Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

RAS, BRAF and EGFR Related Genetic Mutations as Predictive Biomarkers in Colorectal Cancer

Adriana Ionescu
ORCID logo ,
Liviu Bilteanu
,
Ovidiu Ionut Geicu
,
Florin Iordache
ORCID logo ,
Loredana Stanca
,
Aurelia Magdalena Pisoschi
ORCID logo ,
Adrian Miron
,
Andreea Iren Serban
* ORCID logo ,
Valentin Calu
ORCID logo
Version 1 : Received: 2 May 2022 / Approved: 5 May 2022 / Online: 5 May 2022 (15:24:14 CEST)

A peer-reviewed article of this Preprint also exists.

Ionescu, A.; Bilteanu, L.; Geicu, O.I.; Iordache, F.; Stanca, L.; Pisoschi, A.M.; Miron, A.; Serban, A.I.; Calu, V. Multivariate Risk Analysis of RAS, BRAF and EGFR Mutations Allelic Frequency and Coexistence as Colorectal Cancer Predictive Biomarkers. Cancers 2022, 14, 2792. Ionescu, A.; Bilteanu, L.; Geicu, O.I.; Iordache, F.; Stanca, L.; Pisoschi, A.M.; Miron, A.; Serban, A.I.; Calu, V. Multivariate Risk Analysis of RAS, BRAF and EGFR Mutations Allelic Frequency and Coexistence as Colorectal Cancer Predictive Biomarkers. Cancers 2022, 14, 2792.

Abstract

Background: Biomarker profiles should represent a coherent description of the colorectal cancer (CRC) stage and its evolution. Methods: Using droplet digital PCR, we detected the allelic frequencies (AF) of KRAS, NRAS, BRAF and EGFR mutations from 60 tumors. We employed a pair-wise association approach to estimate the risk involving AF mutations as outcome variables for clinical data and as predicting variables for tumor-staging. We evaluated correlations between mutations AFs and also between the mutations and histopathology features (tumor staging, inflammation, differentiation and invasiveness). Results: KRAS G12/G13 mutations were present in all patients. KRAS Q61 was significantly associated with poor differentiation, high desmoplastic reaction, invasiveness (ypT4) and metastasis (ypM1). NRAS and BRAF were associated with the right-side localization of tumors. Diabetic patients had a higher risk to exhibit NRAS G12/G13 mutations. BRAF’s presence limited the invasiveness in the submucosa, co-existing with NRAS G12/G13 mutations. Conclusions: The associations we found and the mutational AF we reported may help to understand disease processes and may be considered as potential CCR biomarker candidates. In addition, we propose representative mutation panels associated with specific clinical and histopathological features of CRC, as a unique opportunity to refine the degree of personalization of CRC treatment.

Keywords

Colorectal cancer; ddPCR; KRAS; NRAS; BRAF; EGFR

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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