Distant Metastasis in Colorectal Cancer Patients-Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review

doi:10.3390/ijms21155255

. 2020 Jul 24;21(15):5255.

doi: 10.3390/ijms21155255.

Distant Metastasis in Colorectal Cancer Patients-Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review

Stanislav Filip¹, Veronika Vymetalkova^{2

3

4}, Jiri Petera¹, Ludmila Vodickova^{2

3

4}, Ondrej Kubecek¹, Stanislav John¹, Filip Cecka⁵, Marketa Krupova⁶, Monika Manethova⁶, Klara Cervena^{2

4}, Pavel Vodicka^{2

3

4}

Affiliations

¹ Department of Oncology and Radiotherapy, Charles University, Faculty of Medicine in Hradec Kralove, Šimkova 870, 50001 Hradec Králové, Czech Republic.
² Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic.
³ Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655, 32300 Pilsen, Czech Republic.
⁴ Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov 4, 12800 Prague, Czech Republic.
⁵ Department of Surgery, University Hospital in Hradec Kralove, Sokolská 581, 50005 Hradec Králové, Czech Republic.
⁶ The Fingerland Department of Pathology, University Hospital in Hradec Kralove, Sokolská 581, 50005 Hradec Králové, Czech Republic.

PMID: 32722130
PMCID: PMC7432613
DOI: 10.3390/ijms21155255

Distant Metastasis in Colorectal Cancer Patients-Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review

Stanislav Filip et al. Int J Mol Sci. 2020.

. 2020 Jul 24;21(15):5255.

doi: 10.3390/ijms21155255.

Authors

Affiliations

¹ Department of Oncology and Radiotherapy, Charles University, Faculty of Medicine in Hradec Kralove, Šimkova 870, 50001 Hradec Králové, Czech Republic.
² Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic.
³ Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655, 32300 Pilsen, Czech Republic.
⁴ Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov 4, 12800 Prague, Czech Republic.
⁵ Department of Surgery, University Hospital in Hradec Kralove, Sokolská 581, 50005 Hradec Králové, Czech Republic.
⁶ The Fingerland Department of Pathology, University Hospital in Hradec Kralove, Sokolská 581, 50005 Hradec Králové, Czech Republic.

PMID: 32722130
PMCID: PMC7432613
DOI: 10.3390/ijms21155255

Abstract

Colorectal cancer (CRC) remains a serious health problem worldwide. Approximately half of patients will develop distant metastasis after CRC resection, usually with very poor prognosis afterwards. Because patient performance after distant metastasis surgery remains very heterogeneous, ranging from death within 2 years to a long-term cure, there is a clinical need for a precise risk stratification of patients to aid pre- and post-operative decisions. Furthermore, around 20% of identified CRC cases are at IV stage disease, known as a metastatic CRC (mCRC). In this review, we overview possible molecular and clinicopathological biomarkers that may provide prognostic and predictive information for patients with distant metastasis. These may comprise sidedness of the tumor, molecular profile and epigenetic characteristics of the primary tumor and arising metastatic CRC, and early markers reflecting cancer cell resistance in mCRC and biomarkers identified from transcriptome. This review discusses current stage in employment of these biomarkers in clinical practice as well as summarizes current experience in identifying predictive biomarkers in mCRC treatment.

Keywords: biomarkers; colon cancer; liver metastasis; metastatic colorectal cancer; predictive markers.

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Conflict of interest statement

The authors declare no conflict of interests.

Figures

**Figure 1**
The epithelial–mesenchymal transformation (EMT) and cancer stem cells (CSC) at the crossroads towards drug resistance [68,69]. CSC subpopulations show EMT phenotypes. See text for details. MET: Mesenchymal-epithelial transformation.

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References

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[1] Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2019. CA Cancer J. Clin. 2019;69:7–34. doi: 10.3322/caac.21551. - DOI - PubMed

[2] Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2019. CA Cancer J. Clin. 2019;69:7–34. doi: 10.3322/caac.21551. - DOI - PubMed

[3] Siegel R.L., Miller K.D., Goding Sauer A., Fedewa S.A., Butterly L.F., Anderson J.C., Cercek A., Smith R.A., Jemal A. Colorectal cancer statistics, 2020. CA A Cancer J. Clin. 2020;70:145–164. doi: 10.3322/caac.21601. - DOI - PubMed

[4] Siegel R.L., Miller K.D., Goding Sauer A., Fedewa S.A., Butterly L.F., Anderson J.C., Cercek A., Smith R.A., Jemal A. Colorectal cancer statistics, 2020. CA A Cancer J. Clin. 2020;70:145–164. doi: 10.3322/caac.21601. - DOI - PubMed

[5] Oki E., Ando K., Nakanishi R., Sugiyama M., Nakashima Y., Kubo N., Kudou K., Saeki H., Nozoe T., Emi Y., et al. Recent advances in treatment for colorectal liver metastasis. Ann. Gastroenterol. Surg. 2018;2:167–175. doi: 10.1002/ags3.12071. - DOI - PMC - PubMed

[6] Oki E., Ando K., Nakanishi R., Sugiyama M., Nakashima Y., Kubo N., Kudou K., Saeki H., Nozoe T., Emi Y., et al. Recent advances in treatment for colorectal liver metastasis. Ann. Gastroenterol. Surg. 2018;2:167–175. doi: 10.1002/ags3.12071. - DOI - PMC - PubMed

[7] Kim H.J., Choi G. Clinical Implications of Lymph Node Metastasis in Colorectal Cancer: Current Status and Future Perspectives. Ann. Coloproctol. 2019;35:109–117. doi: 10.3393/ac.2019.06.12. - DOI - PMC - PubMed

[8] Kim H.J., Choi G. Clinical Implications of Lymph Node Metastasis in Colorectal Cancer: Current Status and Future Perspectives. Ann. Coloproctol. 2019;35:109–117. doi: 10.3393/ac.2019.06.12. - DOI - PMC - PubMed

[9] Fessler E., Dijkgraaf F.E., De Sousa E., Melo F., Medema J.P. Cancer stem cell dynamics in tumor progression and metastasis: Is the microenvironment to blame? Cancer Lett. 2013;341:97–104. doi: 10.1016/j.canlet.2012.10.015. - DOI - PubMed

[10] Fessler E., Dijkgraaf F.E., De Sousa E., Melo F., Medema J.P. Cancer stem cell dynamics in tumor progression and metastasis: Is the microenvironment to blame? Cancer Lett. 2013;341:97–104. doi: 10.1016/j.canlet.2012.10.015. - DOI - PubMed

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Distant Metastasis in Colorectal Cancer Patients-Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review

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Distant Metastasis in Colorectal Cancer Patients-Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review

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