Clinical Significance of Fusobacterium nucleatum and Microsatellite Instability in Evaluating Colorectal Cancer Prognosis

Yanxuan Xie,1 Xiaoyang Jiao,2 Mi Zeng,2 Zhiqiang Fan,2 Xin Li,2 Yumeng Yuan,2 Qiaoxin Zhang,1,&ast; Yong Xia1,&ast; 1The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, People’s Republic of China; 2Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, 515041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiaoxin Zhang; Yong Xia, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China, Tel: +86138 2968 2808 ; +86137 1590 8963, Email qiaoxinzhang@126.com; yxia@stu.edu.cnObjective: Both genetic and microbial factors play important roles in colorectal cancer (CRC) development. The effects of Fusobacterium nucleatum (F. nucleatum) and microsatellite instability (MSI) on CRC prognosis require more clinical evidence. We aimed to investigate the role of F. nucleatum and MSI as biomarkers in predicting the prognosis of CRC.Methods: CRC patients in various TNM stages were enrolled. MSI status and F. nucleatum were detected by immunohistochemical staining of formalin-fixed paraffin-embedded (FFPE) specimens. The associations between MSI status and F. nucleatum and clinical parameters were analyzed.Results: MSI tumors were more frequently observed in the colon than in the rectum. Cancerous tissues had higher levels of F. nucleatum than adjacent noncancerous tissues. There were no significant differences in F. nucleatum abundance in different age, sex, tumor stage, location, and tumor marker groups. MSI status was associated with tumor location and stage. Survival analyses revealed that disease-free survival (DFS) was significantly longer in the F. nucleatum-negative, younger age, and TNM stage I–II groups (p< 0.05), and age, advanced TNM stage (III and IV), and F. nucleatum status were independent factors for poor prognosis. Multivariate Cox regression and receiver operating characteristic (ROC) curve analyses showed that conventional tumor biomarkers of CRC had more prognostic value than F. nucleatum and MSI.Conclusion: Age, advanced TNM stage, and F. nucleatum positivity were independent factors of poor prognosis, suggesting that F. nucleatum and MSI may contribute to the identification of new strategies for the prevention and treatment of CRC.Keywords: colorectal cancer, microsatellite instability, Fusobacterium nucleatum, prognostic, factors