Serum Adipokines as Predictors for the Outcome of Prostate Biopsies at Early Stage Prostate Cancer Diagnosis

Figures & data

Figure 1 Diagram representing a common trajectory in men who are candidates for prostate biopsy based on PSA or prior history of prostate cancer.

Abbreviations: PSA, prostate-specific antigen, PCa, prostate cancer, REDUCE, Reduction by Dutasteride of Prostate Cancer Events, DRE, digital rectal exam, AS, active surveillance.

Table 1 Clinical Characteristics and Serum Adipokine Values in the Three Cohorts

Variable	GU Biobank Cohort	REDUCE Cohort	AS Cohort
Number of patients	1061	1209	154
Patient’s Characteristics
Age, (yr)
Median (IQR)	61.8 (55.6–67.3)	65.0 (60.0–69.0)	65.4 (60.0–69.6)
PSA (ng/mL)
Median (range)	5.3 (0.0–165.2)	5.9 (0.6–122.4)	4.7 (0.4–17.6)
Digital rectal exam
Normal (%)	763 (71.9)	1168 (96.6)	143 (93)
Abnormal (%)	295 (27.8)	41 (3.4)	11 (7)
Prostate volume (mL)
Median (range)	40.0 (5.0–204.0)	44.3 (7.7–171.5)	45.0 (11.0–125.0)
BMI
Median (IQR)	26.6 (24.4–29.4)	27.0 (24.7–29.6)	27.0 (25.05–28.55)
Family history (%)
Positive	19.0	11.8	25
Negative	76.0	88.2	75
Adipokines
IL-6 (pg/mL)
Median (IQR)	2.5 (1.3–4.7)	2.9 (1.5–5.3)	(1.0–3.2)
Range	0.0–192.4	0.0–1157.2	0.0–64.1
TNF-alpha (pg/mL)
Median (IQR)	4.9 (3.6–6.7)	4.1 (2.8–5.5)	4.5 (3.3–5.7)
Range	0.1–64.3	0.0–258.6	0.0–21.9
HGF (ng/mL)
Median (IQR)	688.9 (430.2–1003.5)	501.9 (306.4–770.8)	411.6 (250.3–718.8)
Range	1.2–8940.8	0.0–16,717.4	0.2–3322.4
MCP-1 (pg/mL)
Median (IQR)	312.9 (229.5–406.2)	266.3(186.8–377.0)	246.9(157.7–328.6)
Range	15.3–1488.8	0.0–1999.5	1.8–988.6
NGF (pg/mL)
Median (IQR)	4.4(2.2–7.6)	4.4(2.9–6.4)	2.9(1.8–4.3)
Range	0.1–461.2	0.0–3020.8	0.0–83.5
Resistin (ng/mL)
Median (IQR)	12,875.0 (9502.0–17,288.2)	21,814.3 (15,902.9–30,389.6)	15,706.4 (10,477.5–22,189.2)
Range	1.3–75,895.2	0.0–332,705.6	2729.8–61,050.9

Abbreviations: PSA, prostate-specific antigen; BMI, body mass index; IL, interleukin; TNF, tumor necrosis factor; HGF, hepatocyte growth factor; MCP, monocyte chemoattractant protein; NGF, nerve growth factor; IQR, interquartile range; GU, genitourinary; AS, active surveillance.

Table 2 Multivariable Analysis – Adipokines as Predictors of Low-Risk/No Risk Prostate Cancer in the UHN GU Biobank Cohort (Biopsy Naïve) Adjusted for Clinical Variables

Variable	Continuous/Reference Group	OR	95% CI of OR		P value
Age	Continuous	1.03	1.01	1.04	0.007
PSA (log)	Continuous	3.06	2.35	3.99	<0.001
DRE* (N vs Y)	Normal	3.51	2.55	4.84	<0.001
Family history (N vs Y)	Negative	1.50	1.05	2.16	0.03
Ethnicity					0.03
African vs Europeans	Europeans	1.15	0.61	2.15	0.7
Other (2–5) vs Europeans		1.70	1.14	2.53	0.01
IL-6	Continuous	1.13	1.00	1.28	0.05

Notes: AUC: 0.756. Out-of-sample AUC: 0.751. MSE: 0.183, AIC: 1094.0. *Positive DRE. ORs of continuous variables were calculated using one-unit increasing.

Abbreviations: PSA, prostate-specific antigen; DRE, digital rectal exam; IL, interleukin; AIC, Akaike information criterion; AUC, area under the curve; OR, odd’s ratio; N, no; Y, yes.

Table 3 Multivariable Analysis – Adipokines (IL-6, NGF) as Predictors of Low -Risk/No Risk Prostate Cancer in the REDUCE Trial Cohort Adjusted for Clinical Variables

Variable	Continuous/Reference Group	OR	95% CI of OR		P Value
Age at 2yr Biopsy	Continuous	0.94	0.90	0.98	0.008
DRE					0.10
Abnormal, no change	Normal	2.92	0.35	24.25	0.30
Abnormal, changed	Normal	0.26	0.05	1.26	0.01
Log (Present PSA)	Continuous	0.52	0.26	1.02	0.06
Log (PSA) Change	Continuous	0.65	0.30	1.42	0.30
Prior History of HGPIN: Yes	No	0.30	0.16	0.543	<0.001
Number of Cores at Baseline Biopsy	Continuous	1.16	1.04	1.30	0.009
Prostate Volume	Continuous	1.03	1.01	1.050	0<0.001
IL-6	Continuous	1.02	0.99	1.07	0.20
NGF	Continuous	1.00	0.98	1.03	0.80

Notes: AUC: 0.780. Out-of-sample AUC: 0.778. MSE: 0.057, AIC: 516.8. ORs of continuous variables were calculated using one unit increasing. Clinical variables: age, DRE, Log PSA, Log PSA change, history of HGPIN, number of biopsy cores and prostate volume.

Abbreviations: PSA, prostate-specific antigen; DRE, digital rectal exam; IL, interleukin; AIC, Akaike information criterion; AUC, area under the curve; OR, odd’s ratio; HGPIN, high grade prostatic intraepithelial neoplasia; MSE, mean squared error.

Table 4 Multivariable Analysis – Adipokine (MCP-1) as Predictor of Low-Risk/No Risk Prostate Cancer in the AS Cohort Adjusted for Clinical Variables

Variable	Continuous/Reference Group	OR	95% CI of OR		P value
Present PSA	Continuous	0.78	0.67	0.92	0.003
Number of Positive Cores at Baseline Biopsy	Continuous	0.49	0.26	0.94	0.03
Prostate Volume	Continuous	1.04	1.01	1.07	0.016
Digital Rectal Exam: Abnormal	Normal	0.15	0.03	0.85	0.03
MCP-1	Continuous	1.00	0.99	1.00	0.03

Notes: AUC: 0.812. Out-of-sample AUC: 0.779. MSE: 0.148, AIC: 124.6. ORs of continuous variables were calculated using one unit increasing. Clinical variables: DRE, PSA, number of biopsy cores and prostate volume.

Abbreviations: PSA, prostate-specific antigen; DRE, digital rectal exam; MCP, monocyte chemoattractant protein; AIC, Akaike information criterion; AUC, area under the curve; OR, odd’s ratio; MSE, mean squared error.

Table 5 Multivariable Analysis – Adipokine (Resistin) as Predictor of Low-Risk/No Risk Prostate Cancer in the AS Cohort Adjusted for Clinical Variables

Variable	Continuous/Reference Group	OR	95% CI of OR		P value
Present PSA	Continuous	0.81	0.68	0.96	0.01
Number of Cores Taken on Baseline Biopsy	Continuous	1.33	1.12	1.59	0.001
Number of Positive Cores at Baseline Biopsy	Continuous	0.47	0.25	0.88	0.02
Prostate Volume	Continuous	1.02	1.00	1.05	0.08
DRE: Abnormal	Normal	0.10	0.02	0.59	0.01
Resistin	Continuous	1.00	1.00	1.00	0.008

Notes: AUC: 0.816. Out-of-sample AUC: 0.766. MSE: 0.182, AIC: 146.2. ORs of continuous variables were calculated using one unit increasing. Clinical variables: DRE, PSA, number of biopsy cores and prostate volume.

Abbreviations: PSA, prostate-specific antigen; DRE, digital rectal exam; AIC, Akaike information criterion; AUC, area under the curve; OR, odd’s ratio; MSE, mean squared error.