Abstract
Background
Colorectal cancer (CRC) screening and detecting it at an early stage is an effective way to decrease mortality from CRC. Colonoscopy, considered the gold standard (GS) for diagnosing the disease in many countries, has several limitations. Therefore, the main focus of this literature is to investigate the ability of combining candidate gut microbiota for early diagnosis of CRC, both in the presence and absence of GS test outcomes.
Methods
We analyzed the data derived from a case-control study, including 83 screening colonoscopies conducted on subjects aged 18–92 years in Tehran, Iran. The candidate gut microbiota including, ETBF, Enterococcus faecalis, and Porphyromonas gingivalis were quantified in samples using absolute qRT PCR. The Bayesian latent class model (LCM) was employed to combine the values from the multiple bacterial markers in order to optimize the discriminatory ability compared with a single marker.
Results
Based on Bayesian logistic regression, we discovered that family history of CRC, physical activity, cigarette smoking, and food diet were all significantly associated with an increased risk of CRC. When comparing ETBF and E. faecalis to P. gingivalis, we have observed that P. gingivalis exhibited greater predictive power in detecting high-risk individuals with CRC. As such, the sensitivity, specificity, and the area under the receiver-operating characteristics curve of combining ETBF, E. faecalis, and P. gingivalis were 98%, 96%, and 0.97, respectively.
Conclusions
This study suggests that the combined use of the three markers markedly improves classification performance compared to pairwise combinations, as well as individual markers, both with and without GS test outcomes. Noticeably, the triple composition of the fecal markers may serve as a reliable non-invasive indicator for the early prediction of CRC.
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Availability of Data and Materials
The datasets generated during and analyzed during the current study are not publicly available due to privacy of the study project but are available from the corresponding author on reasonable request.
Abbreviations
- CRC:
-
Colorectal cancer
- gFOBT:
-
Guaiac-based fecal occult blood test
- FIT:
-
Fecal immunochemical test
- GS:
-
Gold standard
- ETBF:
-
Enterotoxigenic Bacteroides fragilis
- P. gingivalis :
-
Porphyromonas gingivalis
- E. faecalis :
-
Enterococcus faecalis
- AUC:
-
Area under the curve
- LCM:
-
Latent class model
- ROC:
-
Receiver operating characteristic
- SD:
-
Standard deviation
- MCMC:
-
Markov chain Monte Carlo
- CrI:
-
Credible interval
- OR:
-
Odds ratio
References
Bujang N-N-A, Lee Y-J, Mohd-Zain S-A-S, Aris J-H, Md-Yusoff F-A, Suli Z, et al. Factors associated with colorectal cancer screening via immunochemical fecal occult blood test in an average-risk population from a multiethnic, middle-income setting. JCO Glob Oncol. 2021;7(1):333–41.
Jiang H, Guo W, Huang K, Jiang H, Zhang R, Hu H, et al. Screening of radiotracer for diagnosis of colorectal cancer liver metastasis based on MACC1-SPON2.Abdom Radiol. 2021;46(7):3227–37.
Wong MC, Huang J, Lok V, Wang J, Fung F, Ding H, et al. Differences in incidence and mortality trends of colorectal cancer worldwide based on sex, age, and anatomic location. Clin Gastroenterol Hepatol. 2021;19(5):955–66. e61.
Deo S, Kumar S, Bhoriwal S, Shukla N, Sharma A, Thulkar S, et al. Colorectal cancers in low-and middle-income countries—Demographic pattern and clinical profile of 970 patients treated at a tertiary care cancer center in India. JCO Global Oncol. 2021;7:1110–5.
Cao Y, Zhao G, Yuan M, Liu X, Ma Y, Cao Y, et al. KCNQ5 and C9orf50 methylation in stool DNA for early detection of colorectal cancer. Front Oncol. 2021;10: 621295.
Njor SH, Andersen B, Friis-Hansen L, de Haas N, Linnemann D, Nørgaard H, et al. The optimal cut-off value in fit-based colorectal cancer screening: An observational study. Cancer Med. 2021;10(5):1872–9.
Ramazani AA, Norozi E, AmirabadiZadeh H, Ehteshampour AR, Salehiniya H. Predictors of colorectal cancer screening participation in Southern Khorasan (Iran). J Gastrointest Cancer. 2021;52(1):187–91.
Wu X, Zhang Y, Hu T, He X, Zou Y, Deng Q, et al. A novel cell-free DNA methylation-based model improves the early detection of colorectal cancer. Mol Oncol. 2021;15(10):2702–14.
Villéger R, Lopès A, Veziant J, Gagnière J, Barnich N, Billard E, et al. Microbial markers in colorectal cancer detection and/or prognosis. World J Gastroenterol. 2018;24(22):2327.
Su W-C, Kao W-Y, Chang T-K, Tsai H-L, Huang C-W, Chen Y-C, et al. Stool DNA test targeting methylated syndecan-2 (SDC2) as a noninvasive screening method for colorectal cancer. Biosci Rep. 2021;41(1).
Wu Y, Yang X, Jiang G, Zhang H, Ge L, Chen F, et al. 5′-tRF-GlyGCC: A tRNA-derived small RNA as a novel biomarker for colorectal cancer diagnosis. Genome medicine. 2021;13(1):1–12.
Buturovic S. Colonoscopy as a method of choice in the diagnosis of colorectal cancer. Acta Informatica Medica. 2014;22(3):164.
Triantafillidis JK, Vagianos C, Malgarinos G. Colonoscopy in colorectal cancer screening: Current aspects. Indian J Surg Oncol. 2015;6:237–50.
Zhang W, Xiao G, Chen J, Wang L, Hu Q, Wu J, et al. Electrochemical biosensors for measurement of colorectal cancer biomarkers. Anal Bioanal Chem. 2021;413(9):2407–28.
Lee K, Seo H, Choe S, Jeong S-Y, Park JW, Suh M, et al. Intentions to undergo primary screening with colonoscopy under the National Cancer Screening Program in Korea. PLoS ONE. 2021;16(2):e0247252.
Pellino G, Gallo G, Pallante P, Capasso R, De Stefano A, Maretto I, et al. Noninvasive biomarkers of colorectal cancer: Role in diagnosis and personalised treatment perspectives. Gastroenterology Res Pract. 2018;2018.
Peterse EF, Meester RG, de Jonge L, Omidvari A-H, Alarid-Escudero F, Knudsen AB, et al. Comparing the cost-effectiveness of innovative colorectal cancer screening tests. JNCI: J Natl Cancer Inst. 2021;113(2):154–61.
Liu W, Zhang R, Shu R, Yu J, Li H, Long H, et al. Study of the relationship between microbiome and colorectal cancer susceptibility using 16SrRNA sequencing. BioMed Res Int. 2020;2020.
De Almeida CV, Lulli M, di Pilato V, Schiavone N, Russo E, Nannini G, et al. Differential responses of colorectal cancer cell lines to Enterococcus faecalis’ strains isolated from healthy donors and colorectal cancer patients. J Clin Med. 2019;8(3):388.
Zamani S, Taslimi R, Sarabi A, Jasemi S, Sechi LA, Feizabadi MM. Enterotoxigenic Bacteroides fragilis: A possible etiological candidate for bacterially-induced colorectal precancerous and cancerous lesions. Front Cell Infect Microbiol. 2020;9:449.
Bao Y, Tang J, Qian Y, Sun T, Chen H, Chen Z, et al. Long noncoding RNA BFAL1 mediates enterotoxigenic Bacteroides fragilis-related carcinogenesis in colorectal cancer via the RHEB/mTOR pathway. Cell Death Dis. 2019;10(9):1–14.
Lafuente Ibáñez de Mendoza I, Maritxalar Mendia X, Garcia de la Fuente AM, Quindos Andres G, Aguirre Urizar JM. Role of Porphyromonas gingivalis in oral squamous cell carcinoma development: A systematic review. J Periodontal Res. 2020;55(1):13–22.
Rodríguez IT, Ballart JF, Pastor GC, Jorda EB, Val VA. Validation of a short questionnaire on frequency of dietary intake: Reproducibility and validity. Nutr Hosp. 2008;23(3):242–52.
Rezasoltani S, Sharafkhah M, Aghdaei HA, Mojarad EN, Dabiri H, Sepahi AA, et al. Applying simple linear combination, multiple logistic and factor analysis methods for candidate fecal bacteria as novel biomarkers for early detection of adenomatous polyps and colon cancer. J Microbiol Methods. 2018;155:82–8.
Collins J, Albert PS. Estimating diagnostic accuracy without a gold standard: A continued controversy. J Biopharm Stat. 2016;26(6):1078–82.
Pereira GdA, Louzada F, Barbosa VdF, Ferreira-Silva MM, Moraes-Souza H. A general latent class model for performance evaluation of diagnostic tests in the absence of a gold standard: An application to Chagas disease. Comput Math Methods Med. 2012;2012.
Pepe MS, Janes H. Insights into latent class analysis of diagnostic test performance. Biostatistics. 2007;8(2):474–84.
Qin J, Zhang B. Best combination of multiple diagnostic tests for screening purposes. Stat Med. 2010;29(28):2905–19.
Yu B, Zhou C, Bandinelli S. Combining multiple continuous tests for the diagnosis of kidney impairment in the absence of a gold standard. Stat Med. 2011;30(14):1712–21.
Keku TO, Dulal S, Deveaux A, Jovov B, Han X. The gastrointestinal microbiota and colorectal cancer. Am J Physiol Gastrointest Liver Physiol. 2015;308(5):G351-G63.
Haghi F, Goli E, Mirzaei B, Zeighami H. The association between fecal enterotoxigenic B. fragilis with colorectal cancer. BMC Cancer. 2019;19(1):1–4.
Vacante M, Ciuni R, Basile F, Biondi A. Gut microbiota and colorectal cancer development: A closer look to the adenoma-carcinoma sequence. Biomedicines. 2020;8(11):489.
Khan Z, Siddiqui N, Saif MW. Enterococcus faecalis infective endocarditis and colorectal carcinoma: Case of new association gaining ground. Gastroenterology Res. 2018;11(3):238.
Liu X-b, Gao Z-y, Sun C-t, Wen H, Gao B, Li S-b, et al. The potential role of P. gingivalis in gastrointestinal cancer: A mini review. Infectious Agents and Cancer. 2019;14(1):1–7.
Kim M, Lee S-T, Choi S, Lee H, Kwon SS, Byun JH, et al. Fusobacterium nucleatum in biopsied tissues from colorectal cancer patients and alcohol consumption in Korea. Sci Rep. 2020;10(1):1–10.
Purcell RV, Pearson J, Aitchison A, Dixon L, Frizelle FA, Keenan JI. Colonization with enterotoxigenic Bacteroides fragilis is associated with early-stage colorectal neoplasia. PLoS ONE. 2017;12(2):e0171602.
Oyeyemi SO, Braaten T, Licaj I, Lund E, Benjaminsen BK. Physical activity patterns and the risk of colorectal cancer in the Norwegian Women and Cancer study: A population-based prospective study. BMC Cancer. 2018;18(1):1–11.
Luo W-P, Fang Y-J, Lu M-S, Zhong X, Chen Y-M, Zhang C-X. High consumption of vegetable and fruit colour groups is inversely associated with the risk of colorectal cancer: A case–control study. Br J Nutr. 2015;113(7):1129–38.
Morris JS, Bradbury KE, Cross AJ, Gunter MJ, Murphy N. Physical activity, sedentary behaviour and colorectal cancer risk in the UK Biobank. Br J Cancer. 2018;118(6):920–9.
Khatatbeh MM, Jadallah KA, Bashtawy MA, Hamaydeh SA, Gharaibeh MA, Kanaan NB, et al. Factors associated with colorectal cancer among Jordanians: A case-control study. Asian Pacific Journal of Cancer Prevention: APJCP. 2018;19(2):577.
Miles L. Physical activity and the prevention of cancer: A review of recent findings. Nutr Bull. 2007;32(3):250–82.
Zhou X-Y, Yan L, Wang L-L, Wang J. Association between physical activity and colorectal cancer risk and prognosis: A meta-analysis. Cancer Treat Res Commun. 2016;9:62–9.
Shaw E, Farris MS, Stone CR, Derksen JW, Johnson R, Hilsden RJ, et al. Effects of physical activity on colorectal cancer risk among family history and body mass index subgroups: A systematic review and meta-analysis. BMC Cancer. 2018;18(1):1–15.
Hannan LM, Jacobs EJ, Thun MJ. The association between cigarette smoking and risk of colorectal cancer in a large prospective cohort from the United States. Cancer Epidemiol Biomark Prev. 2009;18(12):3362–7.
Luchtenborg M, White KK, Wilkens L, Kolonel LN, Le Marchand L. Smoking and colorectal cancer: Different effects by type of cigarettes? Cancer Epidemiol Biomark Prev. 2007;16(7):1341–7.
Peppone LJ, Hyland A, Moysich KB, Reid ME, Piazza KM, Purnell JQ, et al. Examining the association between cigarette smoking and colorectal cancer using historical case–control data. Cancer Epidemiol. 2009;33(3–4):182–8.
Wei P-L, Lin S-Y, Chang Y-J. Cigarette smoking and colorectal cancer: From epidemiology to bench. J Exp Clin Med. 2011;3(6):257–61.
Lee S, Woo H, Lee J, Oh J-H, Kim J, Shin A. Cigarette smoking, alcohol consumption, and risk of colorectal cancer in South Korea: A case-control study. Alcohol. 2019;76:15–21.
Golshiri P, Rasooli S, Emami M, Najimi A. Effects of physical activity on risk of colorectal cancer: A case–control study. Int J Prev Med. 2016;7.
Bante SA, Getie SA, Getu AA, Mulatu K, Fenta SL. Uptake of pre-cervical cancer screening and associated factors among reproductive age women in Debre Markos town, Northwest Ethiopia, 2017. BMC Public Health. 2019;19(1):1–9.
van Smeden M, Naaktgeboren CA, Reitsma JB, Moons KG, de Groot JA. Latent class models in diagnostic studies when there is no reference standard—A systematic review. Am J Epidemiol. 2014;179(4):423–31.
Acknowledgements
The authors would like to express their gratitude to Gastroenterology and Liver Diseases Research Center of Shahid Beheshti University of Medical Sciences for the facilitation of the process to conduct this study.
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Conceptualization, methodology, software, formal analysis, investigation, resources, responsible for data, data curation, writing—original draft preparation, writing—review and editing, and supervision: MA. Data collection: SR and HAA. All authors reviewed and agreed to the published version of the manuscript.
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This work is based upon research funded by Iran National Science Foundation (INSF) under project No. 99019094. Written informed consent was obtained from each subject enrolled into the study. All methods were carried out in accordance with relevant guidelines and regulations. In addition, we confirm that the experimental protocol was approved by the clinical research ethics committee of the Shahid Beheshti University of Medical Sciences and the ethics committee of Taleghani Hospital in Tehran, Iran.
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Amini, M., Rezasoltani, S., Asadzadeh Aghdaei, H. et al. Accuracy of the Discriminatory Ability of Combined Fecal Microbiota Panel in the Early Detection of Patients with Colorectal Cancer. J Gastrointest Canc 55, 332–343 (2024). https://doi.org/10.1007/s12029-023-00962-z
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DOI: https://doi.org/10.1007/s12029-023-00962-z