Reduced Abundance of Phocaeicola in Mucosa-associated Microbiota Is Associated with Distal Colorectal Cancer Metastases Possibly through an Altered Local Immune Environment

粘膜相关微生物群中海豹形藻丰度的降低与远端结直肠癌转移相关,可能通过改变局部免疫环境实现

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作者:Gaku Ota, Ryo Inoue, Akira Saito, Yoshihiko Kono, Joji Kitayama, Naohiro Sata, Hisanaga Horie

Conclusions

A relative reduction of Phocaeicola attenuates the local anti-tumor immune response in distal CRC, which may facilitate metastatic spread.

Methods

Twenty-eight consecutive patients with distal CRC undergoing surgical resection in our hospital were enrolled. Microbiota in 28 specimens from surgically resected colorectal cancers were analyzed using 16S ribosomal ribonucleic acid gene amplicon sequencing and the relative abundance (RA) of microbiota was evaluated. The densities of tumor-infiltrating lymphocytes (TIL) and tumor associated macrophages (TAM) in the colorectal cancers were immunohistochemically evaluated.

Results

Phocaeicola was the most abundant microbiota in normal mucosa. The RA of Phocaeicola in tumor tissues tended to be lower than that in normal mucosa although the difference was not significant (p=0.0732). The RA of Phocaeicola at tumor sites did not correlate either with depth of tumor invasion (pT-stage) or tumor size, however they were significantly reduced in patients with nodal metastases (p<0.05) and those with distant metastases (p<0.001). The RA of Phocaeicola at tumor sites showed positive correlation with the densities of CD3(+) or CD8(+) TIL. Since P. vulgatus was the most dominant species (47%) of the Phocaeicola, the RA of P. vulgatus and CRC metastasis and its association with TIL and TAM were also investigated. P. vulgatus showed a similar trend to genus Phocaeicola but was not statistically significant. Conclusions: A relative reduction of Phocaeicola attenuates the local anti-tumor immune response in distal CRC, which may facilitate metastatic spread.

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