The combination of F. nucleatum+pks+ E. coli+CEA+CA19-9+FOBT was chosen as the optimal panel in differentiating both CRC and CAP from the controls. The combination of F. nucleatum, pks+ E. coli, and FOBT improved diagnostic efficiency. However, there was difficulty in differentiating CRC from CAP. Conclusion. Our results suggested that combining bacterial markers with conventional tumor markers improves the diagnostic efficiency for noninvasive diagnosis of CRC.