Purpose: Unlike cetuximab, there is a paucity of biomarkers for bevacizumab as predictors of outcome in metastatic colorectal cancer (mCRC) patients. Obviously exploring the worth of some potential markers in this setting is warranted. The purpose of this study was to investigate the predictive value of the presence of K-RAS and B-RAF mutations on the outcome of patients with mCRC treated with FOLFIRI and bevacizumab combination therapy.
Methods: A total of 172 patients with mCRC were evaluated. K-RAS and B-RAF mutations were analyzed by quantitative PCR. Median progression-free survival (PFS) and overall survival (OS) were compared utilizing chi-square and Mann-Whitney U tests, respectively.
Results: Forty-four percent (N=77) of the patients were found to harbor K-RAS mutations and 6 (7.5%) were positive for B-RAF mutations. In baseline no difference in PFS and OS was observed between the groups with or without K-RAS mutation. No relationship was established between K-RAS and B-RAF mutation status and baseline CEA and CA19-9 tumor markers levels.
Conclusion: K-RAS and B-RAF mutations do not seem to be predictive of treatment outcome as potential biomarkers for bevacizumab therapy in mCRC. However, not only the presence of K-RAS and B-RAF mutations but also the different biological behavior of the various subtypes of mutations should be considered as potential determinants in the final outcome of this disease.
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Curr Issues Mol Biol
November 2024
Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 19 Jordana, 41-808 Zabrze, Poland.
SIGLEC9 (sialic acid-binding Ig-like lectin 9) is a molecule thought to have a significant influence on the immune properties of the colorectal cancer (CRC) tumor microenvironment (TME). In our study, we assessed the expression of the SIGLEC9 protein in CRC tissue and the surgical margin tissue. Using RT-PCR, we analyzed mutations in the KRAS, NRAS, BRAF, PIK3CA, and AKT genes.
View Article and Find Full Text PDFCurr Issues Mol Biol
September 2024
Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 19 Jordana, 41-808 Zabrze, Poland.
Dis Colon Rectum
January 2025
Department of Pathology, West China Hospital, Sichuan University, Chengdu, China.
Background: Scant data are available on heterogenous staining of mismatch repair protein in colorectal cancer.
Objective: This study aimed to improve insights into clinicopathologic features and prognosis of colorectal cancer harboring heterogenous mismatch repair protein staining.
Design: A single-center retrospective observational study.
Cancer Lett
April 2024
Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Electronic address:
Inhibition of K-RAS effectors like B-RAF or MEK1/2 is accompanied by treatment resistance in cancer patients via re-activation of PI3K and Wnt signaling. We hypothesized that myotubularin-related-protein-7 (MTMR7), which inhibits PI3K and ERK1/2 signaling downstream of RAS, directly targets RAS and thereby prevents resistance. Using cell and structural biology combined with animal studies, we show that MTMR7 binds and inhibits RAS at cellular membranes.
View Article and Find Full Text PDFJ Proteome Res
February 2024
Institute for Research in Immunology and Cancer (IRIC) Université de Montréal, Montréal H3T 1J4, Canada.
Identification of K-Ras and B-Raf mutations in colorectal cancer (CRC) is essential to predict patients' response to anti-EGFR therapy and formulate appropriate therapeutic strategies to improve prognosis and survival. Here, we combined parallel reaction monitoring (PRM) with high-field asymmetric waveform ion mobility (FAIMS) to enhance mass spectrometry sensitivity and improve the identification of low-abundance K-Ras and B-Raf mutations in biological samples without immunoaffinity enrichment. In targeted LC-MS/MS analyses, FAIMS reduced the occurrence of interfering ions and enhanced precursor ion purity, resulting in a 3-fold improvement in the detection limit for K-Ras and B-Raf mutated peptides.
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