Epidermal Growth Factor Receptor Status in Circulating Tumor Cells as a Predictive Biomarker of Sensitivity in Castration-Resistant Prostate Cancer Patients Treated with Docetaxel Chemotherapy
Abstract
:1. Introduction
2. Results
2.1. CTC Count
2.2. Baseline CTC Count Correlation with Patient Characteristics
2.3. Analysis of Epidermal Growth Factor Receptor (EGFR) Protein Expression in CTCs
2.4. Multivariate Analyses Indicate that CTCs at Baseline Are an Independent Predictor of Overall Survival
3. Discussion
4. Materials and Methods
4.1. Patient Characteristics
4.2. Drug Administration
4.3. Samples
4.4. Isolation and Enumeration of Circulating Tumor Cells (CTCs—CellSearch System)
4.5. Statistical Analysis
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Variables | N | CTC/7.5 mL | p-Value | |
---|---|---|---|---|
Mean | Range | |||
CTC count at base | 60 | 8 | 0–184 | 0.042 |
PSA (ng/mL) | ||||
<30 | 30 | 2 | 0–3 | 0.021 |
≥30 | 30 | 15 | 0–184 | |
Biopsy Gleason score | ||||
7–8 | 29 | 2 | 0–6 | 0.003 |
9–10 | 31 | 19 | 0–184 | |
EOD | ||||
1–2 | 39 | 1 | 0–14 | 0.034 |
3–4 | 21 | 23 | 0–184 | |
Hemoglobin (g/dL) | ||||
<11.5 | 35 | 18 | 0–184 | 0.059 |
≥11.5 | 25 | 5 | 0–13 | |
Serum albumin (g/dL) | ||||
<3.7 | 28 | 19 | 0–184 | 0.059 |
≥3.7 | 22 | 4 | 0–12 | |
Alkaline phosphatase (IU/L) | ||||
<313 | 21 | 3 | 0–34 | 0.002 |
≥313 | 39 | 18 | 0–184 | |
Lactate dehydrogenase (IU/L) | ||||
<226 | 26 | 2 | 0–18 | 0.066 |
≥226 | 34 | 19 | 0–184 | |
Disease involvement | ||||
Only bone | 42 | 6 | 0–45 | 0.014 |
Bone plus node | 18 | 15 | 0–184 |
Variables | No. | Univariate Analysis | Multivariate Analysis | Hazard Ratio | 95% CI |
---|---|---|---|---|---|
CTC count | |||||
CTC < 5 | 23 | 0.001 | 0.002 | 3.24 | 1.2–4.3 |
CTC ≥ 5 | 37 | ||||
CTC-EGFR | |||||
(−) | 45 | <0.001 | <0.001 | 4.01 | 1.1–6.8 |
(+) | 15 | ||||
PSA (ng/mL) | |||||
<30 | 30 | 0.015 | 0.053 | 4.01 | 1.1–6.8 |
≥30 | 30 | ||||
Biopsy Gleason score | |||||
7–8 | 29 | 0.011 | 0.42 | 1.02 | 0.6–2.9 |
9–10 | 31 | ||||
EOD | |||||
1–2 | 39 | 0.012 | 0.285 | 1.49 | 0.5–6.8 |
3–4 | 21 | ||||
Hemoglobin (g/dL) | |||||
<11.5 | 35 | 0.028 | 0.247 | 1.11 | 0.6–5.6 |
≥11.5 | 25 | ||||
Serum albumin (g/dL) | |||||
<3.7 | 38 | 0.029 | 0.312 | 1.08 | 0.7–5.9 |
≥3.7 | 22 | ||||
Alkaline phosphatase (IU/L) | |||||
<313 | 21 | 0.003 | 0.017 | 2.46 | 1.2-5.3 |
≥313 | 39 | ||||
Lactate dehydrogenase (IU/L) | |||||
<226 | 26 | 0.008 | 0.121 | 1.9 | 0.5–2.9 |
≥226 | 34 | ||||
Disease involvement | |||||
Only bone | 42 | 0.071 | 0.226 | 1.17 | 0.6–2.4 |
Bone plus node | 18 |
No. of Patients | n = 60 |
---|---|
Mean age | 71 (57–82) |
median PSA (ng/mL) | 33.7 (9.4–3241.7) |
≤10.0 | 2 (3.3%) |
10.1–20 | 12 (20.0%) |
20.1–30 | 16 (26.7%) |
30.1–40 | 7 (11.7%) |
40.1–50 | 7 (11.7%) |
50.1–100 | 11 (18.3%) |
≥100.1 | 5 (8.3%) |
Gleason score | |
7 | 8 (13.3%) |
8 | 21 (35.0%) |
9 | 19 (31.7%) |
10 | 12 (20.0%) |
EOD | |
1 | 20 (33.3%) |
2 | 19 (31.7%) |
3 | 13 (21.7%) |
4 | 8 (13.3%) |
Disease involvement | |
Only bone | 32 (53.3%) |
Bone plus node | 28 (46.7%) |
WHO perfomance score | |
0 | 56 (93.3%) |
1 | 4 (6.7%) |
Median Hemoglobin (g/dL) | 10.6 (9.1–12.9) |
Median serum albumin (g/dL) | 3.4 (2.9–4.1) |
Median alkaline phosphatase (IU/L) | 342 (178–561) |
Median lactate dehydrogenase (IU/L) | 265 (189–438) |
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Okegawa, T.; Itaya, N.; Hara, H.; Tambo, M.; Nutahara, K. Epidermal Growth Factor Receptor Status in Circulating Tumor Cells as a Predictive Biomarker of Sensitivity in Castration-Resistant Prostate Cancer Patients Treated with Docetaxel Chemotherapy. Int. J. Mol. Sci. 2016, 17, 2008. https://doi.org/10.3390/ijms17122008
Okegawa T, Itaya N, Hara H, Tambo M, Nutahara K. Epidermal Growth Factor Receptor Status in Circulating Tumor Cells as a Predictive Biomarker of Sensitivity in Castration-Resistant Prostate Cancer Patients Treated with Docetaxel Chemotherapy. International Journal of Molecular Sciences. 2016; 17(12):2008. https://doi.org/10.3390/ijms17122008
Chicago/Turabian StyleOkegawa, Takatsugu, Naoshi Itaya, Hidehiko Hara, Mitsuhiro Tambo, and Kikuo Nutahara. 2016. "Epidermal Growth Factor Receptor Status in Circulating Tumor Cells as a Predictive Biomarker of Sensitivity in Castration-Resistant Prostate Cancer Patients Treated with Docetaxel Chemotherapy" International Journal of Molecular Sciences 17, no. 12: 2008. https://doi.org/10.3390/ijms17122008