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Evaluation of combined detection of multigene mutation and SDC2/SFRP2 methylation in stool specimens for colorectal cancer early diagnosis

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Abstract

Purpose

Molecular diagnostics of colorectal cancer (CRC) can be used as an auxiliary approach for patients recommended for colonoscopy, providing more CRC supplemental diagnosis options. This study investigated whether combined detection of KRAS/BRAF/APC mutation and SDC2/SFRP2 methylation can serve as auxiliary diagnostics in clinical management.

Methods

KRAS/BRAF/APC mutation and SDC2/SFRP2 methylation in stool samples from healthy donors, patients with CRC, advanced adenoma (AA), non-advanced adenoma (NAA), or other gastroenterological diseases were evaluated using quantitative PCR (qPCR) or methylation-specific quantitative PCR (MSP). Test accuracy was determined by evaluating the tests’ sensitivity, specificity, positive/negative predictive value (PPV/NPV), or positive/negative likelihood ratio (PLR/NLR).

Results

The combined fecal KRAS/BRAF/APC mutation and SFRP2/SDC2 methylation detection test achieved a sensitivity of 88.57% with a PPV of 93.64% and a PLR of 7.10 for CRC patients. In comparison, the corresponding parameters for multigene mutation were 46.67%, 92.59%, and 36.26 and 83.81%, 93.94%, and 7.47, for DNA methylation, separately. The sensitivity of the combined test, gene mutation test, and DNA methylation test approach was 75%, 28.26%, and 72.83%. Furthermore, the specificity of this approach in the NAA group was 79.49%. Meanwhile, the overall diagnostic specificity for the combined test in NAA, healthy control, and interference groups was 88.42%. In addition, the sensitivity of the combined detection method increased with the disease stage in CRC patients and elevated along with the lesion size (≥ 1 cm) in AA patients.

Conclusion

Combined detection of fecal KRAS/BRAF/APC mutation and SFRP2/SDC2 methylation has potential application value for the auxiliary diagnosis of CRC and AA.

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References

  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359-386. https://doi.org/10.1002/ijc.29210

    Article  CAS  PubMed  Google Scholar 

  2. Zhang S, Sun K, Zheng R, Zeng H, Wang S, Chen R, Wei W, He J (2021) Cancer incidence and mortality in China, 2015. JNCC 1:2–11

    Article  CAS  Google Scholar 

  3. Liu ZC, Zhehuan L, Yang Z, Tong Z, Jingying Z, Weicheng Y, Kaifeng P, Li WQ (2021) Interpretation of 2020 global cancer statistical report. Electronic Journal of Comprehensive Cancer Treatment 7:1–14

    Google Scholar 

  4. Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB (2019) Colorectal cancer. Lancet 394:1467–1480. https://doi.org/10.1016/s0140-6736(19)32319-0

    Article  PubMed  Google Scholar 

  5. Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RGS, Barzi A, Jemal A (2017) Colorectal cancer statistics, 2017. CA Cancer J Clin 67:177–193. https://doi.org/10.3322/caac.21395

    Article  PubMed  Google Scholar 

  6. Hundt S, Haug U, Brenner H (2009) Comparative evaluation of immunochemical fecal occult blood tests for colorectal adenoma detection. Ann Intern Med 150:162–169. https://doi.org/10.7326/0003-4819-150-3-200902030-00005

    Article  PubMed  Google Scholar 

  7. Chen H, Li N, Ren J, Feng X, Lyu Z, Wei L, Li X, Guo L, Zheng Z, Zou S, Zhang Y, Li J, Zhang K, Chen W, Dai M, He J (2019) Participation and yield of a population-based colorectal cancer screening programme in China. Gut 68:1450–1457. https://doi.org/10.1136/gutjnl-2018-317124

    Article  PubMed  Google Scholar 

  8. Jenkinson F, Steele R (2010) Colorectal cancer screening–methodology. Surgeon 8:164–171

    Article  CAS  Google Scholar 

  9. Haug U, Hundt S, Brenner H (2010) Quantitative immunochemical fecal occult blood testing for colorectal adenoma detection: evaluation in the target population of screening and comparison with qualitative tests. Am J Gastroenterol 105:682–690. https://doi.org/10.1038/ajg.2009.668

    Article  PubMed  Google Scholar 

  10. Lee JK, Liles EG, Bent S, Levin TR, Corley DA (2014) Accuracy of fecal immunochemical tests for colorectal cancer: systematic review and meta-analysis. Ann Intern Med 160:171. https://doi.org/10.7326/m13-1484

    Article  PubMed  PubMed Central  Google Scholar 

  11. Schoen RE, Pinsky PF, Weissfeld JL, Yokochi LA, Church T, Laiyemo AO, Bresalier R, Andriole GL, Buys SS, Crawford ED, Fouad MN, Isaacs C, Johnson CC, Reding DJ, O’Brien B, Carrick DM, Wright P, Riley TL, Purdue MP, Izmirlian G, Kramer BS, Miller AB, Gohagan JK, Prorok PC, Berg CD (2012) Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med 366:2345–2357. https://doi.org/10.1056/NEJMoa1114635

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Chinese Anti Cancer Association (2018) Expert consensus on early diagnosis and screening strategy of colorectal cancer in China. Chin J Gastrointest Surg 21:1081–1086

  13. Kisiel JB, Limburg PJ (2020) Colorectal cancer screening with the multitarget stool DNA test. Am J Gastroenterol 115:1737–1740. https://doi.org/10.14309/ajg.0000000000000968

    Article  PubMed  Google Scholar 

  14. Kisiel JB, Eckmann JD, Limburg PJ (2020) Multitarget stool DNA for average risk colorectal cancer screening: major achievements and future directions. Gastrointest Endosc Clin N Am 30:553–568. https://doi.org/10.1016/j.giec.2020.02.008

    Article  PubMed  Google Scholar 

  15. Imperiale TF, Ransohoff DF, Itzkowitz SH, Levin TR, Lavin P, Lidgard GP, Ahlquist DA, Berger BM (2014) Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med 370:1287–1297. https://doi.org/10.1056/NEJMoa1311194

    Article  CAS  PubMed  Google Scholar 

  16. Oh TJ, Oh HI, Seo YY, Jeong D, Kim C, Kang HW, Han YD, Chung HC, Kim NK, An S (2017) Feasibility of quantifying SDC2 methylation in stool DNA for early detection of colorectal cancer. Clin Epigenetics 9:126. https://doi.org/10.1186/s13148-017-0426-3

    Article  PubMed  PubMed Central  Google Scholar 

  17. Shao S-X, Shen Z, Zhang X-F, Wang D, Wang H (2020) Application of multiple-gene stool DNA test in screening for early colorectal cancer. Chinese Journal of General Practice 18:1819–1822. https://doi.org/10.16766/j.cnki.issn.1674-4152.001627

    Article  Google Scholar 

  18. Bosch LJ, Carvalho B, Fijneman RJ, Jimenez CR, Pinedo HM, van Engeland M, Meijer GA (2011) Molecular tests for colorectal cancer screening. Clin Colorectal Cancer 10:8–23. https://doi.org/10.3816/CCC.2011.n.002

    Article  CAS  PubMed  Google Scholar 

  19. Liu C, Xu L, Li W, Jie M, Xue W, Yu W (2021) Multiple biomarker-combined screening for colorectal cancer based on bisulfate conversion-free detection of fecal DNA methylation. Biomed Res Int 2021:1479748. https://doi.org/10.1155/2021/1479748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Sidransky D, Tokino T, Hamilton SR, Kinzler KW, Levin B, Frost P, Vogelstein B (1992) Identification of ras oncogene mutations in the stool of patients with curable colorectal tumors. Science 256:102–105. https://doi.org/10.1126/science.1566048

    Article  CAS  PubMed  Google Scholar 

  21. Imperiale TF, Ransohoff DF, Itzkowitz SH, Turnbull BA, Ross ME (2004) Fecal DNA versus fecal occult blood for colorectal-cancer screening in an average-risk population. N Engl J Med 351:2704–2714. https://doi.org/10.1056/NEJMoa033403

    Article  CAS  PubMed  Google Scholar 

  22. Gachabayov M, Lebovics E, Rojas A, Felsenreich DM, Latifi R, Bergamaschi R (2021) Performance evaluation of stool DNA methylation tests in colorectal cancer screening: a systematic review and meta-analysis. Colorectal Dis 23:1030–1042. https://doi.org/10.1111/codi.15521

    Article  CAS  PubMed  Google Scholar 

  23. Mo S, Wang H, Han L, Xiang W, Dai W, Zhao P, Pei F, Su Z, Ma C, Li Q, Wang Z, Cai S, Wang H, Liu R, Cai G (2021) Fecal multidimensional assay for non-invasive detection of colorectal cancer: fecal immunochemical test, stool DNA mutation, methylation, and intestinal bacteria analysis. Front Oncol 11:643136. https://doi.org/10.3389/fonc.2021.643136

    Article  PubMed  PubMed Central  Google Scholar 

  24. van Loon K, Huijbers EJM, Griffioen AW (2021) Secreted frizzled-related protein 2: a key player in noncanonical Wnt signaling and tumor angiogenesis. Cancer Metastasis Rev 40:191–203. https://doi.org/10.1007/s10555-020-09941-3

    Article  CAS  PubMed  Google Scholar 

  25. Müller HM, Oberwalder M, Fiegl H, Morandell M, Goebel G, Zitt M, Mühlthaler M, Ofner D, Margreiter R, Widschwendter M (2004) Methylation changes in faecal DNA: a marker for colorectal cancer screening? Lancet 363:1283–1285. https://doi.org/10.1016/s0140-6736(04)16002-9

    Article  PubMed  Google Scholar 

  26. Niu F, Wen J, Fu X, Li C, Zhao R, Wu S, Yu H, Liu X, Zhao X, Liu S, Wang X, Wang J, Zou H (2017) Stool DNA test of methylated syndecan-2 for the early detection of colorectal neoplasia. Cancer Epidemiol Biomarkers Prev 26:1411–1419. https://doi.org/10.1158/1055-9965.epi-17-0153

    Article  CAS  PubMed  Google Scholar 

  27. Xu G, Chenxi M, Wei W (2021) Application of multitarget fecal FIT-DNA detection technology in screening colorectal cancer patients, spouses and first-degree relatives. Chinese Electronic Journal of Colorectal Diseases 10:237–242

    Google Scholar 

Download references

Funding

This study is supported by the Natural Science Foundation of Fujian Province, China (Grant No. 2021J01367).

Author information

Authors and Affiliations

  1. Department of Pathology, Fujian Provincial Hospital, Fuzhou, 350001, China

    Jie Lin & Yijuan Wu

  2. Department of Gastroenterology, Fujian Provincial Hospital, Fuzhou, 350001, China

    Lijing Zhang, Mengshi Chen, Juan Chen & Minghong Chen

  3. The Shengli Clinical Medical College, Fujian Medical University, No.134 East Street Fuzhou, Fuzhou, 350001, China

    Jie Lin, Lijing Zhang, Mengshi Chen, Juan Chen, Yijuan Wu & Minghong Chen

  4. Jiangsu Microdiag Biomedical Technology Co., LTD, Shanghai, China

    Tao Wang, Yan Lu, Zhaofen Ba, Xiaowei Cheng, Rongrong Xu, Tian Tian, Aijuan Sun & Tiantian Zhang

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  1. Jie Lin
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  2. Lijing Zhang
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  3. Mengshi Chen
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  4. Juan Chen
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  11. Tian Tian
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Corresponding author

Correspondence to Minghong Chen.

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Ethical approval

The Ethics committee of the Fujian Provincial Hospital approved the study (Ethics approval No. K2019-11–027).

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Written informed consent for participation was obtained from all subjects.

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The authors declare no competing interests.

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Lin, J., Zhang, L., Chen, M. et al. Evaluation of combined detection of multigene mutation and SDC2/SFRP2 methylation in stool specimens for colorectal cancer early diagnosis. Int J Colorectal Dis 37, 1231–1238 (2022). https://doi.org/10.1007/s00384-022-04170-2

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  • DOI: https://doi.org/10.1007/s00384-022-04170-2

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