Thompson Kevin J, Ingle James N, Tang Xiaojia, Chia Nicholas, Jeraldo Patricio R, Walther-Antonio Marina R, Kandimalla Karunya K, Johnson Stephen, Yao Janet Z, Harrington Sean C, Suman Vera J, Wang Liewei, Weinshilboum Richard L, Boughey Judy C, Kocher Jean-Pierre, Nelson Heidi, Goetz Matthew P, Kalari Krishna R
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America.
Department of Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, United States of America.
PLoS One. 2017 Nov 30;12(11):e0188873. doi: 10.1371/journal.pone.0188873. eCollection 2017.
The inflammatory tumoral-immune response alters the physiology of the tumor microenvironment, which may attenuate genomic instability. In addition to inducing inflammatory immune responses, several pathogenic bacteria produce genotoxins. However the extent of microbial contribution to the tumor microenvironment biology remains unknown. We utilized The Cancer Genome Atlas, (TCGA) breast cancer data to perform a novel experiment utilizing unmapped and mapped RNA sequencing read evidence to minimize laboratory costs and effort. Our objective was to characterize the microbiota and associate the microbiota with the tumor expression profiles, for 668 breast tumor tissues and 72 non-cancerous adjacent tissues. The prominent presence of Proteobacteria was increased in the tumor tissues and conversely Actinobacteria abundance increase in non-cancerous adjacent tissues. Further, geneset enrichment suggests Listeria spp to be associated with the expression profiles of genes involved with epithelial to mesenchymal transitions. Moreover, evidence suggests H. influenza may reside in the surrounding stromal material and was significantly associated with the proliferative pathways: G2M checkpoint, E2F transcription factors, and mitotic spindle assembly. In summary, further unraveling this complicated interplay should enable us to better diagnose and treat breast cancer patients.
炎症性肿瘤免疫反应会改变肿瘤微环境的生理状态,这可能会减弱基因组不稳定性。除了诱导炎症免疫反应外,几种病原菌还会产生基因毒素。然而,微生物对肿瘤微环境生物学的贡献程度仍然未知。我们利用癌症基因组图谱(TCGA)的乳腺癌数据,通过未映射和映射的RNA测序读取证据进行了一项新实验,以尽量减少实验室成本和工作量。我们的目标是对668个乳腺肿瘤组织和72个非癌性邻近组织的微生物群进行表征,并将微生物群与肿瘤表达谱相关联。肿瘤组织中变形菌门的显著存在增加,相反,非癌性邻近组织中放线菌的丰度增加。此外,基因集富集表明李斯特菌属与上皮-间质转化相关基因的表达谱有关。此外,有证据表明流感嗜血杆菌可能存在于周围的基质材料中,并且与增殖途径显著相关:G2M检查点、E2F转录因子和有丝分裂纺锤体组装。总之,进一步揭示这种复杂的相互作用将使我们能够更好地诊断和治疗乳腺癌患者。