Copyright ©The Author(s) 2021.
World J Gastrointest Oncol. Jul 15, 2021; 13(7): 638-661
Published online Jul 15, 2021. doi: 10.4251/wjgo.v13.i7.638
Table 1 Diagnostic biomarkers found in colorectal cancer
Diagnostic biomarker
Molecular level
Actin Beta-Like 2ProteinFresh frozen tissueGhazanfar et al[30], 2017
Dipeptidase 1ProteinFresh frozen tissueHao et al[31], 2017
Olfamectomedin-4 ProteinFFPE tissueQuesada-Calvo et al[32], 2017
Transport Protein Sec-24
Cyclophilin AProteinFFPE tissueYamamoto et al[33], 2016
Annexin A2
Aldolase A
Leucine-Rich Alpha-2 Glycoprotein 1 ProteinSerumIvancic et al[36], 2020
Epidermal Growth Factor Receptor
Superoxide Dismutase 3
Inter-Alpha-Trypsin Inhibitor Heavy-Chain Family Member 4
Mannan Binding Lectin Serine Protease 1 ProteinPlasma-Bhardwaj et al[37], 2019
Serum Paraoxonase Lactonase 3
Transferrin Receptor Protein 1
AdipophilinProteinPlasma-Matsubara et al[41], 2011
Caldesmon 1ProteinFresh Frozen Tissue-Ilyas et al[34], 2020
Catenin Beta 1
C-X-C Motif Chemokine Ligand 14
Protein patched homolog 1
Interleukin-8, Tumor necrosis factor-alpha induced protein 3, Nicotinamide N-methyltransferase
Mitogen-activated protein kinase
Adenomatous polyposis coli
Zinc finger protein
Serine/Threonine Kinase 4 ProteinSerumYu et al[38], 2017
Macrophage mannose receptor 1 ProteinFan et al[39], 2016
S100 calcium binding protein
Alpha-1-antitrypsin ProteinSerumPeltier et al[40], 2016
Anti- Thombin 3 ProteinSerumPeltier et al[40], 2016
3- Hydroxybutyric Acid SerumMa et al[43], 2012
Microtubule Actin Crosslinking Factor 1 ProteinSerumMa et al[43], 2012
L-Valine Amino acidSerumMa et al[43], 2012
Apolipoprotein H ProteinSerumMa et al[43], 2012
Immunoglobulin Lambda Locus
Vitamin-D-binding protein
Acetoacetate, GuanidinoacetateAmino acidUrine↑/HighWang et al[48], 2017
Cis-aconitate, Trans-aconitate, Glutamine
Creatinine, PhosphorylcholineAmino acidUrine↓/LowWang et al[48], 2017
Dimethyl sulfone, Asparagine, Alanine
Isocitrate, Hippurate, Methylamine
Cysteine, Phenylalanine
Isoleucine, β-Hydroxybutyrate, lactate, acetate, glutamate, choline, glycine, serine, glucose Amino acidBiopsyHighNishiumi et al[46], 2012
Taurine, alanine, β –Aminoisobutyrate, valine Amino acidUrineHighKim et al[47], 2019
Threonine, glycerol, hippurate, ascorbate, creatinine and citrateAmino acidUrineLessKim et al[47], 2019
Proline, succinate, isoleucine, leucine valine, alanine, glutamate, dimethylglycine and lactateAmino acidFecalHighLin et al[44], 2019
Short Chain Fatty Acids, (acetate, propionate and butyrate), glucose, glutamine Amino acidFecalLessLin et al[44], 2019
Sphinganine, endocannabinoids SerumHighMartín-Blázquez et al[51], 2019
CRCAL-4, CRCAL-3, CRCAL-2 (Long Intergenic Non-Protein Coding RNA 858), and CRCAL-1lncRNACRC cell lineYamada et al[27], 2018
NONHSAT074176.2lncRNAFresh frozen tissueZhang et al[28], 2018
CircDDX17lncRNAFresh frozen tissueDysregylatedLi et al[29], 2018
Syndecan 2GeneFresh frozen tissueOh et al[20], 2013
PHOX1B, Glutamic acid de-carboxylase 2, and Fibroblast Growth Factor 12GeneFresh frozen tissueLi et al[21], 2012
Visual System Homeobox 2GeneNeoplastic colonic tissueMori et al[22], 2011
Table 2 Prognostic markers found in colorectal cancer
Prognostic biomarker
Molecular level
Carcinoembryonic antigen ProteinPlasmaLi et al[79], 2018
Major histocompatibility complex, class I, B (HLAB)ProteinFresh Frozen TissueKirana et al[80], 2019
14-3-3b protein (YWHAB)
A disintegrin and metalloproteinase with thrombospondin motifs 2
Leukotriene B3
Nucleoside Diphosphate Kinase 2
Jagged Canonical Notch Ligand 2
Collagen type XII (FACIT)ProteinColorectal liver metastasis tissuevan Huizen et al[81], 2019
Heat shock protein 47ProteinFresh Frozen TissueMori et al[82], 2017
Ezrin proteinProteinCells and tissuePatara et al[85], 2011
Collagen VI (COL6)ProteinFresh Frozen TissueClarke et al[86], 2017
Forkhead box O3
RAD51 (DNA repair protein RAD51 homolog 1)
Lymphocyte-specific protein tyrosine kinase
Inositol polyphosphate-4-phosphatase
Phospho-PEA15 (Ser116)
Phosho-S6 (Ser240-244)
Phospho-PRAS40 (Thr-246)
Mammary serine protease inhibitor ProteinFresh Frozen TissueSnoeren et al[87], 2013
Alpha-fetoproteinProteinSerum-Zhu et al[88], 2013
Complement C4-A (C4A)
Fibrinogen alpha
Eukaryotic peptide chain release factor GTP-binding subunit ERF3B (GSPT2)
Hippurate, ButyrateAmino acidUrineLiesenfeld et al[89], 2015
Glycerol, Galactarate
Urea, CarnitineAmino acidUrineLiesenfeld et al[89], 2015
AFAP1 Antisense RNA 1lncRNADatasetsLi et al[72], 2016
Breast Cancer Anti-Estrogen Resistance 4
HOXA Cluster Antisense RNA 2
Metastasis Associated
Lung Adenocarcinoma Transcript 1 (MALAT1)
Plasmacytoma Variant Translocation 1
ADAMTS9 Antisense RNA 2 lncRNADatasetsLi et al[72], 2016
miR-429microRNAFresh Frozen TissueLi et al[73], 2013
hsa-mir-191, hsa-mir-200bmicroRNADatasets-Kandimalla et al[75], 2018
hsa-mir-30b, hsa-mir-30c2
hsa-mir-33a, hsamir-362
hsa-mir 429, and hsa-mir-744
VNN1-ABTranscriptDatasets-Løvf et al[76], 2014
Kirsten rat sarcoma oncogene 2 (KRAS)GeneDatasets-Kadowaki et al[67], 2015
Murine sarcoma viral oncogene homolog B1 (BRAF)
Tumor protein 53GeneDatasets-Ting et al[59], 2013
SMAD Family Member 4GeneDatasets-Mei et al[65], 2018
Neurofibromatosis type 1
Table 3 Drug repurposing candidates for the prevention and/or treatment of colorectal cancer
Drug (s)
Pharmacological class
Original indication
CRC effect
Based on computational approaches
GW-8510, ethacrynic acid, ginkgolide A and 6-azathymineGW-8510: Inhibitor of cyclin-dependent kinase-2; ethacrynic acid: Diuretic; ginkgolide A: Platelet-activating factor antagonist; 6-azathymine: D-3-aminoisobutyrate-pyruvate aminotransferase inhibitorGW-8510: Prevention of chemotherapy-induced alopecia; ethacrynic acid: Treatment of high blood pressure and swelling; ginkgolide A: Treatment of a wide variety of cognitive and vascular disordersInhibit CRC cellsChung et al[97], 2014
6-azathymine: Has antibacterial and antiviral activities
GW-8510Inhibitor of cyclin-dependent kinase-2Prevention of chemotherapy-induced alopeciaCRC therapeutic agent which targets RRM2 inhibitionHsieh et al[98], 2016
AbemaciclibAnti-neoplasticTreatment of advanced or metastatic breast cancersCRC therapeutic agent which targets FABP6Liñares-Blanco et al[99], 2020
AG 957, Ro-28-1675, Brazilin, Importazole, PD 407824AG 957: Inhibitor; Ro-28-1675: Activator; Brazilin: Anti-inflammatory agent; Importazole: Inhibitor; PD 407824: Indoles and derivativesAG 957: Protein tyrosine kinase; Ro-28-1675: Glucokinase activator; Brazilin: NF-kappaB inhibitor and a hepatoprotective agent; Importazole: Transport receptor importin-β; PD 407824: Wee1/Chk1 inhibitorCRC drug candidatesBeklen et al[100], 2020
Based on clinically or experimentally validated approaches
MetforminAntidiabetic agentTreatment of type 2 diabetes mellitusReduces pre-cancerous lesions and cancerous cell proliferationJia et al[102], 2015
Results in better overall survivalBishnoi et al[104], 2018
Causes both apoptosis and autophagy of cultured HT29 cellsSena et al[103], 2018
AspirinNonsteroidal anti-inflammatoryRelieves minor aches, pains, and feversRegular, long-term aspirin use reduces CRC riskChan et al[105], 2005
Reduces CRC cell proliferationReddy et al[106], 2006
Daily use for about 5 yr is efficient in prevention, with a latency time of about 10 yrFlossmann et al[107], 2007
Restrains CRC tumor metastasisJin et al[108], 2019
CimetidineGastrointestinal agentTreatment of ulcers and gastroesophageal reflux diseaseShort course of cimetidine treatment has an impact on patient survivalKelly et al[110], 1999
Inhibits the adhesion of CRC cells and represses spread of cancer cellsKobayashi et al[111], 2000
Reduces frequency of metastasis and increases survival rateMatsumoto et al[112], 2002
Prolongs the probability of recurrence Ali et al[113], 2018
DiclofenacNonsteroidal anti-inflammatoryRelieves pain and inflammationContributes to tumor growth inhibition in colon cancerFalkowski et al[116], 2003
Promotes cell deathArisan et al[117], 2018
ChloroquineAntimalarialTreatment of malariaIncreases cell inhibition and decreases reproductionSasaki et al[119], 2010
Use at high doses (40–160 μM) encourages lysosomal membrane permeabilization and cell deathPark et al[120], 2014
SulindacNonsteroidal anti-inflammatoryReduces pain, swelling, and joint stiffness due to arthritisDecreases final tumor counts and prevents CRC especially when given in intermittent dosesChandra et al[122], 2017
Decreases polyp countDavis et al[123], 2020
MesalazineAnti-inflammatoryTreatment of mild to moderate ulcerative colitisDecreases CRC cell number and enhances apoptosisReinacher-Schick et al[125], 2003
Causes CRC cell cycle arrest and cell deathKoelink et al[126], 2010
DisulfiramEnzyme inhibitorAlcohol addictive disorderPromotes cell viability inhibitionStenvang et al[128], 2018
ErlotinibAnti-neoplasticTreatment of non-small cell lung and pancreatic cancerContributes to enhanced progression-free survival and overall survival of metastatic CRC patientsShi et al[130], 2017