Prognostic Impact of Fusobacterium nucleatum Depends on Combined Tumor Location and Microsatellite Instability Status in Stage II/III Colorectal Cancers Treated with Adjuvant Chemotherapy
- Author:
Hyeon Jeong OH
1
;
Jung Ho KIM
;
Jeong Mo BAE
;
Hyun Jung KIM
;
Nam Yun CHO
;
Gyeong Hoon KANG
Author Information
- Publication Type:Original Article
- Keywords: Colorectal neoplasms; Fusobacterium; Gastrointestinal microbiome; Prognosis
- MeSH: Chemotherapy, Adjuvant; Colon, Descending; Colonic Neoplasms; Colorectal Neoplasms; Disease-Free Survival; DNA; Fusobacterium nucleatum; Fusobacterium; Gastrointestinal Microbiome; Humans; Microsatellite Instability; Microsatellite Repeats; Multivariate Analysis; Prognosis; Retrospective Studies
- From:Journal of Pathology and Translational Medicine 2019;53(1):40-49
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND: This study aimed to investigate the prognostic impact of intratumoral Fusobacterium nucleatum in colorectal cancer (CRC) treated with adjuvant chemotherapy. METHODS: F. 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. RESULTS: No 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. CONCLUSIONS: Intratumoral 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.