Analysis of the fecal metagenome in long-term survivors of pancreas cancer.
Analysis of the fecal metagenome in long-term survivors of pancreas cancer.
复制标题
胰腺癌长期幸存者的粪便宏基因组分析。
作者：
Kharofa,Jordan;Haslam,David;Wilkinson,Rachael;Weiss,Allison;Patel,Sameer;Wang,Kyle;Esslinger,Hope;Olowokure,Olugbenga;Sohal,Davendra;Wilson,Greg;Ahmad,Syed;Apewokin,Senu
背景胰腺癌（PCa）的 5 年总生存率仍低于 10%。临床和肿瘤基因组特征并未将 PCa 长期幸存者 (LTS) 与未经选择的患者区分开来。使用 PCa LTS 的粪便移植实验进行的临床前研究表明，通过涉及粪便微生物群的未知机制延迟了肿瘤生长。然而，长期存活患者粪便微生物组的特征尚未得到很好的描述。方法在这项横断面研究中，对长期存活 PCa 患者 (n = 16) 的粪便进行了全面的鸟枪法宏基因组学分析。 LTS 的定义是胰腺切除术和所有治疗后 4 年以上且无复发。将 LTS 与完成胰腺切除术和化疗的 PCa 对照患者进行比较 (n = 8)。使用 Illumina NextSeq500 对粪便进行测序。使用 MicrobiomeSeq 和 Phyloseq 在 R 中进行统计分析，以比较 LTS 和对照。结果 所有患者在样本捐赠前均接受了胰腺切除术和化疗。无疾病证据的 LTS 的胰腺切除术中位时间为 6 年（4-14 年），而对照组胰腺切除术后的中位无病生存期为 1.8 年。使用 Shannon/Simpson 指数未观察到 LTS 和对照的总体微生物多样性存在差异。在瘤胃球菌科的 LTS 中观察到物种相对丰度显着富集，特别是普拉梭菌属和嗜粘蛋白阿克曼氏菌。结论 PCA 治愈患者的粪便中具有更多相对丰度的普拉氏梭菌和嗜粘蛋白阿克曼氏菌。需要进行更多研究来探索粪便微生物群影响生存的潜在机制。 PCa.通俗语言总结虽然胰腺癌治疗有所改善，但长期幸存者的数量仍然停滞不前，5年总生存率估计为9%。新出现的证据表明，胃肠道内的微生物可以通过激活免疫系统影响癌症反应。在这项研究中，我们分析了胰腺癌长期幸存者和对照者的粪便微生物组。观察到了几种先前与增强肿瘤免疫反应相关的丰富菌种，包括Faecalibacter这些发现需要进一步的研究来评估粪便微生物群可能增强胰腺癌免疫反应的机制。
BackgroundThe 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.MethodsIn 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.ResultsAll 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 theRuminococacceaefamily specificallyFaecalibacterium prausnitziispecies as well asAkkermansia muciniphilaspecies.ConclusionsStool from patients cured from PCa has more relative abundance ofFaecalibacterium prausnitziiandAkkermansia muciniphila.Additional studies are needed to explore potential mechanisms by which the fecal microbiota may influence survival in PCa.Plain Language SummaryAlthough 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 includingFaecalibacterium prausnitziiandAkkermansia muciniphila.These findings warrant additional study assessing mechanisms by which the fecal microbiota may enhance pancreatic cancer immune response.