Researchers have reported EGFR overexpression as a stable marker for prostate cancer dissemination to rigid organs, preferentially bones.
Prostate cancer is the second most frequent malignancy in men worldwide. The 5-year survival rate in patients with localised prostate cancer is nearly 100%. However, for patients with metastatic disease the cancer is incurable. As a result, there is an urgent need for markers that can help clinicians detect initial stages of tumour dissemination, determine likelihood of recurrence and predict preferential sites of metastasis. This in turn will help personalise patient treatment and prolong patient survival.
Epithelial-mesenchymal transition (EMT) and plasticity are key in metastatic progression. Researchers suggest that the epidermal growth factor receptor (EGFR) is key in prostate tumorigenesis and progression. Evidence has shown that EGFR expression associates with high grade advanced stage prostate cancer, as well as high risk for prostate-specific antigen (PSA) recurrence and bone metastases. However, there is a lack of complex study exploring EGFR expression in prostate cancer within the context of tumour characteristics and dissemination.
Therefore, in this study published in the British Journal of Cancer, researchers assessed the expression of EGFR protein in the dissemination cascade. The team tracked EGFR overexpression in 1,039 primary tumours, circulating tumour cells from 39 risk patients and metastatic samples from 21 castration-resistant prostate cancer cases. They also compared it to clinical parameters and multiple molecular factors (e.g. EMT-related proteins) to determine its feasibility as a stable marker.
A stable marker
The team found that 14% of primary tumours overexpressed EGFR. In these cases, it associated with shorter metastasis-free survival and was an independent indicator of worse over survival. Overexpression of EGFR correlated with pro-migratory and pro-metastatic phenotype of tumour cells. These tumours also had higher collagen fibre content which influences cell migration, invasiveness and proliferation. This is also indicative of a worse prognosis. Researchers also found that all circulating tumour cells (detected in 13% of cases) were positive for EGFR. This was independent of their EMT-related phenotype. In castration-resistant bone metastases (29% of patients), EGFR expression was more prevalent. This suggests that organ-specific factors, including stiffness and tumour microenvironment, may regulate harbouring of EGFR-positive tumour cells.
To summarise, the team found EGFR overexpression in both primary tumour and circulating tumour cells – an indicator of poor prognosis. This data demonstrates that EGFR overexpression may be a suitable candidate biomarker, independent of EMT, of prostate cancer dissemination cascade.
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