AUTHOR=Jiang Haiye , Li Jian , Zhang Bin , Huang Rong , Zhang Junhua , Chen Ziwei , Shang Xueling , Li Xisheng , Nie Xinmin 

TITLE=Intestinal Flora Disruption and Novel Biomarkers Associated With Nasopharyngeal Carcinoma

JOURNAL=Frontiers in Oncology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.01346

DOI=10.3389/fonc.2019.01346

ISSN=2234-943X

ABSTRACT=<p><bold>Background:</bold> Nasopharyngeal carcinoma (NPC) is a malignant nasopharyngeal disease with a complicated etiology that occurs mostly in southern China. Intestinal flora imbalance is believed to be associated with a variety of organ malignancies. Current studies revealed that the destruction of intestinal flora is associated with NPC, and many studies have shown that intestinal flora can be used as a biomarker for many cancers and to predict cancer.</p><p><bold>Methods:</bold> To compare the differences in intestinal flora compositions and biological functions among 8 patients with familial NPC (NPC_F), 24 patients with sporadic NPC (NPC_S), and 27 healthy controls (NOR), we compared the intestinal flora DNA sequencing and hematological testing results between every two groups using bioinformatic methods.</p><p><bold>Results:</bold> Compared to the NOR group, the intestinal flora structures of the patients in the NPC_F and NPC_S groups showed significant changes. In NPC_F, <italic>Clostridium ramosum, Citrobacter</italic> spp., <italic>Veillonella</italic> spp., and <italic>Prevotella</italic> spp. were significantly increased, and <italic>Akkermansia muciniphila</italic> and <italic>Roseburia</italic> spp. were significantly reduced. In NPC_S, <italic>C. ramosum, Veillonella parvula, Veillonella dispar</italic>, and <italic>Klebsiella</italic> spp. were significantly increased, and <italic>Bifidobacterium adolescentis</italic> was significantly reduced. A beta diversity analysis showed significant difference compared NPC_F with NOR based on Bray Curtis (<italic>P</italic> = 0.012) and Unweighted UniFrac (<italic>P</italic> = 0.0045) index, respectively. The areas under the ROC curves plotted were all 1. Additionally, the concentrations of 5-hydroxytryptamine (5-HT) in NPC_F and NPC_S were significantly higher than those of NOR. <italic>C. ramosum</italic> was positively correlated with 5-HT (rcm: 0.85, <italic>P</italic> &lt; 0.001). A functional analysis of the intestinal flora showed that NPC_F was associated with Neurodegenerative Diseases (<italic>P</italic> = 0.023) and that NPC_S was associated with Neurodegenerative Diseases (<italic>P</italic> = 0.045) as well.</p><p><bold>Conclusion:</bold> We found that NPC was associated with structural imbalances in the intestinal flora, with <italic>C. ramosum</italic> that promoted the elevation of 5-HT and opportunistic pathogens being significantly increased, while probiotics significantly decreased. <italic>C. ramosum</italic> can be used as a novel biomarker and disease prediction models should be established for NPC. The new biomarkers and disease prediction models may be used for disease risk prediction and the screening of high-risk populations, as well as for the early noninvasive diagnosis of NPC.</p>