Comparison of KRAS Mutation Status with Clinical Parameters in Colon Adenocarcinoma

Barış Boylu; Mustafa Türkmen

doi:10.31466/kfbd.981849

EN TR

Comparison of KRAS Mutation Status with Clinical Parameters in Colon Adenocarcinoma

Abstract

KRAS mutations are mutually exclusive with other activating mutations on EGFR pathway. Detection of KRAS mutations associated with tumorigenesis, predicates the lack of other mutations on the same pathway and shows that the application of targeted therapy approaches which target other proteins in EGFR-MAPK pathway ineffective. In this study, frequency of KRAS mutations in colorectal cancer and relationship between KRAS mutation status and other clinical features were assessed. KRAS mutations were detected in 47,7% of the cases included in our study. We determined that 76% of the mutations were located in codon 12, 9% of the mutations were located in codon 13, 9% of the mutations were located in codon 61 and 6% of the mutations located in codon 117 or codon 146. Determination of mutation rates and association of mutations with clinical features for different populations are important for planning of the treatment strategies nationwide. In our study, we have demonstrated that KRAS mutation status and clinical features associated with KRAS mutation is in accordance with the literature. We have determined that there is statistically significant correlation between grade and KRAS mutation status.

Keywords

Colorectal cancer, KRAS oncogene, Anti-EGFR treatment

Kolon Adenokarsinomlarında KRAS Mutasyon Durumunun Klinik Veriler ile Karşılaştırılması

Abstract

KRAS mutasyonu EGFR yolağındaki diğer aktifleştirici mutasyonlarla birbirini dışlayan özellik göstermektedir. Tümörijenez ile bağlantılı KRAS mutasyonlarının tespiti, aynı yolak üzerinde başka mutasyonların yokluğunu da büyük ölçüde göstermekte ve dolayısıyla EGFR-MAPK yolağı üzerindeki başka proteinleri hedefleyen akıllı ilaçların kullanımının fayda sağlamayacağını göstermektedir. Bu çalışmada kolorektal kanser vakalarında KRAS mutasyonu görülme sıklığı ve mutasyon durumunun diğer klinik veriler ile ilişkisi incelenmiştir. KRAS mutasyonu çalışmamıza dahil edilen vakaların %47,7’sinde tespit edilmiştir. KRAS mutasyonlarının %76’sının 12. kodonda, %9’unun 13. kodonda, %9’unun 61. kodonda ve %6’sının 117. veya 146. kodonda gerçekleştiği tespit edilmiştir. Farklı populasyonlarda değişebilen mutasyon oranlarının ve mutasyonların klinik özelliklerle ilişkisinin tespit edilmesi ulusal tedavi stratejilerinin planlanması açısından büyük öneme sahiptir. Çalışmamızda KRAS mutasyon durumunun ve KRAS mutasyonu ile bağlantılı klinik özelliklerin literatür ile uyumlu olduğu gösterilmiştir. Çalışmamızda KRAS mutasyon durumu ile tümör grade’i arasında istatistiki olarak anlamlı korelasyonun varlığı tespit edilmiştir.

Keywords

Kolorektal kanser, KRAS onkogeni, Anti-EGFR tedavisi

References

Abudabous, A., Drah, M., Aldehmani, M., Parker, I., & Alqawi, O. (2021). KRAS mutations in patients with colorectal cancer in Libya. Molecular and clinical oncology, 15(4), 197. https://doi.org/10.3892/mco.2021.2359.
Awidi, M., Ababneh, N., Shomaf, M., Al Fararjeh, F., Owaidi, L., AlKhatib, M., Al Tarawneh, B., & Awidi, A. (2019). KRAS and NRAS mutational gene profile of metastatic colorectal cancer patients in Jordan. PloS one, 14(12), e0226473. https://doi.org/10.1371/journal.pone.0226473
Babat, I., Polat, H., Umar Gursu, R., Bashan, Y., Kırık, A., Bektas, H., Sarı, S., & Usul Afşar, Ç. (2021). The effect of mutation status, pathological features and tumor location on prognosis ın patients with colorectal cancer. Revista da Associacao Medica Brasileira (1992), 67(2), 185–189. https://doi.org/10.1590/1806-9282.67.02.20200321.
Baskin, Y., Dagdeviren, Y. K., Calibasi, G., Canda, A. E., Sarioglu, S., Ellidokuz, H., & Oztop, I. (2014). KRAS mutation profile differences between rectosigmoid localized adenocarcinomas and colon adenocarcinomas. Journal of gastrointestinal oncology, 5(4), 265.
Belardinilli, F., Capalbo, C., Malapelle, U., Pisapia, P., Raimondo, D., Milanetti, E., Yasaman, M., Liccardi, C., Paci, P., Sibilio, P., Pepe, F., Bonfiglio, C., Mezi, S., Magri, V., Coppa, A., Nicolussi, A., Gradilone, A., Petroni, M., Di Giulio, S., Fabretti, F., … Giannini, G. (2020). Clinical Multigene Panel Sequencing Identifies Distinct Mutational Association Patterns in Metastatic Colorectal Cancer. Frontiers in oncology, 10, 560. https://doi.org/10.3389/fonc.2020.00560.
Belli, S., Esposito, D., Servetto, A., Pesapane, A., Formisano, L., & Bianco, R. (2020). c-Src and EGFR Inhibition in Molecular Cancer Therapy: What Else Can We Improve?. Cancers, 12(6), 1489. https://doi.org/10.3390/cancers12061489.
Cai, W. Q., Zeng, L. S., Wang, L. F., Wang, Y. Y., Cheng, J. T., Zhang, Y., Han, Z. W., Zhou, Y., Huang, S. L., Wang, X. W., Peng, X. C., Xiang, Y., Ma, Z., Cui, S. Z., & Xin, H. W. (2020). The Latest Battles Between EGFR Monoclonal Antibodies and Resistant Tumor Cells. Frontiers in oncology, 10, 1249. https://doi.org/10.3389/fonc.2020.01249
Chang, X. N., Shang, F. M., Jiang, H. Y., Chen, C., Zhao, Z. Y., Deng, S. H., Fan, J., Dong, X. C., Yang, M., Li, Y., Cai, K. L., Liu, L., Liu, H. L., & Nie, X. (2021). Clinicopathological Features and Prognostic Value of KRAS/NRAS/BRAF Mutations in Colorectal Cancer Patients of Central China. Current medical science, 41(1), 118–126. https://doi.org/10.1007/s11596-021-2326-1.
Davis, D. M., Marcet, J. E., Frattini, J. C., Prather, A. D., Mateka, J. J., & Nfonsam, V. N. (2011). Is it time to lower the recommended screening age for colorectal cancer?. Journal of the American College of Surgeons, 213(3), 352-361.
Eraslan, E., Doğan, M., Yildiz, F., İlhan, A., & Öksüzoğlu, Ö. B. (2021). Treatment options after regorafenib failure in metastatic colorectal cancer. European review for medical and pharmacological sciences, 25(9), 3470–3477. https://doi.org/10.26355/eurrev_202105_25828.

Fu, J., Yang, J., Tan, Y., Jiang, M., Wen, F., Huang, Y., ... & Yuan, Y. (2014). Young patients (≤ 35years old) with colorectal cancer have worse outcomes due to more advanced disease: a 30-year retrospective review. Medicine, 93(23).
García-Foncillas, J., Sunakawa, Y., Aderka, D., Wainberg, Z., Ronga, P., Witzler, P., & Stintzing, S. (2019). Distinguishing features of cetuximab and panitumumab in colorectal cancer and other solid tumors. Frontiers in oncology, 9, 849.
Hsu, H. C., Thiam, T. K., Lu, Y. J., Yeh, C. Y., Tsai, W. S., You, J. F., ... & Yang, T. S. (2016). Mutations of KRAS/NRAS/BRAF predict cetuximab resistance in metastatic colorectal cancer patients. Oncotarget, 7(16), 22257.
Hobbs, G. A., Wittinghofer, A., & Der, C. J. (2016). Selective targeting of the KRAS G12C mutant: kicking KRAS when it’s down. Cancer Cell, 29(3), 251-253.
Holch, J. W., Demmer, M., Lamersdorf, C., Michl, M., Schulz, C., von Einem, J. C., Modest, D. P., & Heinemann, V. (2017). Pattern and Dynamics of Distant Metastases in Metastatic Colorectal Cancer. Visceral medicine, 33(1), 70–75. https://doi.org/10.1159/000454687.
Imamura, Y., Lochhead, P., Yamauchi, M., Kuchiba, A., Qian, Z. R., Liao, X., ... & Ogino, S. (2014). Analyses of clinicopathological, molecular, and prognostic associations of KRAS codon 61 and codon 146 mutations in colorectal cancer: cohort study and literature review. Molecular cancer, 13(1), 1-15.
Ikoma, T., Shimokawa, M., Kotaka, M., Matsumoto, T., Nagai, H., Boku, S., Shibata, N., Yasui, H., & Satake, H. (2021). Clinical and prognostic features of patients with detailed RAS/BRAF-mutant colorectal cancer in Japan. BMC cancer, 21(1), 518. https://doi.org/10.1186/s12885-021-08271-z.
Kit, O. I., Vodolazhskiy, D. I., Gevorkyan, Y. A., & Soldatkina, N. V. (2015). KRAS gene mutations and gender differences in colorectal cancer. Int. J. Biomed, 5(1), 11-15.
Kwak, M. S., Cha, J. M., Cho, Y. H., Kim, S. H., Yoon, J. Y., Jeon, J. W., Shin, H. P., Joo, K. R., & Lee, J. I. (2018). Clinical Predictors for KRAS Codon 13 Mutations in Patients With Colorectal Cancer. Journal of clinical gastroenterology, 52(5), 431–436. https://doi.org/10.1097/MCG.0000000000000809
László, L., Kurilla, A., Takács, T., Kudlik, G., Koprivanacz, K., Buday, L., & Vas, V. (2021). Recent Updates on the Significance of KRAS Mutations in Colorectal Cancer Biology. Cells, 10(3), 667. https://doi.org/10.3390/cells10030667
Li, Q. H., Wang, Y. Z., Tu, J., Liu, C. W., Yuan, Y. J., Lin, R., He, W. L., Cai, S. R., He, Y. L., & Ye, J. N. (2020). Anti-EGFR therapy in metastatic colorectal cancer: mechanisms and potential regimens of drug resistance. Gastroenterology report, 8(3), 179–191. https://doi.org/10.1093/gastro/goaa026
Lee, J., Lee, K. S., Kim, H., Jeong, H., Choi, M. J., Yoo, H. W., Han, T. H., & Lee, H. (2020). The relationship between metabolic syndrome and the incidence of colorectal cancer. Environmental health and preventive medicine, 25(1), 6. https://doi.org/10.1186/s12199-020-00845-w.
Lee, S. K., Cho, Y. H., Cha, P. H., Yoon, J. S., Ro, E. J., Jeong, W. J., Park, J., Kim, H., Il Kim, T., Min, D. S., Han, G., & Choi, K. Y. (2018). A small molecule approach to degrade RAS with EGFR repression is a potential therapy for KRAS mutation-driven colorectal cancer resistance to cetuximab. Experimental & molecular medicine, 50(11), 1–12. https://doi.org/10.1038/s12276-018-0182-2
London, M., & Gallo, E. (2020). Epidermal growth factor receptor (EGFR) involvement in epithelial-derived cancers and its current antibody-based immunotherapies. Cell biology international, 44(6), 1267–1282. https://doi.org/10.1002/cbin.11340
Manfredi, S., Lepage, C., Hatem, C., Coatmeur, O., Faivre, J., & Bouvier, A. M. (2006). Epidemiology and management of liver metastases from colorectal cancer. Annals of surgery, 244(2), 254.
Menyhárd, D. K., Pálfy, G., Orgován, Z., Vida, I., Keserű, G. M., & Perczel, A. (2020). Structural impact of GTP binding on downstream KRAS signaling. Chemical science, 11(34), 9272–9289. https://doi.org/10.1039/d0sc03441j
Peeters, M., Douillard, J. Y., Van Cutsem, E., Siena, S., Zhang, K., Williams, R., & Wiezorek, J. (2013). Mutant KRAS codon 12 and 13 alleles in patients with metastatic colorectal cancer: assessment as prognostic and predictive biomarkers of response to panitumumab. J Clin Oncol, 31(6), 759-765.
Prior, I. A., Hood, F. E., & Hartley, J. L. (2020). The frequency of Ras mutations in cancer. Cancer research, 80(14), 2969-2974.
Rawla, P., Sunkara, T., & Barsouk, A. (2019). Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Przeglad gastroenterologiczny, 14(2), 89–103. https://doi.org/10.5114/pg.2018.81072
Russo, A., Franchina, T., Ricciardi, G. R. R., Picone, A., Ferraro, G., Zanghì, M., ... & Adamo, V. (2015). A decade of EGFR inhibition in EGFR-mutated non small cell lung cancer (NSCLC): Old successes and future perspectives. Oncotarget, 6(29), 26814.
Sanchez-Ibarra, H. E., Jiang, X., Gallegos-Gonzalez, E. Y., Cavazos-González, A. C., Chen, Y., Morcos, F., & Barrera-Saldaña, H. A. (2020). KRAS, NRAS, and BRAF mutation prevalence, clinicopathological association, and their application in a predictive model in Mexican patients with metastatic colorectal cancer: A retrospective cohort study. PloS one, 15(7), e0235490. https://doi.org/10.1371/journal.pone.0235490.
Timar, J., & Kashofer, K. (2020). Molecular epidemiology and diagnostics of KRAS mutations in human cancer. Cancer metastasis reviews, 39(4), 1029–1038. https://doi.org/10.1007/s10555-020-09915-5
Ucar, G., Ergun, Y., Aktürk Esen, S., Acikgoz, Y., Dirikoc, M., Esen, İ., Bal, Ö., & Uncu, D. (2020). Prognostic and predictive value of KRAS mutation number in metastatic colorectal cancer. Medicine, 99(39), e22407. https://doi.org/10.1097/MD.0000000000022407.
Varlı G., Özercan İH. & Önalan E. (2020). Kolon adenokarsinomlarında KRAS mutasyonlarının sıklığı ve lenf nodu metastazı ile ilişkisi. Hitit Med J 2020;2(2): 36-41.
Vaughn, C. P., ZoBell, S. D., Furtado, L. V., Baker, C. L., & Samowitz, W. S. (2011). Frequency of KRAS, BRAF, and NRAS mutations in colorectal cancer. Genes, Chromosomes and Cancer, 50(5), 307-312.
Vitiello, P. P., Cardone, C., Martini, G., Ciardiello, D., Belli, V., Matrone, N., ... & Martinelli, E. (2019). Receptor tyrosine kinase-dependent PI3K activation is an escape mechanism to vertical suppression of the EGFR/RAS/MAPK pathway in KRAS-mutated human colorectal cancer cell lines. Journal of Experimental & Clinical Cancer Research, 38(1), 1-12.
Wangefjord, S., Sundström, M., Zendehrokh, N., Lindquist, K. E., Nodin, B., Jirström, K., & Eberhard, J. (2013). Sex differences in the prognostic significance of KRAS codons 12 and 13, and BRAF mutations in colorectal cancer: a cohort study. Biology of sex differences, 4(1), 1-9.
Wong, M., Huang, J., Lok, V., Wang, J., Fung, F., Ding, H., & Zheng, Z. J. (2021). Differences in Incidence and Mortality Trends of Colorectal Cancer Worldwide Based on Sex, Age, and Anatomic Location. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 19(5), 955–966.e61. https://doi.org/10.1016/j.cgh.2020.02.026

Details

Primary Language

English

Subjects

-

Journal Section

Research Article

Authors

Barış Boylu ^*
0000-0003-1872-8422
Türkiye

Mustafa Türkmen
0000-0001-6700-5947
Türkiye

Publication Date

December 15, 2021

Submission Date

August 12, 2021

Acceptance Date

November 14, 2021

Published in Issue

Year 2021 Volume: 11 Number: 2

DOI

https://doi.org/10.31466/kfbd.981849

IZ

https://izlik.org/JA58MC54NX

APA

Boylu, B., & Türkmen, M. (2021). Comparison of KRAS Mutation Status with Clinical Parameters in Colon Adenocarcinoma. Karadeniz Fen Bilimleri Dergisi, 11(2), 648-662. https://doi.org/10.31466/kfbd.981849

AMA

1.Boylu B, Türkmen M. Comparison of KRAS Mutation Status with Clinical Parameters in Colon Adenocarcinoma. KFBD. 2021;11(2):648-662. doi:10.31466/kfbd.981849

Chicago

Boylu, Barış, and Mustafa Türkmen. 2021. “Comparison of KRAS Mutation Status With Clinical Parameters in Colon Adenocarcinoma”. Karadeniz Fen Bilimleri Dergisi 11 (2): 648-62. https://doi.org/10.31466/kfbd.981849.

EndNote

Boylu B, Türkmen M (December 1, 2021) Comparison of KRAS Mutation Status with Clinical Parameters in Colon Adenocarcinoma. Karadeniz Fen Bilimleri Dergisi 11 2 648–662.

IEEE

[1]B. Boylu and M. Türkmen, “Comparison of KRAS Mutation Status with Clinical Parameters in Colon Adenocarcinoma”, KFBD, vol. 11, no. 2, pp. 648–662, Dec. 2021, doi: 10.31466/kfbd.981849.

ISNAD

Boylu, Barış - Türkmen, Mustafa. “Comparison of KRAS Mutation Status With Clinical Parameters in Colon Adenocarcinoma”. Karadeniz Fen Bilimleri Dergisi 11/2 (December 1, 2021): 648-662. https://doi.org/10.31466/kfbd.981849.

JAMA

1.Boylu B, Türkmen M. Comparison of KRAS Mutation Status with Clinical Parameters in Colon Adenocarcinoma. KFBD. 2021;11:648–662.

MLA

Boylu, Barış, and Mustafa Türkmen. “Comparison of KRAS Mutation Status With Clinical Parameters in Colon Adenocarcinoma”. Karadeniz Fen Bilimleri Dergisi, vol. 11, no. 2, Dec. 2021, pp. 648-62, doi:10.31466/kfbd.981849.

Vancouver

1.Barış Boylu, Mustafa Türkmen. Comparison of KRAS Mutation Status with Clinical Parameters in Colon Adenocarcinoma. KFBD. 2021 Dec. 1;11(2):648-62. doi:10.31466/kfbd.981849

The published articles in The Black Sea Journal of Sciences are licensed under Creative Commons Attribution-NonCommercial 4.0 International

Comparison of KRAS Mutation Status with Clinical Parameters in Colon Adenocarcinoma

Abstract

Keywords

Kolon Adenokarsinomlarında KRAS Mutasyon Durumunun Klinik Veriler ile Karşılaştırılması

Abstract

Keywords

References

Details

Primary Language

Subjects

Journal Section

Authors

Publication Date

Submission Date

Acceptance Date

Published in Issue

DOI

IZ

Cite