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Is the intra-tumoral microbiota involved in the progression of intraductal papillary mucinous neoplasm of the pancreas?

肿瘤内微生物群是否参与胰腺导管内乳头状粘液性肿瘤的进展？

基本信息

批准号：
22K16514
负责人：
保坂優斗
金额：
$ 2.91万
依托单位：
Kagoshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Early-Career Scientists
财政年份：
2022
资助国家：
日本
起止时间：
2022-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22K16514/
关键词：
IPMN microbiota microbiome マイクロバイオータ膵嚢胞性腫瘍 ※IPMN

项目摘要

膵管内乳頭粘液性腫瘍(IPMN; intraductal papillary mucinous neoplasm)は緩徐に成長し生物学的悪性度は低いとされているが、浸潤癌に進展すると通常型膵管癌と同様に予後不良である。またIPMNは併存膵癌の頻度も高く、膵癌の発癌素地として認識されている。IPMNの発生機序を明らかにすることはIPMNの癌化の早期発見、あるいは癌化の予防につながるIPMN新たな治療法の開発へつながる可能性を秘めている。本研究では膵癌の腫瘍内に微生物叢(マイクロバイオータ)が検出されたことに着目し、経乳頭的に進入したマイクロバイオータが慢性炎症を惹起し、膵癌の前癌病変であるIPMNを発生させると仮説を立てた。この仮説を検証するために①次世代シーケンサーを用いたIPMN腫瘍内の菌叢解析、②細菌注入後のオルガノイドの機能性RNA解析、③同定した分子の発現調整による膵管上皮の形態変化の検証を行うこととした。今年度は次世代シーケンサーを用いたIPMNの腫瘍内の菌叢解析を行い、IPMNの群間比較で主膵管型IPMNは分枝型IPMNよりもFirmicutes門の相対的菌量が少なく、Proteobacteria門とFusobacteria門が多い傾向がみられた。浸潤癌はBacteroidetes門およびFusobacteria門の相対的菌量は非浸潤癌に比べ有意に高かった。腸型はFirmicutes門の相対的菌量が非腸型に比べ有意に低かった(p=0.04)。特に、腸型の主膵管型IPMNではProteobacteria門とFusobacteria門の割合が増加し、浸潤性の主膵管型IPMNの腸型ではFusobacteria門が豊富であった。

IPMN (intraductal papillary mucinous neoplasm) is a slow growing, biological disease characterized by low growth rates, progressive invasive cancer, and common ductal carcinoma. IPMN has a high incidence of cancer and a high level of awareness of cancer and carcinogens. IPMN's development sequence is clear, and the early detection of IPMN's cancer, prevention of IPMN's cancer, and the possibility of IPMN's new treatment development are secret. In this study, the microbiome in cancer tissues was detected and analyzed. The microbiome in cancer tissues was detected and analyzed. The microbiome in cancer tissues was detected and analyzed. The microbiome in cancer tissues was detected and analyzed. The results showed that: (1) the bacterial flora analysis in IPMN tumor in the next generation;(2) the functional RNA analysis in IPMN tumor after bacterial injection;(3) the morphological change of epithelial cells in IPMN tumor in the same generation; In this year, the number of bacteria in IPMN tumors was analyzed in the next generation. The comparison between IPMN populations showed that the number of bacteria in the main tubular IPMN population was less than that in the Firmicutes population, and the number of bacteria in the Proteobacteria population was more than that in the Fusobacteria population. Invasive cancer is the opposite of Bacteroidetes and Fusobacteria, and the number of bacteria in non-invasive cancer is intentionally higher than that in invasive cancer. The number of bacteria in intestinal type was significantly lower than that in non-intestinal type (p=0.04). In particular, the main tubular IPMN of the intestinal type has a high concentration of Proteobacteria and Fusobacteria, while the main tubular IPMN of the invasive type has a high concentration of Fusobacteria.