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Table 2 Cox proportional hazards analysis of overall survival based on biomarker combination in the discovery cohort

From: Combined impact of lipidomic and genetic aberrations on clinical outcomes in metastatic castration-resistant prostate cancer

 

Variable

Univariable Cox regression

Multivariable Cox regression using AR aberration and 3-lipid signature

Multivariable Cox regression using TP53 aberration and 3-lipid signature

Multivariable Cox regression using RB1 deletion and 3-lipid signature

Multivariable Cox regression using PI3K aberration and 3-lipid signature

HR (95% CI)

P-value

HR (95% CI)

P-value

HR (95% CI)

P-value

HR (95% CI)

P-value

HR (95% CI)

P-value

Biomarker combinations

AR aberration and/or 3-lipid signature (Groups 1 and 2 vs 0)

4.55 (2.27–9.12)

< 0.001

2.89 (1.39–6.00)

0.005

–

–

–

–

–

–

TP53 aberration and/or 3-lipid signature (Groups 1 and 2 vs 0)

5.22 (2.62–10.41)

< 0.001

–

–

3.26 (1.57–6.77)

0.001

–

–

–

–

RB1 deletion and/or 3-lipid signature (Groups 1 and 2 vs 0)

3.05 (1.79–5.20)

< 0.001

–

–

–

–

1.98 (1.12–3.50)

0.019

–

–

PI3K aberration and 3-lipid signature (Group 2 vs 0 and 1)

3.02 (1.75–5.21)

< 0.001

–

–

–

–

–

–

2.15 (1.21–3.82)

0.009

Clinicopatholgic factors

Albumin, g/La

0.86 (0.82–0.91)

< 0.001

0.89 (0.84–0.95)

< 0.001

0.89 (0.84–0.95)

< 0.001

0.89 (0.84–0.95)

< 0.001

0.88 (0.83–0.94)

< 0.001

ECOG performance status (≥ 2 vs 0–1)

3.94 (1.75–8.87)

< 0.001

1.74 (0.73–4.13)

0.212

1.64 (0.69–3.91)

0.263

1.72 (0.72–4.11)

0.222

2.36 (0.98–5.67)

0.054

Pain at baseline (present vs absent)

1.89 (1.12–3.19)

0.018

1.73 (0.99–3.04)

0.056

1.50 (0.86–2.63)

0.152

1.77 (1.01–3.09)

0.046

1.64 (0.93–2.90)

0.089

Haemoglobin (<90 g/L vs ≥ 90 g/L)

2.70 (0.84–8.73)

0.096

–

–

–

–

–

–

–

–

PSA, ng/mLa

1.00 (1.00–1.00)

0.081

–

–

–

–

–

–

–

–

ALP, IU/La

1.00 (1.00–1.00)

0.197

–

–

–

–

–

–

–

–

Treatment type (taxane vs ARSI)

1.05 (0.62–1.79)

0.844

–

–

–

–

–

–

–

–

Treatment line (second line vs first line)

0.87 (0.51–1.48)

0.597

–

–

–

–

–

–

–

–

Visceral metastases (present vs absent)

1.59 (0.75–3.37)

0.225

–

–

–

–

–

–

–

–

ctDNA Fraction

ctDNA fraction > 2%

1.97 (1.06–3.66)

0.032

1.74 (0.91–3.35)

0.097

1.76 (0.93–3.33)

0.083

2.22 (1.17–4.18)

0.014

2.24 (1.18–4.24)

0.014

  1. Univariable and multivariable Cox regression based on biomarker combination, clinicopathologic factors and ctDNA fraction. Only variables with p < 0.05 in univariable analysis were included in multivariable analysis
  2. Group 0 = absence of both 3LS and the genetic aberration; Group 1 = presence of one abnormality (either 3LS or the genetic aberration); Group 2 = presence of both 3LS and the genetic aberration
  3. ALP alkaline phosphatase, ARSI androgen receptor signalling inhibitor, CI confidence interval, ctDNA circulating tumour DNA, ECOG Eastern Cooperative Oncology Group, HR hazard ratio, PI3K phosphatidylinositol-3-kinase, PSA prostate-specific antigen
  4. All p-values < 0.05 are highlighted in bold
  5. aContinuous variable