Incidence of venous thromboembolism in patients with colorectal cancer according to oncogenic status

Ortega, Laura; Alfonso, Pilar; Caballero, Iker Aguilar; Garcia, B.; Anula, Victoria Tirado; Carmena, María de Toro; Alsar, Javier Soto; Alonso, Natalia Gutiérrez; Beránek, M; Jiménez, M. Martín; Martín, Andrés J. Muñoz

doi:10.1007/s12094-020-02339-1

Cited by 9 publications

(7 citation statements)

References 27 publications

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“…Colorectal cancer cells can contribute to a hypercoagulable state of blood through various mechanisms, including tumour procoagulant, which is not present in any normal tissue and can activate coagulation factor X independently of coagulation factor VIII 33 . It has also been reported that p53 and BRAF genes are associated with a hypercoagulable state of blood 34 and that PTEN mutations are associated with increased TF expression, which causes an increase in thrombin expression 25 . Indeed, many oncogenes or tumour suppressor genes and their mutations affect the up- or downregulation of coagulation-associated substance production by tumour cells.…”

Section: Discussionmentioning

confidence: 98%

KRAS-mutant colorectal cancer cell lines cause a prothrombotic state through the upregulation of thrombin: experimental study

Xu,

Liao,

Tan

2023

Annals of Medicine &Amp; Surgery

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Background: The KRAS genotype status is strongly associated with a prothrombotic state in colorectal cancer, and hypercoagulability and cancer-related thrombosis are among the significant events leading to poor prognosis. However, this correlation has not been confirmed at the cellular level. This study aimed to assess the maximum platelet aggregation rate and thrombin expression induced by colorectal cancer cells under different KRAS genotypes. Materials and Methods: Platelet aggregation rate assay and western blotting analysis were used to detect platelet aggregation and thrombin expression induced by four colorectal cancer cells with different KRAS genotypes, including RKO, HCT116, SW480, and SW620. FVIIa/tissue factor and thrombin inhibitors were added to explore changes in platelet aggregation rates induced by colorectal cancer cells and the association between KRAS genotype status and hypercoagulable state. Results: KRAS mutant cells were more likely to increase maximal platelet aggregation, with RKO, HCT116, SW480, and SW620 inducing 34.7%, 55.4%, 44.4%, and 63.8% of platelet aggregation, respectively. The maximum platelet aggregation rate was higher in the metastatic rectal cancer tumor strain SW620 than in the primary rectal cancer strain SW480. RKO cells had lower thrombin expression than the other three cells. Furthermore, the addition of thrombin inhibitors caused a more significant decrease in the platelet aggregation rate in KRAS mutant cell lines compared to KRAS wild-type cell lines. Conclusion: Compared to KRAS wild-type colorectal cancer cells, KRAS mutant colorectal cancer cell lines were more likely to be hypercoagulable through the upregulation of thrombin expression, which was mainly achieved through the TF-thrombin pathway.

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Section: Discussionmentioning

confidence: 98%

KRAS-mutant colorectal cancer cell lines cause a prothrombotic state through the upregulation of thrombin: experimental study

Xu,

Liao,

Tan

2023

Annals of Medicine &Amp; Surgery

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“…However, conflicting evidence exists concerning the connection between KRAS mutation and VTE risk in lung cancer patients, as reported by a positive study 26 and a negative study. 27 In another study, Morán et al 28 performed a retrospective cohort of mCRC patients to analyze the incidence of VTE based on KRAS , NRAS , and BRAF mutations. Patients with KRAS / NRAS mutations exhibited a low incidence of VTE, while those with BRAF mutations showed a high incidence; however, the observed difference did not reach statistical significance, likely due to the limited sample size.…”

Section: Discussionmentioning

confidence: 99%

Estimating Venous Thromboembolism Risk in Metastatic Colorectal Cancer Inpatients: Validation of Existing Risk Scores and Development of New Risk Scores

Qin,

Liang,

Xie

et al. 2023

Clin Appl Thromb Hemost

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Metastatic colorectal cancer (mCRC) patients are predisposed to venous thromboembolism (VTE). This study aimed to (1) evaluate the efficacy of 4 existing cancer-specific VTE models in predicting VTE incidence among hospitalized mCRC patients, and (2) examine the influence of incorporating mCRC molecular subtypes into these models. We conducted an evaluation of 4 cancer-specific VTE models, including Khorana, Vienna CATS, Protecht, and CONKO in a dataset involving 1392 mCRC patients. To evaluate the predictive performance, we utilized receiver operating characteristic (ROC) curves for both the original models and the modified models that incorporated microsatellite instability status or KRAS/ NRAS/ BRAF mutations. Moreover, we computed the net reclassification improvement (NRI) to quantify the enhancements made to the modified VTE risk models. All models demonstrated a moderate area under the ROC curve (ROC-AUC) when predicting the occurrence of VTE: Khorana (0.550), Vienna CATS (0.671), Protecht (0.652), and CONKO (0.578). The incorporation of KRAS and BRAF mutations significantly improved the ROC-AUC of all 4 existing models (modified Khorana: 0.796, modified Vienna CATS: 0.832, modified Protecht: 0.834, and modified CONKO: 0.809). After dichotomizing the risk using a threshold of 3 points and comparing them with the original models, NRI values for the 4 modified models were 0.97, 0.95, 1.11, and 0.98, respectively. All 4 cancer-specific VTE models exhibit moderate performance when identifying mCRC patients at high risk of VTE. Incorporating KRAS and BRAF mutations may enhance the prediction of VTE in hospitalized mCRC patients.

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“…For example, Chang et al reported that 52.9% (9/17) of patients with colorectal cancer harboring the BRAF mutation developed thrombosis, which was significantly more than in those without BRAF mutations (22.4%; 86/383) [ 12 ]. Ortega et al reported that 28.6% (6/21) of patients with colorectal cancer harboring BRAF mutations developed thrombosis, compared with 21.9% (23/105) of those without BRAF mutation [ 13 ] . Although the underlying mechanisms are unknown, the activation of oncogenes induces the expression of genes associated with tissue factors that control hemostasis [ 8 , 12 , 13 , 17 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…Ortega et al reported that 28.6% (6/21) of patients with colorectal cancer harboring BRAF mutations developed thrombosis, compared with 21.9% (23/105) of those without BRAF mutation [ 13 ] . Although the underlying mechanisms are unknown, the activation of oncogenes induces the expression of genes associated with tissue factors that control hemostasis [ 8 , 12 , 13 , 17 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Multiple organ infarction caused by aortic thrombus in a lung cancer patient with the BRAF mutation

Watanabe

Karayama

Inoue

et al. 2022

Respiratory Medicine Case Reports

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Incidence of venous thromboembolism in patients with colorectal cancer according to oncogenic status

Cited by 9 publications

References 27 publications

KRAS-mutant colorectal cancer cell lines cause a prothrombotic state through the upregulation of thrombin: experimental study

KRAS-mutant colorectal cancer cell lines cause a prothrombotic state through the upregulation of thrombin: experimental study

Estimating Venous Thromboembolism Risk in Metastatic Colorectal Cancer Inpatients: Validation of Existing Risk Scores and Development of New Risk Scores

Multiple organ infarction caused by aortic thrombus in a lung cancer patient with the BRAF mutation

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