Predictive biomarkers for colorectal cancer: a state-of-the-art systematic review

Abstract Introduction Colorectal cancer (CRC) poses a substantial health burden, with early detection paramount for improved prognosis. This study aims to evaluate potential CRC biomarkers and detection techniques. Materials and Methods This systematic review, reported in adherence to PRISMA Statement 2020 guidelines, collates the latest research on potential biomarkers and detection/prognosis methods for CRC, spanning the last decade. Results Out of the 38 included studies, diverse biomarkers and detection methods emerged, with DNA methylation markers like SFRP2 and SDC2, microRNAs including miR-1290, miR-506, and miR-4316, and serum and plasma markers such as NTS levels and U2 snRNA fragments standing out. Methylated cfDNA and m5C methylation alteration in immune cells of the blood, along with circular RNA, showed promise as diagnostic markers. Meanwhile, techniques involving extracellular vesicles and lateral flow immunoassays exhibited potential for swift and effective CRC screening. Discussion Our state-of-the-art review identifies potential biomarkers, including SFRP2, SDC2, miR-1290, miR-506, miR-4316, and U2 snRNA fragments, with significant potential in enhancing CRC detection. However, comprehensive validation studies and a rigorous evaluation of clinical utility and cost-effectiveness remain necessary before integration into routine clinical practice. Conclusion The findings emphasize the need for continued research into biomarkers and detection methods to improve patient outcomes. Graphical Abstract This state-of-the-art systematic review evaluated potential biomarkers for colorectal cancer (CRC) and synthesized 38 studies. Several biomarkers showed promise for CRC detection, including SFRP2 and SDC2 methylation biomarkers, chiroptical spectroscopy, m6A RNA levels, miR-1290, miR-506, miR-4316, NTS levels, and U2 snRNA fragments. EVs and LFIA were useful for screening.

[1]  Q. Zhi,et al.  Non‐coding RNAs and colitis‐associated cancer: Mechanisms and clinical applications , 2023, Clinical and translational medicine.

[2]  E. Kuipers,et al.  Young-onset colorectal cancer , 2023, Nature Reviews Disease Primers.

[3]  V. Bouvier,et al.  Social inequalities in health: How do they influence the natural history of colorectal cancer? , 2023, Journal of visceral surgery.

[4]  M. Iacucci,et al.  Inflammation-Driven Colorectal Cancer Associated with Colitis: From Pathogenesis to Changing Therapy , 2023, Cancers.

[5]  M. Intrieri,et al.  Liquid Biopsy and Cancer: An Ongoing Story , 2023, Journal of clinical medicine.

[6]  K. Horisberger,et al.  Current Surgical Concepts in Lynch Syndrome and Familial Adenomatous Polyposis , 2023, Visceral Medicine.

[7]  I. Claro,et al.  Early-onset colorectal cancer: A review of current knowledge , 2023, World journal of gastroenterology.

[8]  M. Vinciguerra,et al.  Circulating Histones to Detect and Monitor the Progression of Cancer , 2023, International journal of molecular sciences.

[9]  L. Ming,et al.  5-Methylcytosine (m5C) modification in peripheral blood immune cells is a novel non-invasive biomarker for colorectal cancer diagnosis , 2022, Frontiers in Immunology.

[10]  C. Dive,et al.  Circulating tumour DNA — looking beyond the blood , 2022, Nature Reviews Clinical Oncology.

[11]  M. Caraglia,et al.  Microsatellite Instability: From the Implementation of the Detection to a Prognostic and Predictive Role in Cancers , 2022, International journal of molecular sciences.

[12]  G. Armengol,et al.  Molecular Biomarkers in Cancer , 2022, Biomolecules.

[13]  Nimisha,et al.  Diagnostic and prognostic biomarkers in colorectal cancer and the potential role of exosomes in drug delivery. , 2022, Cellular signalling.

[14]  J. Walter,et al.  DNA methylation biomarkers in colorectal cancer: Clinical applications for precision medicine , 2022, International journal of cancer.

[15]  Mingli Yang,et al.  Molecular Network of Colorectal Cancer and Current Therapeutic Options , 2022, Frontiers in Oncology.

[16]  M. Soloviev,et al.  Colorectal Cancer Diagnosis: The Obstacles We Face in Determining a Non-Invasive Test and Current Advances in Biomarker Detection , 2022, Cancers.

[17]  S. Balasubramanian,et al.  Early detection of cancer , 2022, Science.

[18]  Zhikun Zhao,et al.  Developing a 5-gene prognostic signature for cervical cancer by integrating mRNA and copy number variations , 2022, BMC cancer.

[19]  S. Toden,et al.  Non-coding RNAs as liquid biopsy biomarkers in cancer , 2022, British Journal of Cancer.

[20]  A. Jemal,et al.  Cancer statistics, 2022 , 2022, CA: a cancer journal for clinicians.

[21]  R. Sahu,et al.  Molecular Pathogenesis of Colorectal Cancer with an Emphasis on Recent Advances in Biomarkers, as Well as Nanotechnology-Based Diagnostic and Therapeutic Approaches , 2022, Nanomaterials.

[22]  S. Moghbelinejad,et al.  Evaluation of plasma circ_0006282 as a novel diagnostic biomarker in colorectal cancer , 2021, Journal of clinical laboratory analysis.

[23]  Z. Huang,et al.  Elevated N6-Methyladenosine RNA Levels in Peripheral Blood Immune Cells: A Novel Predictive Biomarker and Therapeutic Target for Colorectal Cancer , 2021, Frontiers in Immunology.

[24]  K. Pantel,et al.  Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as a Liquid Biopsy Marker in Colorectal Cancer , 2021, Cancers.

[25]  B. Oldenburg,et al.  Surveillance and management of colorectal dysplasia and cancer in inflammatory bowel disease: Current practice and future perspectives. , 2021, European journal of internal medicine.

[26]  Pengfei Xu,et al.  Global colorectal cancer burden in 2020 and projections to 2040 , 2021, Translational oncology.

[27]  V. Herlea,et al.  Crosstalk Between DNA Methylation and Gene Mutations in Colorectal Cancer , 2021, Frontiers in Oncology.

[28]  S. Sebens,et al.  Longitudinal Analysis of Circulating Tumor Cells in Colorectal Cancer Patients by a Cytological and Molecular Approach: Feasibility and Clinical Application , 2021, Frontiers in Oncology.

[29]  M. Hegde,et al.  Genetic testing for inherited colorectal cancer and polyposis, 2021 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG) , 2021, Genetics in Medicine.

[30]  A. Buzdin,et al.  FDA-Approved and Emerging Next Generation Predictive Biomarkers for Immune Checkpoint Inhibitors in Cancer Patients , 2021, Frontiers in Oncology.

[31]  J. Sandoval,et al.  Cancer Epigenetic Biomarkers in Liquid Biopsy for High Incidence Malignancies , 2021, Cancers.

[32]  Montserrat Rivas,et al.  Magnetic Lateral Flow Immunoassay for Small Extracellular Vesicles Quantification: Application to Colorectal Cancer Biomarker Detection , 2021, Sensors.

[33]  Zeping Han,et al.  Biomarkers (mRNAs and Non-Coding RNAs) for the Diagnosis and Prognosis of Colorectal Cancer – From the Body Fluid to Tissue Level , 2021, Frontiers in Oncology.

[34]  Jian-Bing Fan,et al.  Sensitive detection of colorectal cancer in peripheral blood by a novel methylation assay , 2021, Clinical epigenetics.

[35]  Anna Danielewicz,et al.  A Review of Colorectal Cancer in Terms of Epidemiology, Risk Factors, Development, Symptoms and Diagnosis , 2021, Cancers.

[36]  J. Larkin,et al.  Predictive biomarkers for response to immune checkpoint inhibition. , 2021, Seminars in cancer biology.

[37]  R. Zheng,et al.  Colorectal cancer burden and trends: Comparison between China and major burden countries in the world , 2021, Chinese journal of cancer research = Chung-kuo yen cheng yen chiu.

[38]  Sakhawat Ali,et al.  An overview of genetic mutations and epigenetic signatures in the course of pancreatic cancer progression , 2021, Cancer and Metastasis Reviews.

[39]  Jeffrey-K Lee,et al.  An update on the epidemiology, molecular characterization, diagnosis, and screening strategies for early-onset colorectal cancer. , 2021, Gastroenterology.

[40]  Mona H. Osman,et al.  Colorectal Cancer in Lebanon: Incidence, Temporal Trends, and Comparison to Regional and Western Countries , 2021, Cancer control : journal of the Moffitt Cancer Center.

[41]  A. Gautreau,et al.  Mutational drivers of cancer cell migration and invasion , 2020, British journal of cancer.

[42]  Z. Fasoulakis,et al.  Role of Oncogenes and Tumor-suppressor Genes in Carcinogenesis: A Review , 2020, AntiCancer Research.

[43]  E. Mayo-Wilson,et al.  PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews , 2020, BMJ.

[44]  P. Kubatka,et al.  Liquid Biopsy is Instrumental for 3PM Dimensional Solutions in Cancer Management , 2020, Journal of clinical medicine.

[45]  F. Couñago,et al.  Watch and wait approach in rectal cancer: Current controversies and future directions , 2020, World journal of gastroenterology.

[46]  D. Ransohoff Evaluating a new cancer screening blood test: Unintended consequences and the need for clarity in policy-making. , 2020, Journal of the National Cancer Institute.

[47]  E. Razmara,et al.  A panel of six-circulating miRNA signature in serum and its potential diagnostic value in colorectal cancer. , 2020, Life sciences.

[48]  O. Ogunwobi,et al.  Biomarkers in Colorectal Cancer: Current Research and Future Prospects , 2020, International journal of molecular sciences.

[49]  Sheri J. Hartman,et al.  American Cancer Society Guideline for Diet and Physical Activity for cancer prevention. , 2020, CA: a cancer journal for clinicians.

[50]  J. Kisiel,et al.  Stool-Based Tests for Colorectal Cancer Screening: Performance Benchmarks Lead to High Expected Efficacy , 2020, Current Gastroenterology Reports.

[51]  Sharifeh Khosravi,et al.  TFPI2 and NDRG4 gene promoter methylation analysis in peripheral blood mononuclear cells are novel epigenetic noninvasive biomarkers for colorectal cancer diagnosis. , 2020, The journal of gene medicine.

[52]  J. A. Lorente Acosta,et al.  Extracellular vesicle-miRNAs as liquid biopsy biomarkers for disease identification and prognosis in metastatic colorectal cancer patients , 2020, Scientific Reports.

[53]  M. Jakovljevic,et al.  A Correlation Study of the Colorectal Cancer Statistics and Economic Indicators in Selected Balkan Countries , 2020, Frontiers in Public Health.

[54]  R. Kotb,et al.  Consensus Guidelines on the Diagnosis of Multiple Myeloma and Related Disorders: Recommendations of the Myeloma Canada Research Network Consensus Guideline Consortium. , 2020, Clinical lymphoma, myeloma & leukemia.

[55]  M. Jenkins,et al.  Utility of the methylated SEPT9 test for the early detection of colorectal cancer: a systematic review and meta-analysis of diagnostic test accuracy , 2020, BMJ open gastroenterology.

[56]  Monjur Ahmed Colon Cancer: A Clinician’s Perspective in 2019 , 2020, Gastroenterology research.

[57]  S. Haan,et al.  Prognostic and Predictive Molecular Biomarkers for Colorectal Cancer: Updates and Challenges , 2020, Cancers.

[58]  Xiangwei Zhao,et al.  A novel plasma based early colorectal cancer screening assay base on methylated SDC2 and SFRP2. , 2020, Clinica chimica acta; international journal of clinical chemistry.

[59]  A. Goel,et al.  Epigenetics of colorectal cancer: biomarker and therapeutic potential , 2020, Nature Reviews Gastroenterology & Hepatology.

[60]  Chyke A Doubeni,et al.  Causes of Socioeconomic Disparities in Colorectal Cancer and Intervention Framework and Strategies. , 2020, Gastroenterology.

[61]  J. Casal,et al.  Identification and Validation of Stage‐Associated Serum Biomarkers in Colorectal Cancer Using MS‐Based Procedures , 2020, Proteomics. Clinical applications.

[62]  F. Ris,et al.  Circulating Tumour Cells, Circulating Tumour DNA and Circulating Tumour miRNA in Blood Assays in the Different Steps of Colorectal Cancer Management, a Review of the Evidence in 2019 , 2019, BioMed research international.

[63]  J. Nielsen,et al.  The Translational Status of Cancer Liquid Biopsies , 2019, Regenerative Engineering and Translational Medicine.

[64]  M. Del Cornò,et al.  Revisiting the impact of lifestyle on colorectal cancer risk in a gender perspective. , 2019, Critical reviews in oncology/hematology.

[65]  O. Ogunbiyi,et al.  Clinicopathological correlations of mesenteric fibrosis and evaluation of a novel biomarker for fibrosis detection in small bowel neuroendocrine neoplasms , 2019, Endocrine.

[66]  Rajesh Sharma An examination of colorectal cancer burden by socioeconomic status: evidence from GLOBOCAN 2018 , 2019, EPMA Journal.

[67]  R. Mohamed,et al.  Assessment of Serum MicroRNA-21 Gene Expression for Diagnosis and Prognosis of Colorectal Cancer , 2019, Journal of Gastrointestinal Cancer.

[68]  S. Kopetz,et al.  Current and Future Horizons of Patient-Derived Xenograft Models in Colorectal Cancer Translational Research , 2019, Cancers.

[69]  E. Giovannucci,et al.  Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies , 2019, Nature Reviews Gastroenterology & Hepatology.

[70]  R. Lothe,et al.  Biomarker-guided therapy for colorectal cancer: strength in complexity , 2019, Nature Reviews Clinical Oncology.

[71]  Marnix Jansen,et al.  British Society of Gastroenterology guidelines on the diagnosis and management of patients at risk of gastric adenocarcinoma , 2019, Gut.

[72]  Qin Li,et al.  Mismatch repair deficiency/microsatellite instability-high as a predictor for anti-PD-1/PD-L1 immunotherapy efficacy , 2019, Journal of Hematology & Oncology.

[73]  A. Darzi,et al.  Exploratory Analysis of Plasma Neurotensin as a Novel Biomarker for Early Detection of Colorectal Polyp and Cancer , 2019, Hormones and Cancer.

[74]  N. Cho,et al.  p53 expression status is associated with cancer-specific survival in stage III and high-risk stage II colorectal cancer patients treated with oxaliplatin-based adjuvant chemotherapy , 2019, British Journal of Cancer.

[75]  Sarah K. McGill,et al.  Look, but don't touch: what not to do in managing large colorectal polyps. , 2019, Gastrointestinal endoscopy.

[76]  N. Pavlidis,et al.  The Developing Story of Predictive Biomarkers in Colorectal Cancer , 2019, Journal of personalized medicine.

[77]  Prashanth Rawla,et al.  Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors , 2019, Przeglad gastroenterologiczny.

[78]  Tamaki Yamada,et al.  Urinary Cysteine-Rich Protein 61 and Trefoil Factor 3 as Diagnostic Biomarkers for Colorectal Cancer1 , 2019, Translational oncology.

[79]  Juan Cai,et al.  Long Noncoding RNAs Serve as Potential Diagnostic Biomarkers for Colorectal Cancer , 2019, Journal of Cancer.

[80]  A. Pretorius,et al.  Biomarkers for Stratification in Colorectal Cancer: MicroRNAs , 2019, Cancer control : journal of the Moffitt Cancer Center.

[81]  S. Faria,et al.  Tumor markers: myths and facts unfolded , 2018, Abdominal Radiology.

[82]  Ted Gansler,et al.  A blueprint for cancer screening and early detection: Advancing screening’s contribution to cancer control , 2018, CA: a cancer journal for clinicians.

[83]  D. Sabry,et al.  Role of miRNA-210, miRNA-21 and miRNA-126 as diagnostic biomarkers in colorectal carcinoma: impact of HIF-1α-VEGF signaling pathway , 2018, Molecular and Cellular Biochemistry.

[84]  Hong-Quan Duong,et al.  The molecular characteristics of colorectal cancer: Implications for diagnosis and therapy. , 2018, Oncology letters.

[85]  H. Ren,et al.  Blood-based DNA Methylation Biomarkers for Early Detection of Colorectal Cancer , 2018, Journal of proteomics & bioinformatics.

[86]  L. Croner,et al.  Analytical validation of a novel multiplex test for detection of advanced adenoma and colorectal cancer in symptomatic patients , 2018, Journal of pharmaceutical and biomedical analysis.

[87]  M. Esteller,et al.  A new approach to epigenome-wide discovery of non-invasive methylation biomarkers for colorectal cancer screening in circulating cell-free DNA using pooled samples , 2018, Clinical Epigenetics.

[88]  H. Grabsch,et al.  Prognostic DNA methylation markers for sporadic colorectal cancer: a systematic review , 2018, Clinical Epigenetics.

[89]  I. Endo,et al.  Detection of gas components as a novel diagnostic method for colorectal cancer , 2018, Annals of gastroenterological surgery.

[90]  O. Shaker,et al.  Association of rs6983267 at 8q24, HULC rs7763881 polymorphisms and serum lncRNAs CCAT2 and HULC with colorectal cancer in Egyptian patients , 2017, Scientific Reports.

[91]  A. Zauber,et al.  A Comparison of Fecal Immunochemical and High-Sensitivity Guaiac Tests for Colorectal Cancer Screening , 2017, The American Journal of Gastroenterology.

[92]  H. Salehiniya,et al.  Colorectal cancer in the world: incidence,mortality and risk factors , 2017 .

[93]  D. Moralejo,et al.  Critical Appraisal Toolkit (CAT) for assessing multiple types of evidence. , 2017, Canada communicable disease report = Releve des maladies transmissibles au Canada.

[94]  F. Lammert,et al.  Cancer-associated circulating large extracellular vesicles in cholangiocarcinoma and hepatocellular carcinoma. , 2017, Journal of hepatology.

[95]  C. Sohn,et al.  Serum CEA and CA 19-9 Levels are Associated with the Presence and Severity of Colorectal Neoplasia , 2017, Yonsei medical journal.

[96]  H. Brenner,et al.  Diagnostic performance of flexible sigmoidoscopy combined with fecal immunochemical test in colorectal cancer screening: meta-analysis and modeling , 2017, European Journal of Epidemiology.

[97]  P. Krawczyk,et al.  Evaluation of miR-506 and miR-4316 expression in early and non-invasive diagnosis of colorectal cancer , 2017, International Journal of Colorectal Disease.

[98]  C. Are,et al.  Colorectal cancer—global burden, trends, and geographical variations , 2017, Journal of surgical oncology.

[99]  Mintu Pal,et al.  Predictive and prognostic biomarkers in colorectal cancer: A systematic review of recent advances and challenges. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[100]  Yoko Yamamoto,et al.  LINE-1 hypomethylation status of circulating cell-free DNA in plasma as a biomarker for colorectal cancer , 2017, Oncotarget.

[101]  E. Conant,et al.  Follow-Up of Abnormal Breast and Colorectal Cancer Screening by Race/Ethnicity. , 2016, American journal of preventive medicine.

[102]  Y. Toiyama,et al.  Circulating microRNA-1290 as a novel diagnostic and prognostic biomarker in human colorectal cancer. , 2016, Annals of oncology : official journal of the European Society for Medical Oncology.

[103]  Y. Toiyama,et al.  Elevated serum concentration of monocyte chemotactic protein 4 (MCP‐4) as a novel non‐invasive prognostic and predictive biomarker for detection of metastasis in colorectal cancer , 2016, Journal of surgical oncology.

[104]  Karen M Kuntz,et al.  Estimation of Benefits, Burden, and Harms of Colorectal Cancer Screening Strategies: Modeling Study for the US Preventive Services Task Force. , 2016, JAMA.

[105]  Ahmedin Jemal,et al.  Global patterns and trends in colorectal cancer incidence and mortality , 2016, Gut.

[106]  U. Gezer,et al.  Histone Methylation Marks on Circulating Nucleosomes as Novel Blood-Based Biomarker in Colorectal Cancer , 2015, International journal of molecular sciences.

[107]  A. Jemal,et al.  Public Health Impact of Achieving 80% Colorectal Cancer Screening Rates in the United States by 2018 , 2015, Cancer.

[108]  C. Dang,et al.  Plasma miR-183 predicts recurrence and prognosis in patients with colorectal cancer , 2015, Cancer biology & therapy.

[109]  Catherine Bailey,et al.  Detection of Colorectal Cancer (CRC) by Urinary Volatile Organic Compound Analysis , 2014, PloS one.

[110]  E. Chan,et al.  Global fecal microRNA profiling in the identification of biomarkers for colorectal cancer screening among Asians. , 2014, Oncology reports.

[111]  Jian Qi,et al.  Detection of promoter hypermethylation of Wnt antagonist genes in fecal samples for diagnosis of early colorectal cancer. , 2014, World journal of gastroenterology.

[112]  C. Rüegg,et al.  A novel gene expression signature in peripheral blood mononuclear cells for early detection of colorectal cancer , 2014, Alimentary Pharmacology and Therapeutics.

[113]  K. Braunschweiger,et al.  Multiplexed VeraCode bead-based serological immunoassay for colorectal cancer. , 2013, Journal of immunological methods.

[114]  A. Watson,et al.  Proteomic profiling of a mouse model of acute intestinal Apc deletion leads to identification of potential novel biomarkers of human colorectal cancer (CRC). , 2013, Biochemical and biophysical research communications.

[115]  J. Hurley,et al.  The molecular genetics of colorectal cancer , 2013, Frontline Gastroenterology.

[116]  Irene Moya,et al.  microRNA expression profile in stage III colorectal cancer: circulating miR-18a and miR-29a as promising biomarkers. , 2013, Oncology reports.

[117]  Michael J. Walker,et al.  A caspase-3 ‘death-switch' in colorectal cancer cells for induced and synchronous tumor apoptosis in vitro and in vivo facilitates the development of minimally invasive cell death biomarkers , 2013, Cell Death and Disease.

[118]  C. Andersen,et al.  Circulating U2 small nuclear RNA fragments as a novel diagnostic biomarker for pancreatic and colorectal adenocarcinoma , 2013, International journal of cancer.

[119]  D. Dolinoy,et al.  Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. , 2012, The Journal of nutritional biochemistry.

[120]  S. Crotta,et al.  High rate of advanced adenoma detection in 4 rounds of colorectal cancer screening with the fecal immunochemical test. , 2012, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[121]  L. Migliore,et al.  Epigenetics of colorectal cancer , 2012, Clinical genetics.

[122]  R. Ricciardi,et al.  Screening options and recommendations for colorectal cancer. , 2009, Clinics in colon and rectal surgery.

[123]  Christian Pilarsky,et al.  Circulating methylated SEPT9 DNA in plasma is a biomarker for colorectal cancer. , 2009, Clinical chemistry.

[124]  C S Berkey,et al.  Cancer incidence and mortality: the priority of screening frequency and population coverage. , 1997, The Milbank quarterly.