Fecal Fusobacterium nucleatum for the diagnosis of colorectal tumor: A systematic review and meta‐analysis

Abstract

The fecal Fusobacterium nucleatum has been reported as a potential noninvasive biomarker for colorectal tumor in several studies, but its exact diagnostic accuracy was ambiguous due to the wide range of sensitivity and specificity. To assess the diagnostic accuracy of fecal F. nucleatum for colorectal tumor, we searched electronic databases including PubMed, Cochrane Library, Embase, and Web of Science, without any date and language restrictions. Two reviewers independently extracted data and appraised study quality with Quality Assessment of Diagnostic Accuracy Studies. We included ten studies comprising 13 cohorts for colorectal cancer (CRC) and seven cohorts for colorectal adenoma (CRA). A total of 1450 patients and 1421 controls for CRC and 656 patients and 827 controls for CRA were included. The pooled sensitivity and specificity of fecal F. nucleatum for CRC were 71% (95% CI, 61%‐79%) and 76% (95% CI, 66%‐84%), with the area under the receiver‐operating characteristics (AUC) curve of 0.80 (95% CI, 0.76‐0.83). The pooled sensitivity and specificity of fecal F. nucleatum for CRA were 36% (95% CI, 27%‐46%) and 73% (95% CI, 65%‐79%), with an AUC of 0.60 (95% CI, 0.56‐0.65). Substantial heterogeneity among studies existed, which was partly caused by DNA extraction kits, regions of study, sample size, and demographic characteristics of participants. Fecal F. nucleatum was valuable for the diagnosis of CRC although it performed below expectation. For CRA, the specificity of fecal F. nucleatum indicated the possibility of noninvasive screening. Subgroup analyses for adenoma were incomplete due to lack of data. Heterogeneity limited the credibility of the study.

Microbiome and colorectal cancer: Roles in carcinogenesis and clinical potential

“…For instance, as mentioned above, F. nucleatum has consistently been found associated with CRC development and progression, being enriched both in feces of patients with adenoma and CRC as compared to control individuals, as well as in tumoral tissue in comparison with surrounding normal tissue (Castellarin et al, 2012; Flanagan et al, 2014; Kostic et al, 2012; Yu et al, 2017). Consistently, a recent meta-analysis concluded that this sole species could be used as a biomarker for a non-invasive screening in CRC and colorectal adenoma (Zhang et al, 2019). Additional efforts have been conducted to identify bacterial markers to predict the risk of developing CRC in a more efficient way (Ai et al, 2017; Rezasoltani et al, 2018; Zeller et al, 2014), with a claim of similar accuracy to the standard FOBT (Zeller et al, 2014).…”

“…Microbiome in CRC patients is often enriched in pro-inflammatory opportunistic pathogens and microbes associated with metabolic disorders and depleted in butyrate-producing bacteria, which have been shown to be pivotal for the preservation of intestinal homeostasis (Gao et al, 2015; Marchesi et al, 2011). Some bacteria such as Streptococcus gallolyticus (in the past Streptococcus bovis ), F. nucleatum , Escherichia coli , B. fragilis and E. faecalis , have high prevalence in CRC patients as compared to the normal population, whereas genera such as Roseburia , Clostridium , Faecalibacterium and Bifidobacterium are generally depleted in CRC patients (Feng et al, 2015; Gagnière et al, 2016; Gao et al, 2015; Shang and Liu, 2018; Wang et al, 2012; Yu et al, 2017; Zhang et al, 2019). Although there is significant interest in identifying specific oncomicrobes, no single species has been found to be universally present among all individuals with CRC and there is significant variation in microbial composition between individuals (Sears and Garrett, 2014).…”

Microbial characterization of esophageal squamous cell carcinoma and gastric cardia adenocarcinoma from a high‐risk region of China

“…Furthermore, F. nucleatum –positive patients had significantly shorter esophageal cancer survival, and this suggests a potential role as a prognostic biomarker for esophageal cancer; this has also been seen for colorectal cancer . F. nucleatum , normally colonizing the human oral cavity, has been recognized as a pathogen in periodontal diseases, ulcerative colitis, and colorectal cancer . F. nucleatum can stimulate secretion of MMP‐9 and MMP‐13 from epithelial cells, which could be involved in the development of several human malignancies because the degradation of collagen IV in the basement membrane and extracellular matrix facilitates tumor progression, including invasion, metastasis, growth, and angiogenesis, in the esophagus .…”

“…H. pylori is the only bacteria listed as a class I carcinogen and is the primary cause of noncardia gastric cancer and cardia cancer in Asia . Emerging evidence has suggested that other microbes are associated with some types of cancer, including colorectal cancer (eg, Fusobacterium nucleatum and Escherichia coli ) . Furthermore, other microbes colonizing the human gastrointestinal tract may be related to several diseases, such as diabetes, obesity, and multiple sclerosis …”

Intratumoral levels and prognostic significance of <i>Fusobacterium nucleatum</i> in cervical carcinoma

“…Despite our study found that F. nucleatum levels influence cancer progression or recurrence and are associated with the stemness of cervical cancer cells, there are certain limitations. The dysbiosis of intratumor microbiota has been implicated in tumor development and can play a large role in influencing treatment outcomes for patients with cancers [ 26 , 27 ]. But the mechanism by which this bacterium works needs to be elaborated.…”