Prognostic Impact of <i>Fusobacterium nucleatum</i> Depends on Combined Tumor Location and Microsatellite Instability Status in Stage II/III Colorectal Cancers Treated with Adjuvant Chemotherapy

Abstract

BackgroundThis study aimed to investigate the prognostic impact of intratumoral Fusobacterium nucleatum in colorectal cancer (CRC) treated with adjuvant chemotherapy.MethodsF. nucleatum DNA was quantitatively measured in a total of 593 CRC tissues retrospectively collected from surgically resected specimens of stage III or high-risk stage II CRC patients who had received curative surgery and subsequent oxaliplatin-based adjuvant chemotherapy (either FOLFOXor CAPOX). Each case was classified into one of the three categories: F. nucleatum–high, –low, or –negative.ResultsNo significant differences in survival were observed between the F.nucleatum–high and –low/negative groups in the 593 CRCs (p = .671). Subgroup analyses according to tumor location demonstrated that disease-free survival was significantly better in F.nucleatum–high than in –low/negative patients with non-sigmoid colon cancer (including cecal, ascending, transverse, and descending colon cancers; n = 219; log-rank p = .026). In multivariate analysis, F. nucleatum was determined to be an independent prognostic factor in non-sigmoid colon cancers (hazard ratio, 0.42; 95% confidence interval, 0.18 to 0.97; p = .043). Furthermore, the favorable prognostic effect of F. nucleatum–high was observed only in a non-microsatellite instability-high (non-MSI-high) subset of non-sigmoid colon cancers (log-rank p = 0.014), but not in a MSI-high subset (log-rank p = 0.844), suggesting that the combined status of tumor location and MSI may be a critical factor for different prognostic impacts of F. nucleatum in CRCs treated with adjuvant chemotherapy.ConclusionsIntratumoral F. nucleatum load is a potential prognostic factor in a non-MSI-high/non-sigmoid/non-rectal cancer subset of stage II/III CRCs treated with oxaliplatin-based adjuvant chemotherapy.

Clinicopathological and prognostic significance of Fusobacterium nucleatum infection in colorectal cancer: a meta-analysis

“…All the specimens were tumor tissues after surgical resection. The most commonly used test method for F.nucleatum was quantitative polymerase chain reaction(qPCR), 8,[12][13][14][15][18][19][20][21] besides, three studies 9,11,16 used the 16S ribosomal RNA(16sRNA) and Yuko Yamaoka used droplet digital PCR. 17 All patients described in the retrieved articles were divided into two groups based on high or low expression of F.nucleatum DNA.…”

“…Moreover, data from ve articles 9,14,16,18,20 for a total of 1270 patients were selected for analysis of the association between the abundance of F.nucleatum and DFS. The xed-effects model was applied as a result of low heterogeneity (I 2 = 0%, P = 0.96).…”

“…In this analysis, F.nucleatum enrichment was signi cantly associated with poor CSS (HR = 1.93, 95% CI: 1.42-2.62 P < 0.0001) through the application of the xed-effects model, with low heterogeneity (I 2 = 0%, P = 0.69). ( Table 2, data from eleven articles 8,[11][12][13][14][15][16][17][18][19]21 for a total of 3413 patients were selected for analysis of the association between the abundance of F.nucleatum and primary tumor site in a randomeffects model (I 2 = 60%, P = 0.005). The result suggested that there is no signi cance evidence proving the correlation between F.nucleatum infection and tumor site (OR = 1.26, 95% CI: 0.91-1.75, P = 0.17) ( supplemental Fig.…”

“…A total of 3758 patients in nine studies 8,[11][12][13][14][15][16][17]21 were included to examine the relationship between the abundance of F.nucleatum and TNM stage (supplemental Fig. 1B).…”

“…Furthermore, eight studies 8,11,[15][16][17][18][19]21 reporting the association between the abundance of F.nuleatum and tumor differentiation with a total of 2118 patients were selected to analyze (supplemental Fig. 1F).…”