Abstract
Background
Colorectal cancer (CRC) is a global health problem. The gut microbiome is now recognized as an important underlying factor to the initiation and progression of CRC. Fusobacterium nucleatum (FN) is one of the most studied bacteria in the aetiology of CRC. This study provided cohort evidence on the association of FN infection with clinicopathologic features in CRC patients.
Methods
We analysed the cancerous and adjacent non-cancerous formalin-fixed paraffin embedded (FFPE) tissue of 83 CRC patients from a single medical centre in Malaysia. TaqMan probe-based qPCR targeting the 16S rRNA gene was used to detect the presence of FN in the extracted FFPE DNA. The differences in FN expression between cancer and non-cancer tissues were evaluated. Association studies between FN infection in the tumour and relative FN abundance with available clinical data were conducted.
Results
FN was more abundant in the cancerous tissue compared to non-cancerous tissue (p = 0.0025). FN infection in the tumour was significantly associated with lymph node metastasis (p = 0.047) and cancer staging (p = 0.032), but not with other clinicopathologic variables. In double-positive patients where FN was detected in both cancerous and non-cancerous tissue, the expression fold-change of FN, calculated using 2-ΔΔCT formula, was significantly higher in patients with tumour size equal to or greater than 5 cm (p = 0.033) and in KRAS-mutated patients (p = 0.046).
Conclusions
FN is enriched in CRC tumour tissue and is associated with tumour size, lymph node metastasis, cancer staging, and KRAS mutation in this single-centre small cohort study.
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Data availability
All data supporting the findings of this study are available within the paper.
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Acknowledgements
S-W Pang is the recipient of Sunway University Postgraduate’s Degree by Research Studentship. We also thank Wenzhou-Kean University for continuously supporting the research work.
Funding
This research was funded by Sunway University Internal Grant 2020 (GRTIN-RSF-SHMS-DMS-03-2020) and partly supported by Sunway Medical Centre Research Fund (SRC/002/2017/FR and SRC/003/2017/FR).
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Material preparation and data collection were performed by SWP. The first draft of the manuscript was written by SWP. SCP and SYT edited the manuscript. All authors reviewed and edited the manuscript.
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This study was performed in line with the principles of the Declaration of Helsinki. Ethical approval for this study was granted from Sunway University Research Ethics Committee (PGSUREC 2018/052) and Sunway Medical Centre Independent Research Ethics Committee (013/2017/ER). Archived FFPE tissue blocks of CRC patients from year 2013 to 2015 were used in this project. The written informed consent was waived with the approval of the Institutional Review Board (IRB).
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Pang, SW., Armon, S., Chook, J. et al. Association of Fusobacterium nucleatum infection with the clinicopathological characteristics in colorectal cancer patients. Mol Biol Rep 51, 124 (2024). https://doi.org/10.1007/s11033-023-09150-5
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DOI: https://doi.org/10.1007/s11033-023-09150-5