Recent Updates on the Significance of KRAS Mutations in Colorectal Cancer Biology

László, Loretta; Kurilla, Anita; Takács, Tamás; Kudlik, Gyöngyi; Koprivanacz, Kitti; Buday, László; Vas, Virag

doi:10.3390/cells10030667

Cited by 28 publications

(20 citation statements)

References 133 publications

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“…The CRC incidence rate is highly correlated with age; for those who tend to have a high risk of sporadic CRCs, they have a high likelihood of being late-onset cases, but with a high probability of having MSI (microsatellite instability), MLH1 methylated, BRAF, and KARS mutation [ 34 ]. Some studies also demonstrated the mutation associated with advanced and metastasis CRCs [ 35 ]. Based on the meta-analysis evidence, these biomarkers also play important roles for the clinical treatment of targeted therapy designed by epidermal growth factor receptor (EGFR) signaling [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Enhancing Prediction Performance by Add-On Combining Circulating Tumor Cell Count, CD45neg EpCAMneg Cell Count on Colorectal Cancer, Advance, and Metastasis

Chiu

Hsieh

You

et al. 2021

Cancers

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Conventional circulating tumor cell (CTC) enumeration could ignore the CTCs more relevant to cancer metastasis. Thus, negative selection CTC enumeration was proposed, by which information on two cellular biomarkers (numbers of CTCs and CD45neg EpCAMneg cells) can be obtained. By combining this approach with the conventional biomarker carcinoembryonic antigen (CEA), this study aimed to explore whether any combination of these biomarkers could improve the predictive performance for colorectal cancer (CRC) or its status. In this work, these two cell populations in healthy donors and CRC patients were quantified. Results revealed that enumeration of these two cell populations was able to discriminate healthy donors from CRC patients, even patients with non-advanced CRC. Moreover, the combination of the two cell populations showed improved performance (AUROC: 0.893) for CRC prediction over the use of only one population. Compared with CEA alone, the combination of the three biomarkers increased the performance (AUROC) for advanced CRC prediction from 0.643 to 0.727. Compared with that of CEA alone for metastatic CRC prediction, the AUROC was increased from 0.780 to 0.837 when the CTC count was included. Overall, this study demonstrated that the combination of these two cellular biomarkers with CEA improved the predictive performance for CRC and its status.

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Section: Discussionmentioning

confidence: 99%

Enhancing Prediction Performance by Add-On Combining Circulating Tumor Cell Count, CD45neg EpCAMneg Cell Count on Colorectal Cancer, Advance, and Metastasis

Chiu

Hsieh

You

et al. 2021

Cancers

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“…Statistical analysis results of variables in this study are provided in Table 4. Moreover, we have determined that there is statistically significant correlation between grade and KRAS mutation status (p=0.0859770) and age group versus KRAS mutation type (p= 0.0814710) when type one error is taken as 0,1. of cells as a result of accumulation of various activating mutations, loss of function of tumor suppressor proteins and activation of proto-oncogenic proteins like KRAS (László et al, 2021).…”

Section: Findings and Discussionmentioning

confidence: 99%

Kolon Adenokarsinomlarında KRAS Mutasyon Durumunun Klinik Veriler ile Karşılaştırılması

BOYLU

Türkmen

2021

Karadeniz Fen Bilimleri Dergisi

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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.

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“…For example, blocking EGFR signaling by an antibody therapy in CRC is inefficient in patients with mutated KRAS tumors, which provide a stimulatory signal downstream of EGFR. In-depth analysis of individual CTCs from patients with CRC revealed the striking heterogeneity of KRAS status within and between patients [53,54], and the occurrence and concordance of these mutations in metastatic CRC may vary between primary tumors, CTCs, and metastatic tumors [54][55][56]. When KRAS mutations in CTCs from patients with metastatic CRC were examined throughout disease progression and compared with their corresponding primary tumors, CTCs had different KRAS mutations during treatment [57].…”

Section: Molecular and Functional Characterization Of Ctcsmentioning

confidence: 99%

Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as a Liquid Biopsy Marker in Colorectal Cancer

Heidrich

Abdalla

Reeh

et al. 2021

Cancers

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Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. It is a heterogeneous tumor with a wide genomic instability, leading to tumor recurrence, distant metastasis, and therapy resistance. Therefore, adjunct non-invasive tools are urgently needed to help the current classical staging systems for more accurate prognostication and guiding personalized therapy. In recent decades, there has been an increasing interest in the diagnostic, prognostic, and predictive value of circulating cancer-derived material in CRC. Liquid biopsies provide direct non-invasive access to tumor material, which is shed into the circulation; this enables the analysis of circulating tumor cells (CTC) and genomic components such as circulating free DNA (cfDNA), which could provide the key for personalized therapy. Liquid biopsy (LB) allows for the identification of patients with a high risk for disease progression after curative surgery, as well as longitudinal monitoring for disease progression and therapy response. Here, we will review the most recent studies on CRC, demonstrating the clinical potential and utility of CTCs and ctDNA. We will discuss some of the advantages and limitations of LBs and the future perspectives in the field of CRC management.

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Recent Updates on the Significance of KRAS Mutations in Colorectal Cancer Biology

Cited by 28 publications

References 133 publications

Enhancing Prediction Performance by Add-On Combining Circulating Tumor Cell Count, CD45neg EpCAMneg Cell Count on Colorectal Cancer, Advance, and Metastasis

Enhancing Prediction Performance by Add-On Combining Circulating Tumor Cell Count, CD45neg EpCAMneg Cell Count on Colorectal Cancer, Advance, and Metastasis

Kolon Adenokarsinomlarında KRAS Mutasyon Durumunun Klinik Veriler ile Karşılaştırılması

Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as a Liquid Biopsy Marker in Colorectal Cancer

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