Prognostic factors in colorectal cancer

Aim: to evaluate prognostic factors in colorectal cancer.

Material and methods: published data (publications in PubMed, Scopus, eLIBRARY databases) and own results of treatment of 47 patients with T2-4N0-2M0 colon cancer in 2017–2018. The following prognostic factors were studied: metastasis in regional lymph nodes, tumor site, CEA level, KRAS and BRAF mutation status, microsatellite instability, MUSASHI2, p53, VEGF.

Results: a correlation between tumor progression and the status of regional lymph nodes demonstrated significant differences (p = 0.038): in N0, the risk of progression was 3.8%, in N1 — 14.9%, in N2 — 43.6%. Statistical processing of the results did not reveal significant differences between groups of patients without and with cancer generalization by their age, gender, tumor site, type of lymph node dissection, T stage, differentiation of adenocarcinoma, levels of CEA, mutations of KRAS, MSI, p53, MUSASHI2, VEGF. We used these prognostic factors to determine biological features of the tumor, its aggressiveness and treatment approaches.

Conclusions: the status of regional lymph nodes remains the main factor in determining the prognosis of a colon tumor and in the medical therapy appointment. Molecular genetic factors are currently of great importance for determining tactics in personalized medical treatment.

1. Brenner H, Kloor M, Pox СР. Colorectal cancer. The Lancet. 2014;383:1490–1502.

2. Turano M, Delrio P, Rega D, et al. Promising colorectal cancer biomarkers for precision prevention and therapy. Cancers. 2019;11:1932.

3. Ju Q, Zhao Y-J, Dong Y, et al. Identification of a miRNA‑mRNA network associated with lymph node metastasis in colorectal cancer. Oncology Letters. 2019;18:1179–1188.

4. Martins B, Bulhões G, Cavalcanti I, Martins M, et al. Biomarkers in Colorectal Cancer: The Role of Translational Proteomics Research. Frontiers in Oncology. 2019;9:1284.

5. Kit O.I., Gevorkyan Yu.A., Soldatkina N.V., Vodolazhsky D.I. Frequency and spectrum of KRAS gene mutations in advanced colorectal cancer. Clinical and morphological characteristics. Molecular Medicine. 2015;5:26–29. (in Russ.).

6. Xie M, Li J, Cai Zh, et al. Impact of primary colorectal Cancer location on the KRAS status and its prognostic value. BMC Gastroenterology. 2019;19(46):1–9.

7. Kit O.I., Vodolazhskiy D.I., Gevorkyan Yu.A., Soldatkina N.V. KRAS gene mutation and gender differences in colorectal cancer. International Journal of Biomedicine. 2015;5(1):11–15.

8. Bond CE, Whitehall VLJ. How the BRAF V600E mutation defines a distinct subgroup of colorectal cancer: molecular and clinical Implications. Gastroenterol Res Pract. 2018:9250757.

9. Clarke CN, Kopetz ES. BRAF mutant colorectal cancer as a distinct subset of colorectal cancer: clinical characteristics, clinical behavior, and response to targeted therapies, J Gastrointest Oncol. 2015;6:660–667.

10. Wang J, Shen J, Huang C, et al. Clinicopathological significance of BRAFV600E mutation in colorectal cancer: an updated metaanalysis. J Cancer. 2019;10:2332–2341.

11. Wu M, Kimb Y.S., Ryub H-S. et al. MSI status is associated with distinct clinicopathological features in BRAF mutation colorectal cancer: A systematic review and meta-analysis. Pathology — Research and Practice. 2020;216:1–8.

12. Caputo F, Santini Ch, Bardasi C, et al. BRAF-Mutated Colorectal Cancer: Clinical and Molecular Insights. International Journal of Molecular Sciences. 2019;20:53–69.

13. Yin WH, Fan HZ, Sheng JW, et al. Effect of vascular endothelial growth factor C and collagen triple helix repeat containing 1 expres sion on prognosis of rectal carcinoma patients. Chin. J Gastrointest Surg. 2013;16:673–675.

14. Cullis CA. The use of DNA polymorphisms in genetic mapping. Genet Eng. 2002;24:179–189.

15. Vaksman Z, Garner HR Somatic microsatellite variability as a predictive marker for colorectal cancer and liver cancer progression. Oncotarget. 2015;6:5760–5771.

16. Boland CR. A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998;58:5248–5257.

17. Lynch HT, de la Chapelle A Hereditary colorectal cancer. N Engl J Med. 2003;348:919–932.

18. Mohan HM Microsatellite instability is associated with reduced disease specific survival in stage III colon cancer. Eur J Surg Oncol.2016;42:1680–1686.

19. Wang B, Li F, Zhou X, et al. Is microsatellite instability-high really a favorable prognostic factor for advanced colorectal cancer? A metaanalysis. World Journal of Surgical Oncology. 2019;17(169):1–13.

20. Stintzing S, Tejpar S, Gibbs P, et al. Understanding the role of primary tumour localization in colorectal cancer treatment and outcomes. Eur J Cancer. 2017;84:69–80.

21. Iacopetta B. Are there two sides to colorectal cancer? Int J Cancer. 2002;101:403–408.

22. Petrelli F, Tomasello G, Borgonovo K, et al. Prognostic survival associated with left-sided vs right-sided colon cancer: a systematic review and meta-analysis. JAMA Oncol. 2017 Feb 1;3(2):211-219. DOI: 10.1001/jamaoncol.2016.4227