The features of KRAS gene transcriptional activity and significance in colorectal cancer

  • М. А. Shyshkin
  • V. A. Tumanskiy
Keywords: colorectal cancer, K-RAS gene, Ki-67, TP53, CDH1, CTNNB1.


Colorectal adenocarcinoma (CRA) is the result of numerous mutations accumulation. The aim of the work was to study KRAS gene transcriptional activity at I, II, III, and IV stages of CRA development and to analyze the correlations between KRAS and Ki-67, TP53, CDH1, CTNNB1 genes transcriptional activity. Pathohistological and molecular-genetic study of surgical material from 40 patients with CRA, as well as sectional material of 10 fragments of the distal colonic wall was conducted. The following statistical methods were used: descriptive statistics, χ2 test, Kruskal-Wallis test, Spearman’s rank correlation coefficient. It was established that CRA is characterized by increased KRAS transcriptional activity: Me of mRNA expression is 0.42 (0.36; 0.43) at stage I, 1.31 (1.09; 2.91) at stage II, 1.75 (1.31; 2.93) at stage III, and 2.91 (1.85; 3.50) at stage IV. Decreasing of Ki-67 gene transcriptional activity was revealed: Me of mRNA expression is 3.20 (2.31; 3.59) at stage I, 2.92 (1.80; 3.50) at stage II, 1,27 (1.19; 2.08) at stage III, and 0.52 (0.28; 1.04) at stage IV. As about TP53 gene, increasing of transcriptional activity was detected: Me is 2.15 (0.82; 2.30) at stage I, 2.80 (1.32; 4.50) at stage II, 3.80 (2.32; 6.50) at stage III, 7.80 (5.99; 8.92) at stage IV. Also, a direct medium correlation between the KRAS and TP53 transcriptional activity levels was revealed. There is a decreasing of CDH1 transcriptional activity: Me is 0.88 (0.42; 1.14) at stage I, 0.48 (0.23; 1.13) at stage II, 0.15 (0.09; 0.36) at stage III and 0.08 (0.04; 0.41) at stage IV. A reverse medium correlation between KRAS and CDH1 was revealed. The study of CTNNB1 gene mRNA at different stages of CRA indicated the absence of statistically significant difference: Me is 2.88 (2.38; 5.38) at stage I, 3.83 (2.59; 5.99) at stage II, 2.02 (1.38; 6.95) at stage III, and 2.27 (1.23; 2.93) at stage IV. So, KRAS gene transcriptional activity increases from I to IV stages in CRA, affecting apoptosis and adhesive properties of cancer cells.

Author Biographies

М. А. Shyshkin

Shyshkin M. A., MD, PhD, Associate Professor, Department of Pathological Anatomy and Forensic Medicine, Zaporizhzhіa State Medical University E-mail:, Контактный телефон – 050-298-87-75

V. A. Tumanskiy

Tumanskiy V. A., MD, PhD, DSc, Professor of the Department of Pathological Anatomy and Forensic Medicine, Zaporizhzhia State Medical University, Director of Human Clinical Pathology Institute, Honorary Scientist and Engineering Worker of Ukraine. Контактный телефон – 050-298-87-75


1. Boutin, A. T., Liao, W. T., Wang, M., Hwang, S. S., Karpinets, T. V., Cheung, H., … , DePinho, R. A. (2017). Oncogenic Kras drives invasion and maintains metastases in colorectal cancer. Genes & Development, 31 (4), 370–382. doi: 10.1101/gad.293449.116.

2. Church, J. (2016). Molecular genetics of colorectal cancer. Seminars in Colon and Rectal Surgery, 27 (4), 172–175. doi: 10.1053/j.scrs.2016.04.013.

3. Coulson, R. (2015). Molecular Profiling in Resectable Colorectal Liver Metastases: The Role of KRAS Mutation Status in Assessing Prognosis in the Preoperative Setting. Journal of the advanced practitioner of oncology, 6 (5), 470–474. Retrieved from

4. Du, L., Kim, J. J., Shen, J., Chen, B., & Dai, N. (2017). KRAS and TP53 mutations in inflammatory bowel disease-associated colorectal cancer: a meta-analysis. Oncotarget, 8 (13), 22175–22186. doi: 10.18632/oncotarget.14549.

5. He, X., Chen, Z., Jia, M., & Zhao, O. (2013). Downregulated E-cadherin expression indicates worse prognosis in Asian patients with colorectal cancer: evidence from meta-analysis. PLoS One, 29, 8(7), e70858. doi: 10.1371/journal.pone.0070858.

6. Kwak, M. S., Cha, J. M., Yoon, J. Y., Jeon, J. W., Shin, H. P., Chang, H. J., … Lee, J. (2017). Prognostic value of KRAS codon 13 gene mutation for overall survival in colorectal cancer: Direct and indirect comparison meta-analysis. Medicine (Baltimore), 96 (35), E7882. doi:10.1097/MD.0000000000007882.

7. Lemieux, E., Cagnol, S., Beaudry, K., Carrier, J., & Rivard N. (2015). Oncogenic KRAS signalling promotes the Wnt/β-catenin pathway through LRP6 in colorectal cancer. Oncogene, 34 (38), 4914–4927. doi: 10.1038/onc.2014.416.

8. Loree J. M., & Kopetz, S. (2017). Recent developments in the treatment of metastatic colorectal cancer. Therapeutic Advances in Medical Oncology, 9 (8), 551–564. doi: 10.1177/1758834017714997.

9. Margetis, N., Kouloukoussa, M., Pavlou, K., Vrakas, S., & Mariolis- Sapsakos, T. (2017). K-ras Mutations as the Earliest Driving Force in a Subset of Colorectal Carcinomas. In vivo, 31 (4), 527–542. doi: 10.21873/invivo.11091.

10. Morin, P. J., Kinzler, K. W., & Sparks, A. B. (2016). β-Catenin Mutations: Insights into the APC Pathway and the Power of Genetics. Cancer Research, 76 (19), 5587–5589. doi: 10.1158/0008-5472.CAN-16-2387.

11. Nakamoto, K., Nagahara, H., Maeda, K., Noda, E., Inoue, T., Yashiro, M., Nishiguchi, Y., Ohira, M., & Hirakawa, K. (2013). Expression of E-cadherin and KRAS mutation may serve as biomarkers of cetuximab-based therapy in metastatic colorectal cancer. Oncology letters, 5 (4), 1295–1300. doi: 10.3892/ol.2013.1187.

12. Rezanejad Bardaji, H., Asadi, M. H., & Yaghoobi, M. M. (2018). Long noncoding RNA VIM-AS1 promotes colorectal cancer progression and metastasis by inducing EMT. European Journal of Cell Biology, 7, 1035–1048. doi: 10.1016/j.ejcb.2018.04.004.

13. Temraz, S., Mukherji, D., & Shamseddine, A. (2015). Dual Inhibition of MEK and PI3K Pathway in KRAS and BRAF Mutated Colorectal Cancers. International Journal of Molecular Sciences, 16 (19), 22976–22988. doi: 10.3390/ijms160922976.

14. Thomas, J., Ohtsuka, M., Pichler, M., & Ling, H. (2015). MicroRNAs: Clinical Relevance in Colorectal Cancer. International Journal of Molecular Sciences, 16 (12), 28063–28076. doi: 10.3390/ijms161226080.

15. van Helden, E. J., Menke-van der Houven van Oordt, C. W., Heymans, M. W., Ket, J. C. F., & Verheul, H. M. W. (2017). Optimal use of anti-EGFR monoclonal antibodies for patients with advanced colorectal cancer: a meta-analysis. Cancer metastasis reviews, 36 (2), 395–406. doi: 10.1007/s10555-017-9668-y.

16. Xiao R., Li, C., & Chai, B. (2015). miRNA-144 suppresses proliferation and migration of colorectal cancer cells through GSPT1. Biomedicine & Pharmacotherapy, 74, 138–144. doi: 10.1016/j.biopha.2015.08.006.

17. Xiuli, L., Jakubowski, M., & Hunt, J. L. (2015). KRAS Gene Mutation in Colorectal Cancer Is Correlated With Increased Proliferation and Spontaneous Apoptosis. American Journal of Clinical Pathology, 135 (2), 245–252. doi: 10.1309/AJCP7FO2VAXIVSTP.

18. Yin, Y., Zhang, B., Wang, W., Fei, B., Quan, C., Zhang, J., … Huang, Z. (2014). miR-204-5p inhibits proliferation and invasion and enhances chemotherapeutic sensitivity of colorectal cancer cells by down-regulating RAB22A. Clinical cancer research, 20 (23), 6187–6199. doi: 10.1158/1078-0432.CCR-14-1030.

19. Yoshida, N., Kinugasa, T., Ohshima, K., Yuge, K., Ohchi, T., Fujino, S., … Akagi, Y. (2015). Analysis of Wnt and β-catenin Expression in Advanced Colorectal Cancer. Anticancer Research, 35 (8), 4403–10. Retrieved from
How to Cite
ShyshkinМ. А., & Tumanskiy, V. A. (2019). The features of KRAS gene transcriptional activity and significance in colorectal cancer. Reports of Vinnytsia National Medical University, 23(1), 153-158.