Abstract
PIM-1 is an oncogene involved in cell cycle progression, cell growth, cell survival and therapy resistance, activated in many types of cancer, and is now considered as a very promising target for cancer therapy. We report for the first time that PIM-1 is overexpressed in circulating tumor cells (CTCs) from metastatic castration-resistant prostate cancer patients (mCRPC). We first developed and validated a highly sensitive RT-qPCR assay for quantification of PIM-1 transcripts. We further applied this assay to study PIM-1 expression in EpCAM(+) CTC fraction isolated from 64 peripheral blood samples of 50 mCRPC patients. CTC enumeration in all samples was performed using the FDA-cleared CellSearch® system. PIM-1 overexpression was detected in 24/64 (37.5%) cases, while in 20/24 (83.3%) cases that were positive for PIM-1 expression, at least one CTC/7.5 mL PB was detected in the CellSearch®. Our data indicate that PIM-1 overexpression is observed at high frequency in CTCs from mCRPC patients and this finding, in combination with androgen receptor splice variant 7 (AR-V7) expression in CTCs, suggest its potential role as a very promising target for cancer therapy. We strongly believe that PIM-1 overexpression in EpCAM(+) CTC fraction merits to be further evaluated and validated as a non-invasive circulating tumor biomarker in a large and well-defined patient cohort with mCRPC.
Highlights
Prostate cancer (PCa) is the second most common cancer in men worldwide, with an estimated global incidence of 1.3 million cases in 2018 [1]
We have recently developed and validated a multiplex RT-qPCR assay for androgen receptor (AR) splice variants and have shown that the androgen receptor splice variant 7 (AR-V7) splice variant is highly overexpressed in circulating tumor cells (CTCs) of patients with metastatic castration-resistant prostate cancer (mCRPC) [16]
We further evaluated for the first time whether PIM-1 overexpression in EpCAM(+) CTC fraction is correlated with AR-V7 expression in the same samples
Summary
Prostate cancer (PCa) is the second most common cancer in men worldwide, with an estimated global incidence of 1.3 million cases in 2018 [1]. We have recently developed and validated a multiplex RT-qPCR assay for AR splice variants and have shown that the AR-V7 splice variant is highly overexpressed in CTCs of patients with mCRPC [16]. PIM-1 expression has been shown to be increased in prostate tissue demonstrating partial response to docetaxel, suggesting the predictive role of PIM-1 to this type of treatment [28]. We first developed and validated a highly sensitive RT-qPCR assay for quantification of PIM-1 transcripts and reported for the first time that PIM-1 is overexpressed in EpCAM(+) CTC fraction isolated from mCRPC patients. Our data indicate that PIM-1 overexpression in CTCs should be prospectively evaluated as a potential biomarker for prostate cancer management in a large and well-defined patient cohort
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