Abstract
Background: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Currently, colonoscopy remains the gold standard diagnostic test for CRC detection. Nonetheless, this technique is invasive and expensive. Remarkable ongoing strategies are focusing on the development of affordable methods to diagnose CRC at earlier stages. The introduction of suitable noninvasive, sensitive and specified diagnostic tests for early CRC detection by employing biomarker analysis seems to be a fundamental need to reduce the numbers of unnecessary colonoscopies. In this review, we provide an overview of single- and multi-panel biomarkers (Genomic markers, transcriptome markers, proteomic markers, inflammatory markers, and microbiome markers) encompassing noninvasive tests in blood and stool for early CRC detection.
Methods: A bibliographic search using PubMed/Medline, Web of Science, and EBSCOhost databases was performed to find relevant published studies over the last 6 years. Forty-three pertinent studies were included in this review.
Results: The primary outcome highlights the sensitivity and specificity of single diagnostic biomarkers studied in blood or stool. The secondary outcome reveals the sensitivity and specificity of the biomarkers panel (combinations) in blood or stool. While some markers show better performance, others are not suitable for screening purposes.
Conclusion: There is a need to adjust experimental and analytical tests that can interfere with a robust result to replace or supplement those markers that are currently in use. Nevertheless, robust verification and validation with large clinical cohorts are needed for successful noninvasive tests that can fulfill the role of colonoscopy.
Keywords: CRC, colonoscopy, noninvasive, markers, sensitivity, specificity, early detection.
Graphical Abstract
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[http://dx.doi.org/10.1186/s12916-015-0498-x] [PMID: 26459270]
[http://dx.doi.org/10.1186/s13148-017-0322-x] [PMID: 28270869]
[http://dx.doi.org/10.1371/journal.pmed.1000097] [PMID: 19621072]
[http://dx.doi.org/10.1007/s13258-017-0644-2] [PMID: 29892846]
[http://dx.doi.org/10.5217/ir.2017.15.4.495] [PMID: 29142517]
[http://dx.doi.org/10.3892/ol.2014.2815] [PMID: 25663916]
[http://dx.doi.org/10.1002/jgm.3189] [PMID: 32196834]
[http://dx.doi.org/10.1056/NEJMoa1311194]
[http://dx.doi.org/10.31557/APJCP.2019.20.10.2929] [PMID: 31653137]
[http://dx.doi.org/10.3748/wjg.v21.i9.2629] [PMID: 25759530]
[http://dx.doi.org/10.1016/j.cca.2020.01.010] [PMID: 31962098]
[http://dx.doi.org/10.1177/1724600818820536] [PMID: 30852954]
[http://dx.doi.org/10.1002/cam4.2475] [PMID: 31407497]
[http://dx.doi.org/10.1007/s00432-019-02992-2] [PMID: 31456088]
[http://dx.doi.org/10.1080/15592294.2017.1356957] [PMID: 28753106]
[http://dx.doi.org/10.1007/s00432-017-2363-0] [PMID: 28224298]
[http://dx.doi.org/10.3389/fonc.2018.00247] [PMID: 30013949]
[http://dx.doi.org/10.1186/s12885-019-5663-8] [PMID: 31088406]
[http://dx.doi.org/10.4103/japtr.JAPTR_381_18] [PMID: 31334094]
[http://dx.doi.org/10.4103/2277-9175.170677] [PMID: 26918234]
[http://dx.doi.org/10.1371/journal.pone.0180809] [PMID: 28700744]
[http://dx.doi.org/10.1371/journal.pone.0125041] [PMID: 25928810]
[http://dx.doi.org/10.1038/ctg.2015.67] [PMID: 26765125]
[http://dx.doi.org/10.1002/cncr.32695] [PMID: 31909823]
[http://dx.doi.org/10.1371/journal.pone.0099233] [PMID: 25025467]
[http://dx.doi.org/10.1186/s13148-019-0757-3] [PMID: 31727158]
[http://dx.doi.org/10.1590/S0004-28032015000400008] [PMID: 26840470]
[http://dx.doi.org/10.3389/fgene.2019.01096] [PMID: 31737058]
[http://dx.doi.org/10.3390/cancers12020341] [PMID: 32028703]
[http://dx.doi.org/10.1177/1533034615604797] [PMID: 26466603]
[http://dx.doi.org/10.1007/s13277-015-3967-0] [PMID: 26318304]
[http://dx.doi.org/10.1093/annonc/mdw279] [PMID: 27502702]
[http://dx.doi.org/10.1007/s13277-014-2760-9] [PMID: 25528214]
[PMID: 26261602]
[http://dx.doi.org/10.3389/fonc.2019.01129] [PMID: 31750241]
[http://dx.doi.org/10.3390/jcm8122029] [PMID: 31757017]
[http://dx.doi.org/10.1093/carcin/bgw078] [PMID: 27485599]
[http://dx.doi.org/10.1186/s13046-015-0198-6] [PMID: 26297223]
[http://dx.doi.org/10.1016/j.canep.2019.01.015] [PMID: 30925282]
[http://dx.doi.org/10.1186/s12967-019-1954-8] [PMID: 31221189]
[http://dx.doi.org/10.1016/j.clcc.2017.12.002] [PMID: 29352642]
[http://dx.doi.org/10.1155/2019/9852782] [PMID: 31467924]
[PMID: 28910954]
[http://dx.doi.org/10.1038/bjc.2015.202] [PMID: 26035703]
[http://dx.doi.org/10.1158/1078-0432.CCR-15-1268] [PMID: 26561557]
[http://dx.doi.org/10.1002/ijc.30558] [PMID: 27935033]
[http://dx.doi.org/10.1007/s12672-019-00364-3] [PMID: 31093954]
[http://dx.doi.org/10.1002/jcp.26936] [PMID: 30078189]
[PMID: 2030094]
[http://dx.doi.org/10.5009/gnl.2014.8.2.117] [PMID: 24672652]
[http://dx.doi.org/10.1080/00365521.2016.1228120] [PMID: 27623716]
[http://dx.doi.org/10.1016/j.ejca.2019.11.021] [PMID: 31972396]
[http://dx.doi.org/10.18632/oncotarget.15279] [PMID: 28206963]
[http://dx.doi.org/10.1097/MD.0000000000002502] [PMID: 26765465]
[http://dx.doi.org/10.1371/journal.pone.0131616] [PMID: 26158845]
[http://dx.doi.org/10.1038/bjc.2016.31] [PMID: 26908323]
[http://dx.doi.org/10.1002/ijc.32137] [PMID: 30653264]
[http://dx.doi.org/10.1371/journal.pone.0123484] [PMID: 25856316]
[http://dx.doi.org/10.1186/s12967-019-2008-y] [PMID: 31387598]
[PMID: 25932198]
[http://dx.doi.org/10.3390/cancers11081157] [PMID: 31409016]
[http://dx.doi.org/10.7150/thno.42507] [PMID: 32194852]
[http://dx.doi.org/10.1136/gutjnl-2016-312766] [PMID: 27797940]
[http://dx.doi.org/10.1016/j.mimet.2018.11.007] [PMID: 30439465]
[http://dx.doi.org/10.1155/2019/9841295] [PMID: 31827515]
[http://dx.doi.org/10.1093/mutage/gez022] [PMID: 31424514]
[http://dx.doi.org/10.1136/gutjnl-2014-309086] [PMID: 26041752]
[http://dx.doi.org/10.1136/bmj.g2467] [PMID: 24922745]
[http://dx.doi.org/10.1038/ajg.2010.179] [PMID: 20502450]
[PMID: 30746161]
[http://dx.doi.org/10.1097/PPO.0000000000000190] [PMID: 27341592]
[http://dx.doi.org/10.12998/wjcc.v6.i15.869] [PMID: 30568941]
[http://dx.doi.org/10.1155/2019/2673543] [PMID: 30944663]
[http://dx.doi.org/10.1177/1073274819862784] [PMID: 31431043]