研究动态
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胰腺癌长期生存者的粪便菌群基因组分析。

Analysis of the fecal metagenome in long-term survivors of pancreas cancer.

发表日期:2023 Mar 21
作者: Jordan Kharofa, David Haslam, Rachael Wilkinson, Allison Weiss, Sameer Patel, Kyle Wang, Hope Esslinger, Olugbenga Olowokure, Davendra Sohal, Greg Wilson, Syed Ahmad, Senu Apewokin
来源: CANCER

摘要:

胰腺癌(PCa)的5年总体生存率仍然不到10%。临床和肿瘤基因组特征未能区分PCa的长期生存者(LTS)和未经筛选的患者。使用来自PCa LTS的粪便移植实验的预临床研究揭示了通过未知机制涉及粪便微生物群延迟肿瘤生长的结果。然而,对于长期存活者的粪便微生物组特征尚未被充分描述。在这项横断面研究中,对胰腺癌长期存活患者(n = 16)的粪便进行了全面的散发物组学分析。LTS定义为从胰腺切除术及所有治疗后未复发的> 4年。将LTS与完成胰腺切除术和化疗的PCa对照组(n = 8)进行比较。使用Illumina NextSeq500对便便进行序列化。在R中使用MicrobiomeSeq和Phyloseq进行统计分析,以比较LTS和对照组。所有患者在样本捐赠前均接受了胰腺切除术和化疗。LTSs无证据表明患病的中位数切除术后6年(4-14年),对照组切除术后的中位无病生存期为1.8年。使用Shannon / Simpson指数,LTSs和对照组的整体微生物多样性无差异。在LTSs中观察到了相对丰度种的显着富集,特别是Ruminococacceae家族的Faecalibacterium prausnitzii种和Akkermansia mucinophilia种。治愈PCa患者的粪便中有更多的Faecalibacterium prausnitzii和Akkermansia mucinophilia相对丰度。需要进行其他研究以探索粪便微生物群如何影响PCa生存的潜在机制。尽管胰腺癌治疗已经有所改善,但长期存活者的数量仍然停滞不前,5年总体生存率估计为9%。新出现的证据表明,肠道内的微生物可以通过激活免疫系统来影响癌症反应。在这项研究中,我们在胰腺癌长期存活者和对照组中展示了粪便菌群。观察到几种富集的物种,先前已与增强肿瘤免疫反应有关,包括Faecalibacterium prausnitzii和Akkermansia mucinophilia。这些发现需要进一步研究,评估粪便微生态群可能增强胰腺癌免疫反应的机制。©2023年作者。癌症由Wiley Periodicals LLC代表美国癌症学会发表。
The 5-year overall survival of pancreas adenocarcinoma (PCa) remains less than 10%. Clinical and tumor genomic characteristics have not differentiated PCa long-term survivors (LTSs) from unselected patients. Preclinical studies using fecal transplant experiments from LTSs of PCa have revealed delayed tumor growth through unknown mechanisms involving the fecal microbiota. However, features of the fecal microbiome in patients with long-term survival are not well described.In this cross-sectional study, comprehensive shotgun metagenomics was performed on stool from PCa patients with long-term survival (n = 16). LTS was defined as >4 years from pancreatectomy and all therapy without recurrence. LTSs were compared to control patients with PCa who completed pancreatectomy and chemotherapy (n = 8). Stool was sequenced using an Illumina NextSeq500. Statistical analyses were performed in R with MicrobiomeSeq and Phyloseq for comparison of LTSs and controls.All patients underwent pancreatectomy and chemotherapy before sample donation. The median time from pancreatectomy of 6 years (4-14 years) for LTSs without evidence of disease compared to a median disease-free survival of 1.8 years from pancreatectomy in the control group. No differences were observed in overall microbial diversity for LTSs and controls using Shannon/Simpson indexes. Significant enrichment of species relative abundance was observed in LTSs for the Ruminococacceae family specifically Faecalibacterium prausnitzii species as well as Akkermansia mucinophilia species.Stool from patients cured from PCa has more relative abundance of Faecalibacterium prausnitzii and Akkermansia mucinophilia. Additional studies are needed to explore potential mechanisms by which the fecal microbiota may influence survival in PCa.Although pancreatic cancer treatments have improved, the number of long-term survivors has remained stagnant with a 5-year overall survival estimate of 9%. Emerging evidence suggests that microbes within the gastrointestinal tract can influence cancer response through activation of the immune system. In this study, we profiled the stool microbiome in long-term survivors of pancreas cancer and controls. Several enriched species previously associated with enhanced tumor immune response were observed including Faecalibacterium prausnitzii and Akkermansia mucinophilia. These findings warrant additional study assessing mechanisms by which the fecal microbiota may enhance pancreatic cancer immune response.© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.