Clinical, Pathological and Molecular Insights on KRAS, NRAS, BRAF, PIK3CA and TP53 Mutations in Metastatic Colorectal Cancer Patients from Northeastern Romania

Afrăsânie, Vlad-Adrian; Marinca, Mihai Vasile; Gafton, Bogdan; Alexa-Stratulat, Teodora; Rusu, Alexandra; Froicu, E.; Sur, Daniel; Lungulescu, Cristian Virgil; Popovici, Larisa; Lefter, Andrei-Vlad; Afrăsânie, Irina; Ivanov, Anca; Miron, Lucian; Rusu, Cristina

doi:10.3390/ijms241612679

Cited by 5 publications

(4 citation statements)

References 37 publications

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“…Since colorectal cancers with KRAS mutations are a heterogeneous group, the frequency of these mutations can also vary among different populations. In our study, the prevalence rate of KRAS mutation was 44.93%, which is similar to data reported for populations in Slovenia (48.8%) [18], Germany (41%) [19], Turkey (44%, 41.9%, and 47.6%) [20][21][22], Italy (43%, 47%) [23][24][25], Russia (49.5%) [26], and Romania (45.2%) [27]. Some of these countries are geographically close to our location.…”

Section: Discussionsupporting

confidence: 89%

KRAS Mutation Status in Bulgarian Patients with Advanced and Metastatic Colorectal Cancer

Radanova

Mihaylova

Stoyanov

et al. 2023

IJMS

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RAS somatic variants are predictors of resistance to anti-EGFR therapy for colorectal cancer (CRC) and affect the outcome of the disease. Our study aimed to evaluate the frequency of RAS, with a focus on KRAS variants, and their association with tumor location and some clinicopathological characteristics in Bulgarian CRC patients. We prospectively investigated 236 patients with advanced and metastatic CRC. Genomic DNA was extracted from FFPE tumor tissue samples, and commercially available kits were used to detect RAS gene somatic mutations via real-time PCR. A total of 115 (48.73%) patients tested positive for RAS mutations, with 106 (44.92%) testing positive for KRAS mutations. The most common mutation in exon 2 was c.35G>T p.Gly12Val (32.56%). We did not find a significant difference in KRAS mutation frequency according to tumor location. However, patients with a mutation in exon 4 of KRAS were 3.23 times more likely to have a tumor in the rectum than in other locations (95% CI: 1.19–8.72, p = 0.021). Studying the link between tumor location and KRAS mutations in exon 4 is crucial for better characterizing CRC patients. Further research with larger cohorts, especially in rectal cancer patients, could provide valuable insights for patient follow-up and treatment selection.

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Section: Discussionsupporting

confidence: 89%

KRAS Mutation Status in Bulgarian Patients with Advanced and Metastatic Colorectal Cancer

Radanova

Mihaylova

Stoyanov

et al. 2023

IJMS

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“…It is well known that TP53 nuclear over expression is detected in ~70-90% of solid malignancies characterized by different histo-genetic origins (23,24). Molecular analyses based on TP53 and other genesincluding the K-RAS oncogene -have revealed simultaneous mutations that affect these genetic markers in specific populations (25,26). Besides K-RAS/TP53 mutations, multigene mutations in colon carcinoma patients create specific genetic signatures that modify the corresponding response levels to targeted therapeutic regimens (27,28).…”

Section: Discussionmentioning

confidence: 99%

Comparative Expression Analysis of TP53 Tumor Suppressor and MDM2 Oncogene in Colorectal Adenocarcinoma

NIOTIS,

DIMITROULIS,

SPYROPOULOU

et al. 2024

CDP

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Background/Aim: The tumor protein 53 (TP53) tumor suppressor protein (17p13.1) acts as a significant regulator for the cell cycle normal function. The gene is frequently mutated in colorectal adenocarcinoma (CRC) patients and is associated to poor prognosis and low response rates to chemo-targeted therapy. Our purpose was to correlate TP53 expression with Mouse Double Minute 2 Homolog (MDM2), a proto-oncogene (12q14.3) and a major negative regulator in the TP53-MDM2 auto-regulatory pathway. Materials and Methods: A total of forty (n=40) colorectal adenocarcinoma (CRC) cases were included in this study. An immunohistochemistry-based assay was implemented by using anti-TP53 and anti-MDM2 antibodies in the corresponding tissue sections. Additionally, a digital image analysis assay was implemented for objectively measuring TP53/MDM2 immunostaining intensity levels. Results: TP53 protein overexpression was detected in 27/40 (67.5%), whereas MDM2 overexpression in 28/40 (70%) cases. Interestingly, in 21/40 (52.5%) cases, a combined TP53/MDM2 co-expression was detected, whereas in 6/40 (15%), a combined loss of expression was identified (overall co-expression: p=0.119). p53 overexpression was significantly correlated to grade of the examined cases (p=0.001), whereas MDM2 to stage and max diameter of the malignancies (p=0.001 and 0.024, respectively). Conclusion: TP53/MDM2 over expression is a frequent and significant genetic event in CRCs associated with an aggressive biological behavior, as a result of increased dedifferentiation grade and advanced stage/elevated tumor volume, respectively. MDM2 oncogene overactivation combined with mutated and overexpressed TP53 is observed in sub-groups of patients leading to specific gene/protein signatures – targets for personalized chemotherapeutic approaches.

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“…It is also necessary to increase screening for the disease in young people and to raise the attention of clinicians to the increased incidence of CRC in young patients ( 50 ). In addition, attention has been paid to the phenomenon of genetic variability specific to the Romanian population, with studies on KRAS, NRAS, BRAF, PIK3CA, and TP53 Mutations ( 51 ). However, the exact mechanism remains unclear and further in-depth studies on the causes of the high incidence of CRC in Romania are highly relevant.…”

Section: Discussionmentioning

confidence: 99%

Long-term trends in the burden of colorectal cancer in Europe over three decades: a joinpoint regression and age-period-cohort analysis

Long,

Mao,

Zhang

et al. 2023

Front. Oncol.

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BackgroundThe burden of colorectal cancer (CRC) in Europe is at a high level, but the epidemiological features have not yet been systematically studied. This study aimed to provide a timely and reliable assessment of the burden and trends of CRC in Europe to provide a scientific basis for its prevention and treatment.MethodsWe analyzed data on CRC in 44 European countries between 1990 and 2019 from the Global Burden of Disease study (GBD) 2019. In addition, the joinpoint regression model was applied to reflect temporal trends. The age-period-cohort model was constructed to explore age, period, and birth cohort effects that influence the risk of morbidity and mortality.ResultsIn Europe, new cases, disability-adjusted life years (DALYs) and deaths of CRC rose by 70.01%, 22.88% and 38.04% from 1990 to 2019, respectively. The age-standardized incidence rate (ASIR) has increased, while age-standardized DALY rate and age-standardized mortality rate (ASMR) have declined. We found that men experienced a significantly higher CRC burden than women. Age-period-cohort analysis showed that the risk of incidence and mortality increased with age and time; and it was lower in the later-born cohort than the earlier-born cohort.ConclusionASIR for CRC in Europe generally trended upwards from 1990 to 2019, stabilizing in recent years but still at a high level. CRC burden varied considerably in different countries. There was a pronounced gender difference in CRC burden, and middle-aged and older men should be a priority population for CRC prevention and treatment.

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Clinical, Pathological and Molecular Insights on KRAS, NRAS, BRAF, PIK3CA and TP53 Mutations in Metastatic Colorectal Cancer Patients from Northeastern Romania

Cited by 5 publications

References 37 publications

KRAS Mutation Status in Bulgarian Patients with Advanced and Metastatic Colorectal Cancer

KRAS Mutation Status in Bulgarian Patients with Advanced and Metastatic Colorectal Cancer

Comparative Expression Analysis of TP53 Tumor Suppressor and MDM2 Oncogene in Colorectal Adenocarcinoma

Long-term trends in the burden of colorectal cancer in Europe over three decades: a joinpoint regression and age-period-cohort analysis

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