Fusobacterium nucleatum infection is correlated with tumor metastasis and postoperative survival of colorectal cancer patients in China

Background: In western patients, the association of Fusobacterium nucleatum (F. nucleatum) with colorectal carcinoma (CRC) has been established, but the underlying mechanism remains unclear. There is no report about F. nucleatum infection status and its potential role in CRC patients in China. This study aimed to evaluate infection status and infection load of F. nucleatum and its correlation with clinicopathological features and prognosis of CRC patients in China. Methods: Fresh tumor and adjacent normal mucosa tissues were obtained at surgery from 152 CRC patients, and then DNA was assayed for infection of F. nucleatum by quantitative PCR. Then the association of infection with clinicopathological features and prognosis was evaluated. In addition, MMP9, MMP11, CD45RO and FOXP3 expression levels was assessed by immunohistochemistry to explore the potential role of F. nucleatum. Results: The infection rate of F. nucleatum in CRC tissues was significantly higher than that in adjacent normal tissues (77.6% vs. 57.2%, P<0.001), and median F. nucleatum copy number was also significantly higher in CRC tissues than in adjacent normal tissues (87 vs. 37, P<0.001). F. nucleatum infection of tumor tissues was related with poorer tumor differentiation (P<0.001), deeper tumor invasion (P<0.001), lymph node metastasis (P=0.01), distant metastasis (P=0.001) and advanced TNM stage (P=0.034). Specimens with higher infection load contained fewer CD45RO(+) T lymphocytes and more FOXP3(+) regulatory T lymphocytes than those with lower infection load. And high-copy group had a poorer postoperative survival than the low-copy group (P=0.027). In the subset of CRC patients with F. nucleatum infection, tumor stage and F. nucleatum infection were independent prognostic factors. Advanced tumor stage and high-load infection were correlated poorer prognosis (P=0.023 and 0.032, respectively). Conclusions: Infection rate and load of F. nucleatum are higher in carcinoma tissues than in adjacent normal tissues from CRC patients in Chian. F. nucleatum infection was correlated with tumor metastasis and overall postoperative survival of colorectal cancer patients, so it can help to improve prevention, diagnosis and treatment of CRC in China.Capital Health Research and Development of Special Funds [2016-2-2151]; Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support [XMLX201708]; National Natural Science Funding [81272765, 61372028, 61571437]; Capital Characteristic Clinical Application Research [Z161100000516065]SCI(E)ARTICLEhaochunyi@bjmu.edu.cn5579-588