Metagenomic analysis of metastatic colorectal cancer

In the latest issue of Molecular Oncology, Marongiu et al. investigated the microbiome of colorectal cancer tumours, their metastases and normal tissue to understand whether they could differentiate between these pathological stages using the bacterial and viral populations in their microbiome.

Like Comment

The human microbiome is a dynamic group of microbes that contribute, either positively or negatively, to our health and wellbeing. Different parts of the body host different microbial communities, so the microbiome of the skin will differ from that of the stomach or the lung. Recent studies have linked changes in the composition of the microbiome to numerous aspects of health and disease including how effective antibiotics are, and to the risk of developing neurological diseases such as Alzheimer’s [1]. Studies of the microbiome have also revealed possible links to carcinogenesis and cancer therapeutic responses in patients [2]. For example, recent studies have found certain types of bacteria from the gut microbiota can determine the antitumour effects of some immunotherapies [3]. It is therefore important to expand our understanding of the role of the microbiome in contributing to carcinogenesis, metastasis and therapy responses.

Metagenomics employs Next Generation Sequencing (NGS) technologies to sequence the DNA of the microbiome and then that information can be used to identify the microbial constituents by matching the DNA sequences to pre-sequenced genomes in databases. In the latest issue of Molecular Oncology Marongiu et al. [4] used metagenomics to collect information on whether there is any connection between the composition of the microbiome and the metastasis of colorectal cancer, which is one of the most prevalent cancers globally with a high mortality and increasing prevalence among young people.

To address this question, Marongiu et al. [4] compared the microbiome of colorectal cancer (CRC) primary tumours to that of their metastases and normal tissue.

The authors carried out sequencing of CRC primary tumours, their lung or liver metastases and normal tissue from twelve patients. Those DNA sequences were run through the Basic Local Alignment Software Tool (BLAST) which uses sequence similarity to identify the most likely species of origin. After further filtering of the sequences to avoid false-positives, there were 61 viral species and the authors found that bacteriophages (viruses that use bacteria as a host), RNA and DNA viruses were represented in all the samples. The authors focussed on the prevalence of Epstein-Barr virus (EBV), which is known to have some oncogenic potential, and found that EBV was present significantly more in CRC tumour samples than normal tissue, as also verified by using polymerase chain reaction (PCR). Next, the authors turned their attention to the bacterial composition of the microbiome. They found that 122 species were specific to CRC primary tumours. The authors were able to use this data and the viral data to discriminate between primary CRC tumours, their metastases and normal tissues using the Hutchinson’s t-test as a measure of the difference in microbial diversity between the samples and the Shannon indices which measures species richness and abundance.

Overall, while investigating the microbiome of CRC tumours, their lung and liver metastases and normal tissue, Marongiu et al. were able to statistically differentiate between pathological stages based on viral and bacterial signatures of the microbiome. Future work may attempt to further validate these findings within a larger study set. Ultimately, this study provides an important insight into the microbial changes that may occur during CRC carcinogenesis and metastasis which could be used to identify patients who may be at increased risk of CRC metastasis.

Poster image: Darryl Leja, NHGRI (https://www.flickr.com/photos/genomegov/30395469313)

 References

  1. Hill, J.M., Clement, C., Pogue, A.I., Bhattacharjee, S., Zhao, Y. and Lukiw, W.J., (2014) ‘Pathogenic microbes, the microbiome, and Alzheimer’s disease (AD)’, Frontiers in aging neuroscience6, p.127.
  2. Helmink, B.A., Khan, M.W., Hermann, A., Gopalakrishnan, V. and Wargo, J.A., (2019), ‘The microbiome, cancer, and cancer therapy’, Nature medicine25(3), pp.377-388.
  3. Sivan, A., Corrales, L., Hubert, N., Williams, J.B., Aquino-Michaels, K., Earley, Z.M., Benyamin, F.W., Lei, Y.M., Jabri, B., Alegre, M.L. and Chang, E.B., (2015), ‘Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy’ Science350(6264), pp.1084-1089
  4. Marongiu, L., Landry, J.J.M., Rausch, T., Abba, M.L., Delecluse, ., Delecluse, H.-J. and Allgayer, H. (2021), ‘Metagenomic analysis of primary colorectal carcinomas and their metastases identifies potential microbial risk factors’, Mol Oncol.

 

Molecular Oncology

Molecular Oncology is an Open Access international journal that highlights new discoveries, approaches, as well as technical developments, in basic, clinical and discovery-driven translational cancer research.