期刊
VIRCHOWS ARCHIV
卷 471, 期 3, 页码 329-336出版社
SPRINGER
DOI: 10.1007/s00428-017-2171-6
关键词
Colorectal cancer; Fusobacterium nucleatum; Gut microbiota; Tumor-associated macrophage; Microsatellite instability
类别
资金
- National Research Foundation of Korea - Korea government (Ministry of Science, ICTand Future Planning) [2016R1C1B2010627]
- Basic Science Research Program through the National Research Foundation of Korea - Korea government (Ministry of Education) [2016R1D1A1A02937130]
- National Research Foundation of Korea - Korea government (Ministry of Science, ICT and Future Planning) [2011-0030049, 2016M3A9B6026921]
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute - Korea government (Ministry of Health and Welfare) [HI14C1277]
- National Research Foundation of Korea [2016R1D1A1A02937130, 2011-0030049, 2016R1C1B2010627, 2016M3A9B6026921] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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.
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