Analysis of microbial sequences in plasma cell-free DNA for early-onset breast cancer patients and healthy females
Open accessAbstract
BACKGROUND: Cell-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. RESULTS: The 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. CONCLUSIONS: Our 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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Blood-based microbial DNA can be clinically informative in cancer, including cancers with blood-barrier or lymphatic disruptions.
“There is mounting evidence that blood-based microbial DNA (hereafter “mbDNA”) can be clinically informative in cancer39–44, including those featuring blood-barrier or lymphatic disruptions (e.g. COAD)39”
From RETRACTED ARTICLE: Microbiome analyses of blood and tissues suggest cancer diagnostic approach (2020) · cites this paper as [44]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400 · see citing works
Quality control and preprocessing of metagenomic datasets
Schmieder, R., & Edwards, R. A. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr026 · Cited by 4,989 · see citing works
Coming of age: ten years of next-generation sequencing technologies
Goodwin, S., McPherson, J. D., & McCombie, W. R. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.49 · Cited by 4,352 · see citing works
The global health burden of infection‐associated cancers in the year 2002
Parkin, D. M. (2006) · International Journal of Cancer · doi:10.1002/ijc.21731 · Cited by 2,932 · see citing works
NGS QC Toolkit: A Toolkit for Quality Control of Next Generation Sequencing Data
Patel, R. K., & Jain, M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030619 · Cited by 2,921 · see citing works
Mechanisms of Human Papillomavirus-Induced Oncogenesis
Münger, K., Baldwin, A. E., Edwards, K. M., Hayakawa, H., Nguyen, C. L., Owens, M., Grace, M. R., & Huh, K.-W. (2004) · Journal of Virology · doi:10.1128/jvi.78.21.11451-11460.2004 · Cited by 1,050 · see citing works
Skin microbiota: a source of disease or defence?
Cogen, A. L., Nizet, V., & Gallo, R. L. (2008) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2008.08437.x · Cited by 954 · see citing works
Microbiota: a key orchestrator of cancer therapy
Roy, S., & Trinchieri, G. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.13 · Cited by 883 · see citing works
Microbial Dysbiosis Is Associated with Human Breast Cancer
Xuan, C., Shamonki, J. M., Chung, A., DiNome, M. L., Chung, M., Sieling, P. A., & Lee, D. J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0083744 · Cited by 543 · see citing works
Viruses associated with human cancer
McLaughlin-Drubin, M. E., & Münger, K. (2007) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2007.12.005 · Cited by 414 · see citing works
The dormant blood microbiome in chronic, inflammatory diseases
Potgieter, M., Bester, J., Kell, D. B., & Pretorius, E. (2015) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuv013 · Cited by 377 · see citing works
Viral carcinogenesis: revelation of molecular mechanisms and etiology of human disease
Butel, J. S. (2000) · Carcinogenesis · doi:10.1093/carcin/21.3.405 · Cited by 366 · see citing works
Next-generation sequencing diagnostics of bacteremia in septic patients
Grumaz, S., Stevens, P., Grumaz, C., Decker, S., Weigand, M. A., Hofer, S., Brenner, T., von Haeseler, A., & Sohn, K. (2016) · Genome Medicine · doi:10.1186/s13073-016-0326-8 · Cited by 347 · see citing works
Seifert, H., Dijkshoorn, L., Gerner‐Smidt, P., Pelzer, N., Tjernberg, I., & Vaneechoutte, M. (1997) · Journal of Clinical Microbiology · doi:10.1128/jcm.35.11.2819-2825.1997 · Cited by 321 · see citing works
Acinetobacter infection – an emerging threat to human health
Visca, P., Seifert, H., & Towner, K. J. (2011) · IUBMB Life · doi:10.1002/iub.534 · Cited by 319 · see citing works
Does Blood of Healthy Subjects Contain Bacterial Ribosomal DNA?
Nikkari, S., McLaughlin, I., Bi, W.-L., Dodge, D., & Relman, D. (2001) · Journal of Clinical Microbiology · doi:10.1128/jcm.39.5.1956-1959.2001 · Cited by 248 · see citing works
Dinakaran, V., Rathinavel, A., Muthuirulan, P., Sivakumar, R., Gunasekaran, P., & Rajendhran, J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0105221 · Cited by 196 · see citing works
Bacteria and tumours: causative agents or opportunistic inhabitants?
Cummins, J., & Tangney, M. (2013) · Infectious Agents and Cancer · doi:10.1186/1750-9378-8-11 · Cited by 178 · see citing works
Distribution of Acinetobacter Species on Skin of Healthy Humans
Aucken, H. M., Berlau, J., Malnick, H., & Pitt, T. L. (1999) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s100960050254 · Cited by 167 · see citing works
Bacteria-Human Somatic Cell Lateral Gene Transfer Is Enriched in Cancer Samples
Riley, D. R. J., Sieber, K. B., Robinson, K. M., White, J. R., Ganesan, A., Nourbakhsh, S., & Hotopp, J. C. D. (2013) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003107 · Cited by 163 · see citing works
Are There Naturally Occurring Pleomorphic Bacteria in the Blood of Healthy Humans?
McLaughlin, R. W., Vali, H., Lau, P. C. K., et al. (2002) · Journal of Clinical Microbiology · doi:10.1128/jcm.40.12.4771-4775.2002 · Cited by 123 · see citing works
de Oliveira, D. E. (2006) · Cancer Letters · doi:10.1016/j.canlet.2006.05.010 · Cited by 95 · see citing works
Guardabassi, L., Dalsgaard, A., & Olsen, J. E. (1999) · Journal of Applied Microbiology · doi:10.1046/j.1365-2672.1999.00905.x · Cited by 88 · see citing works
Buonaurio, R., Stravato, V. M., Kosako, Y., et al. (2002) · INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY · doi:10.1099/00207713-52-6-2081 · Cited by 73 · see citing works
Li, S.-K., Leung, R. K., Guo, H., Wei, J., Wang, J.-H., Kwong, K.-S., Lee, S.-S., Zhang, C., & Tsui, S. K. (2011) · Clinical Microbiology and Infection · doi:10.1111/j.1469-0691.2011.03690.x · Cited by 72 · see citing works
Understanding Microbe-Induced Cancers
Blaser, M. J. (2008) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-08-0024 · Cited by 60 · see citing works
Role of Helicobacter pylori Infection and Chronic Inflammation in Gastric Cancer in the Cardia
Egi, Y., Ito, M., Tanaka, S., Imagawa, S., Takata, S., Yoshihara, M., Haruma, K., & Chayama, K. (2007) · Japanese Journal of Clinical Oncology · doi:10.1093/jjco/hym029 · Cited by 31 · see citing works
[Identification and typing of Pseudomonas pickettii during an episode of nosocomial outbreak].
Hj, P., Teng, L., Ms, T., et al. (1992) · PubMed · Cited by 13 · see citing works
Tedeschi, G. G., Amici, D., Sprovieri, G., et al. (1976) · Cellular and Molecular Life Sciences · doi:10.1007/bf01924475 · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
RETRACTED ARTICLE: Microbiome analyses of blood and tissues suggest cancer diagnostic approach
Poore, G. D., Kopylova, E., Zhu, Q., Carpenter, C., Fraraccio, S., Wandro, S., Kosciolek, T., Janssen, S., Metcalf, J., Song, S. J., et al. (2020) · Nature · doi:10.1038/s41586-020-2095-1 · Cited by 989 · see citing works
RetractedSaid, S., & Ibrahim, W. (2025) · Cancer Management and Research · doi:10.2147/cmar.s405590 · Cited by 25 · see citing works
- Authors
- Huang, Y.-F., Chen, Y.-J., Fan, T.-C., Chang, N.-C., Chen, Y.-J., Midha, M. K., Chen, T.-H., Yang, H.-H., Wang, Y.-T., Yu, A. L., & Chiu, K.-P.
- Affiliations
- Genomics Research Center, Academia Sinica (TW)
- Chang Gung University (TW)
- National Taiwan University (TW)
- Corresponding author
- Chiu, Kuo-Ping
- Venue
- BMC Medical Genomics
- Published
- 2018-02
- Volume
- 11
- Issue
- S1
- Pages
- 16-16
- ISSN
- 1755-8794 (ISSN-L)
- PMC
- PMC5836824
- OpenAlex
- W2786496513
- Cited by
- 72
- References
- 29
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 10 · 2023: 13 · 2022: 7 · 2021: 5 · 2020: 14 · 2019: 3 · 2018: 1
- FWCI
- 1.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Medical Genomics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- Academia Sinica
- Genomics Research Center, Academia Sinica
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- microbial cell-free DNA, early-onset breast cancer, plasma cfDNA, microbial identification, Acinetobacter johnsonii, Pseudomonas mendocina, Pannonibacter phragmitetus, Sphingomonas, Mycobacterium, bacterial diversity, prognostic factors
- MeSH terms
- Cell-Free Nucleic Acids, Adult, Breast Neoplasms, DNA, Bacterial, Female, Humans, Prognosis, Biomarkers, Case-Control Studies, Age of Onset
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review