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Table 3 Pathway analysis and principal components analysis (PCA) for the association between chemical sub-classes of serum metabolites and prostate cancer-specific mortality in the ATBC Study a

From: Metabolomic profile of prostate cancer-specific survival among 1812 Finnish men

Chemical sub-class pathway

Pathway analysis

PCA analysis for pattern score (by quartiles) b

No. of contributing metabolites

P-value

Q1

Q2

Q3

Q4

P-value c

Referent

HR (95% CI)

HR (95% CI)

HR (95% CI)

Endocannabinoids

10

<10−5

1.00

1.25 (0.94, 1.67)

1.54 (1.16, 2.04)

1.92 (1.46, 2.51)

4.5×10−7

Glycine, serine, and threonine metabolism

10

<10−5

1.00

1.22 (0.92, 1.63)

1.43 (1.08, 1.88)

1.92 (1.47, 2.51)

6.5×10−7

Gamma-glutamyl amino acids

18

<10−5

1.00

1.30 (0.97, 1.72)

1.26 (0.94, 1.69)

1.94 (1.49, 2.52)

9.5×10−7

Glutamate metabolism

13

<10−5

1.00

1.14 (0.87, 1.51)

1.39 (1.05, 1.83)

1.71 (1.32, 2.23)

1.5×10−5

Eicosanoid

3

<10−5

1.00

0.93 (0.70, 1.25)

1.22 (0.93, 1.60)

1.62 (1.25, 2.10)

1.8×10−5

Sphingolipid synthesis

3

<10−5

1.00

1.08 (0.81, 1.44)

1.36 (1.03, 1.78)

1.61 (1.24, 2.08)

5.5×10−5

Glutathione metabolism

7

<10−5

1.00

0.59 (0.46, 0.75)

0.63 (0.49, 0.80)

0.62 (0.48, 0.79)

1.7×10−4

Dipeptides

6

<10−5

1.00

1.17 (0.87, 1.56)

1.08 (0.81, 1.45)

1.65 (1.27, 2.15)

2.0×10−4

  1. Abbreviations: HR hazard ratio, CI confidence interval, ATBC Alpha-Tocopherol, Beta-Carotene Cancer Prevention
  2. a Pathway analysis: We examined the association between 95 chemical sub-classes of serum metabolites and prostate cancer-specific mortality and tested a single P-value for pathways using a parametric bootstrap method. Within each bootstrap replication, P-values were generated from a vector of score test statistics from an estimated covariance matrix with a multivariate normal distribution (mean=0). The pathway P-values are calculated based on 100,000 permutations
  3. b Models were adjusted for age at baseline, age at diagnosis, cancer stage at diagnosis (stage I–IV), and Gleason scores at cancer diagnosis
  4. c Bonferroni-corrected threshold = 5.3×10−4, 0.05/95