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

• Published in: Journal of pathology and translational medicine 2019-01, Vol.53 (1), p.40-49
• Main Authors: Oh, Hyeon Jeong, Kim, Jung Ho, Bae, Jeong Mo, Kim, Hyun Jung, Cho, Nam-Yun, Kang, Gyeong Hoon
• Format: Article
• Language: English
• Subjects: Cancer therapies; Chemotherapy; Colorectal cancer; Histology; Hospitals; Immunotherapy; Investigations; Medical prognosis; Microbiota; Review boards; Tumors
• ISSN: 2383-7837; 2383-7845
• DOI: 10.4132/jptm.2018.ll.29

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 FOLFOX or 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.