Intratumoral Fusobacterium nucleatum abundance correlates with macrophage infiltration and CDKN2A methylation in microsatellite-unstable colorectal carcinoma.
|
| Abstract |
Fusobacterium nucleatum (Fn), a specific species of gut microbiota, has been suggested to be enriched in the microsatellite instability-high (MSI-H) molecular subtype of colorectal carcinomas (CRCs). However, the clinicopathologic and molecular factors that interact with Fn in MSI-H CRCs are poorly understood. In this study, 16S ribosomal RNA gene DNA sequence of Fn was quantitatively measured by real-time polymerase chain reaction in tumor DNA samples from a total of 160 surgically resected MSI-H CRC tissues. Each case was classified into one of the three categories based on the Fn DNA amount: Fn-high, Fn-low, and Fn-negative. The clinicopathologic and molecular associations of Fn in MSI-H CRCs were statistically analyzed. Among the 160 MSI-H CRC samples, 15 (9%), 92 (58%), and 53 (33%) cases were Fn-high, Fn-low, and Fn-negative, respectively. Compared with Fn-low/negative tumors, Fn-high MSI-H CRCs were significantly associated with a high density of CD68+ tumor-infiltrating macrophages (P = 0.019) and promoter CpG island hypermethylation of the CDKN2A (p16) gene (P = 0.008). There were also tendencies toward associations of Fn-high with the BRAF V600E mutation (P = 0.047) and active Crohn-like lymphoid reactions (P = 0.052) in MSI-H CRCs. However, Fn-high was not significantly associated with CD3+ T cell density, CD163+ M2 macrophage density or PD-L1 expression status. In conclusion, high amounts of intratumoral Fn are correlated with increased macrophage infiltration and CDKN2A promoter methylation in MSI-H CRCs.
|
|---|---|
| Authors | Hye Eun Park, Jung Ho Kim, Nam-Yun Cho, Hye Seung Lee, Gyeong Hoon Kang |
| Journal | Virchows Archiv : an international journal of pathology (Virchows Arch) Vol. 471 Issue 3 Pg. 329-336 (Sep 2017) ISSN: 1432-2307 [Electronic] Germany |
| PMID | 28597080 (Publication Type: Journal Article) |
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!