Abstract
BackgroundCell-free circulating DNA (cfDNA) is becoming a useful biopsy for noninvasive diagnosis of diseases. Microbial sequences in plasma cfDNA may provide important information to improve prognosis and treatment. We have developed a stringent method to identify microbial species via microbial cfDNA in the blood plasma of early-onset breast cancer (EOBC) patients and healthy females. Empirically, microbe-originated sequence reads were identified by mapping non-human PE reads in cfDNA libraries to microbial databases. Those mapped concordantly to unique microbial species were assembled into contigs, which were subsequently aligned to the same databases. Microbial species uniquely aligned were identified and compared across all individuals on MCRPM (Microbial CfDNA Reads Per Million quality PE reads) basis.ResultsThe predominant microbial cfDNAs in all plasma samples examined are originated from bacteria and these bacteria were limited to only a few genera. Among those, Acinetobacter johnsonii XBB1 and low levels of Mycobacterium spp. were commonly found in all healthy females, but also present in an EOBC patient. Compared to those in healthy counterparts, bacterial species in EOBC patients are more diverse and more likely to present at high levels. Among these three EOBC patients tested, a patient who has record high titer (2,724 MCRPM) of Pseudomonas mendocina together with 8.82 MCRPM of Pannonibacter phragmitetus has passed away; another patient infected by multiple Sphingomonas species remains alive; while the third patient who has similar microbial species (Acinetobacter johnsonii XBB1) commonly seen in normal controls is having a normal life.ConclusionsOur preliminary data on the profiles of microbial cfDNA sequences suggested that it may have some prognostic value in cancer patients. Validation in larger number of patients is warranted.
Highlights
Cell-free circulating DNA is becoming a useful biopsy for noninvasive diagnosis of diseases
Microbial databases Genomic sequences of bacteria, fungi and viruses were downloaded from NCBI (April 6, 2017)
Library statistics Five plasma DNA libraries including BBC, EJC, BC0145 (EOBC), BC0190 (EOBC) and CGBC025 (EOBC) were sequenced by Illumina HiSeq X Ten to produce at least 384 million PE reads per library (Table 2)
Summary
Cell-free circulating DNA (cfDNA) is becoming a useful biopsy for noninvasive diagnosis of diseases. Microbe-originated sequence reads were identified by mapping non-human PE reads in cfDNA libraries to microbial databases Those mapped concordantly to unique microbial species were assembled into contigs, which were subsequently aligned to the same databases. Data have shown that these microbes may regulate a broad range of host physiological activities including metabolism, inflammation, immunity and hematopoiesis, which may in turn influence tumorigenesis and/or cancer development [9]. These data suggest that microbiota may play a key role to orchestrate cancer therapy and many more cancer-associated microbes need to be identified. Bacteria and fungi have complex genomes and their interactions with hosts are more intricate than that of viruses, making it more difficult to justify their roles in tumorigenesis [18]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
