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Blood metabolites as predictors of skin cancer risk: a comprehensive analysis

Kaymin Wu

Kaymin Wu

The First People’s Hospital of Hangzhou Linping District: Zhejiang University School of Medicine Second Affiliated Hospital Linping HospitalHang Zhou, China
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Wu, Kaymin
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Youwu He

Youwu He

The First People’s Hospital of Hangzhou Linping District: Zhejiang University School of Medicine Second Affiliated Hospital Linping HospitalHang Zhou, China
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He, Youwu
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Ailian Hua

Ailian Hua

The First People’s Hospital of Hangzhou Linping District: Zhejiang University School of Medicine Second Affiliated Hospital Linping HospitalHang Zhou, China
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Hua, Ailian
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Yi Yao

Yi Yao

The First People’s Hospital of Hangzhou Linping District: Zhejiang University School of Medicine Second Affiliated Hospital Linping HospitalHang Zhou, China
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Yao, Yi
  
19 août 2024
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Catégorie d'article: Original Study
Publié en ligne: 19 août 2024
Pages: 74 - 85
Reçu: 14 févr. 2024
Accepté: 19 juin 2024
DOI: https://doi.org/10.2478/ahem-2004-0007
Mots clés
© 2024 Kaymin Wu et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Figure 1.

Selection workflow
Selection workflow

Figure 2.

Scatter plot of 1-arachidonylglycerol
Scatter plot of 1-arachidonylglycerol

Figure S1.

Forrest plot of Plasma metabolites significantly associated with skin cancer (IVW)
Forrest plot of Plasma metabolites significantly associated with skin cancer (IVW)

Metabolites with significant pleiotropy

Metabolites Methods P
X-12117 Egger Intercept 0.043
X-13695 Egger Intercept 0.049
Oleoyl-linoleoyl-glycerol (18:1 to 18:2) [2] / linoleoyl-arachidonoyl-glycerol (18:2 to 20:4) [2] Egger Intercept 0.024
Adenosine 5′-diphosphate (ADP) / cytidine Egger Intercept 0.025
Caffeine / linoleate (18:2n6) Egger Intercept 0.047
Gamma-glutamylthreonine Global Test <0.001
Picolinoylglycine Global Test <0.001
Hydroxypalmitoyl sphingomyelin (d18:1/16:0(OH)) Global Test 0.012
Cysteinylglycine Global Test 0.017
Hypotaurine Global Test 0.011
Cortisone / 4-cholesten-3-one Global Test 0.029
Hypotaurine / cysteine Global Test 0.003
Retinol (Vitamin A) / linoleoyl-arachidonoyl-glycerol (18:2 to 20:4) [2] Global Test 0.011

Plasma metabolites significantly associated with skin cancer

id Metabolites pvalue
GCST90199649 1-stearoyl-2-arachidonoyl-GPI (18:0/20:4) 0,00051977
GCST90199652 1-stearoyl-2-oleoyl-GPS (18:0/18:1) 0,02555615
GCST90199664 Phenyllactate (PLA) 0,01272859
GCST90199681 2-hydroxyoctanoate 0,00388752
GCST90199704 3-hydroxysebacate 0,02108698
GCST90199749 Gamma-glutamylthreonine 0,01482424
GCST90199770 1-arachidonylglycerol (20:4) 0,00037937
GCST90199790 2-palmitoleoyl-GPC (16:1) 0,00713541
GCST90199794 1-oleoyl-GPE (18:1) 0,0064445
GCST90199816 3,4-dihydroxybutyrate 0,0457161
GCST90199828 N-acetylserine 0,03545266
GCST90199861 Pregnenediol sulfate (C21H34O5S) 0,00620384
GCST90199875 13-HODE + 9-HODE 0,02436659
GCST90199879 Ergothioneine 0,0122909
GCST90199883 Cysteinylglycine disulfide 0,04409296
GCST90199899 1-(1-enyl-palmitoyl)-GPC (p-16:0) 0,04371435
GCST90199901 1-methyl-5-imidazoleacetate 0,02084982
GCST90199910 1-(1-enyl-stearoyl)-GPE (p-18:0) 0,03700612
GCST90199936 3-methyl catechol sulfate (2) 0,00225296
GCST90199952 2-aminoheptanoate 0,0471971
GCST90199986 Eugenol sulfate 0,02831923
GCST90200028 1-stearoyl-2-oleoyl-gpc (18:0/18:1) 0,03353492
GCST90200030 1,2-dilinoleoyl-GPC (18:2/18:2) 0,04356157
GCST90200037 1-stearoyl-2-linoleoyl-gpc (18:0/18:2) 0,02938405
GCST90200041 1-palmitoyl-2-stearoyl-gpc (16:0/18:0) 0,04687286
GCST90200046 1-stearoyl-2-docosahexaenoyl-gpc (18:0/22:6) 0,00835308
GCST90200051 1-palmitoyl-2-dihomo-linolenoyl-GPC (16:0/20:3n3 or 6) 0,04290723
GCST90200102 1-palmitoleoyl-2-linolenoyl-GPC (16:1/18:3) 0,01098387
GCST90200104 Hexadecadienoate (16:2n6) 0,02519585
GCST90200161 2-hydroxyarachidate 0,02755643
GCST90200222 Dihydrocaffeate sulfate (2) 0,00510208
GCST90200234 Picolinoylglycine 0,0205488
GCST90200243 Hydroxypalmitoyl sphingomyelin (d18:1/16:0(OH)) 0,04697794
GCST90200316 N-acetylglucosaminylasparagine 0,03549567
GCST90200319 Cys-gly, oxidized 0,00216651
GCST90200320 Dihomo-linoleate (20:2n6) 0,00119897
GCST90200364 Cysteinylglycine 0,01360229
GCST90200379 Hypotaurine 0,03014081
GCST90200394 Inosine 0,00761015
GCST90200447 Maltose 0,04370196
GCST90200452 Plasma free asparagine 0,03560774
GCST90200462 X-11299 0,01505161
GCST90200474 X-11444 0,04987119
GCST90200488 X-12117 0,02906436
GCST90200524 X-13695 0,00992943
GCST90200526 X-14056 0,00904827
GCST90200547 X-17654 0,03591522
GCST90200596 X-23655 0,01764105
GCST90200601 X-23654 0,01063422
GCST90200614 X-23780 0,00499579
GCST90200672 X-26054 0,03080663
GCST90200696 N6,N6-dimethyllysine 0,03796103
GCST90200708 X-12112 0,00021692
GCST90200710 X-13431 0,02265676
GCST90200711 X-19141 0,03481623
GCST90200717 3-phosphoglycerate / adenosine 5′-diphosphate (ADP) 0,01479885
GCST90200731 Adenosine 5′-diphosphate (ADP) / mannose 0,03623322
GCST90200733 Adenosine 5′-diphosphate (ADP) / N-acetylglucosamine / N-acetylgalactosamine 0,03158844
GCST90200739 Adenosine 5′-monophosphate (AMP) / proline 0,0480536
GCST90200749 Arachidonate (20:4n6) / pyruvate 0,03241957
GCST90200795 Oleoyl-linoleoyl-glycerol (18:1 to 18:2) [2] / linoleoyl-arachidonoyl-glycerol (18:2 to 20:4) [2] 0,0450439
GCST90200876 Cortisone / 4-cholesten-3-one 0,01656538
GCST90200884 Mannose / N-acetylglucosamine / N-acetylgalactosamine ratio 0,00172666
GCST90200886 Phenylpyruvate / 4-hydroxyphenylpyruvate 0,04604498
GCST90200895 Hypotaurine / cysteine 0,00096089
GCST90200904 Phosphate / linoleoyl-arachidonoyl-glycerol (18:2 to 20:4) [1] 0,01887088
GCST90200908 Retinol (Vitamin A) / linoleoyl-arachidonoyl-glycerol (18:2 to 20:4) [2] 0,04377634
GCST90200913 Glucose / sucrose 0,03063799
GCST90200919 Caffeine / theophylline 0,023528
GCST90200934 Acetylcarnitine (C2) / propionylcarnitine (C3) 0,02407541
GCST90200952 Adenosine 5′-diphosphate (ADP) / cytidine 0,03408387
GCST90200956 Cytidine / N-acetylglucosamine / N-acetylgalactosamine ratio 0,031094
GCST90200963 Inosine 5′-monophosphate (IMP) / urate 0,04239604
GCST90200971 Leucine / phosphate 0,00364409
GCST90200979 Arachidonate (20:4n6) / linoleate (18:2n6) 0,0003571
GCST90200981 Caffeine / linoleate (18:2n6) 0,04354453
GCST90200983 Cholesterol / linoleoyl-arachidonoyl-glycerol (18:2 to 20:4) [1] 0,01367908
GCST90200992 Alanine / asparagine 0,02078138

Plasma metabolites increase and decrease skin cancer risk

Metabolites method nsnp pval or or_lci95 or_uci95
Caffeine / linoleate (18:2n6) Inverse variance weighted 13 0,043545 1,076646 1,002141 1,15669
Arachidonate (20:4n6) / pyruvate Inverse variance weighted 14 0,03242 1,065368 1,005318 1,129004
X-13695 Inverse variance weighted 16 0,009929 1,075629 1,017637 1,136926
Hexadecadienoate (16:2n6) Inverse variance weighted 17 0,025196 1,097468 1,011634 1,190584
Cysteinylglycine disulfide Inverse variance weighted 18 0,044093 1,060359 1,00155 1,122622
X-14056 Inverse variance weighted 18 0,009048 1,063733 1,01551 1,114245
Adenosine 5′-diphosphate (ADP) / cytidine Inverse variance weighted 18 0,034084 1,061076 1,00446 1,120882
1-stearoyl-2-oleoyl-GPS (18:0/18:1) levels Inverse variance weighted 19 0,025556 1,080005 1,009451 1,15549
Cysteinylglycine Inverse variance weighted 19 0,013602 1,09644 1,019119 1,179626
13-HODE + 9-HODE Inverse variance weighted 20 0,024367 1,082627 1,010325 1,160103
Maltose Inverse variance weighted 20 0,043702 1,062032 1,0017 1,125997
X-11299 Inverse variance weighted 20 0,015052 1,073446 1,01383 1,136568
Adenosine 5′-monophosphate (AMP) / proline Inverse variance weighted 20 0,048054 1,069258 1,000572 1,142658
2-hydroxyoctanoate Inverse variance weighted 21 0,003888 1,070316 1,022062 1,120849
3-hydroxysebacate Inverse variance weighted 21 0,021087 1,069122 1,01009 1,131605
1-arachidonylglycerol (20:4) Inverse variance weighted 22 0,000379 1,094837 1,041475 1,150933
1-stearoyl-2-arachidonoyl-GPI (18:0/20:4) Inverse variance weighted 23 0,00052 1,083601 1,035561 1,13387
Leucine / phosphate Inverse variance weighted 23 0,003644 1,102396 1,032277 1,177277
N-acetylserine Inverse variance weighted 24 0,035453 1,079408 1,005215 1,159077
1-(1-enyl-stearoyl)-GPE (p-18:0) Inverse variance weighted 24 0,037006 1,053769 1,003161 1,106929
Cys-gly, oxidized Inverse variance weighted 24 0,002167 1,076121 1,026824 1,127786
N6,N6-dimethyllysine Inverse variance weighted 24 0,037961 1,033057 1,001808 1,06528
Arachidonate (20:4n6) / linoleate (18:2n6) Inverse variance weighted 24 0,000357 1,075175 1,033228 1,118825
2-palmitoleoyl-GPC (16:1) Inverse variance weighted 25 0,007135 1,076291 1,020161 1,135508
1-(1-enyl-palmitoyl)-GPC (p-16:0) Inverse variance weighted 25 0,043714 1,057154 1,001567 1,115827
3-methyl catechol sulfate (2) Inverse variance weighted 25 0,002253 1,068963 1,024187 1,115697
Phenyllactate (PLA) Inverse variance weighted 26 0,012729 1,078143 1,016175 1,143889
1-stearoyl-2-docosahexaenoyl-gpc (18:0/22:6) Inverse variance weighted 27 0,008353 1,064194 1,01611 1,114554
X-11444 Inverse variance weighted 27 0,049871 1,047225 1,000025 1,096652
Phenylpyruvate / 4-hydroxyphenylpyruvate Inverse variance weighted 27 0,046045 1,061408 1,001046 1,125409
1-oleoyl-GPE (18:1) Inverse variance weighted 28 0,006444 1,078553 1,021441 1,138858
Hypotaurine Inverse variance weighted 28 0,030141 1,072348 1,006731 1,142242
X-17654 Inverse variance weighted 28 0,035915 1,042319 1,002728 1,083474
1-palmitoyl-2-stearoyl-gpc (16:0/18:0) Inverse variance weighted 29 0,046873 1,054884 1,000738 1,111959
Dihydrocaffeate sulfate (2) Inverse variance weighted 29 0,005102 1,075662 1,022132 1,131995
X-26054 Inverse variance weighted 30 0,030807 1,038238 1,003474 1,074207
Alanine / asparagine Inverse variance weighted 31 0,020781 1,046554 1,006951 1,087715
X-12117 Inverse variance weighted 32 0,029064 1,043675 1,00437 1,084519
1-stearoyl-2-oleoyl-gpc (18:0/18:1) Inverse variance weighted 33 0,033535 1,068588 1,005182 1,135993
Hypotaurine / cysteine Inverse variance weighted 33 0,000961 1,1238 1,048573 1,204424
X-12112 Inverse variance weighted 35 0,000217 1,054967 1,025471 1,085311
X-23654 Inverse variance weighted 38 0,010634 1,058993 1,013429 1,106605

Metabolites with significant heterogeneity (MR Egger or Inverse variance weighted)

Metabolites Method Q Q_df Q_pval
1-stearoyl-2-oleoyl-gpc (18:0/18:1) MR Egger 45.43 31 0.045 *
1-stearoyl-2-oleoyl-gpc (18:0/18:1) Inverse variance weighted 45.62 32 0.056
2-hydroxyarachidate MR Egger 39.57 20 0.006*
2-hydroxyarachidate Inverse variance weighted 47.17 21 0.001*
Hydroxypalmitoyl sphingomyelin (d18:1/16:0(OH)) MR Egger 48.40 29 0.013*
Hydroxypalmitoyl sphingomyelin (d18:1/16:0(OH)) Inverse variance weighted 48.54 30 0.017*
Cysteinylglycine MR Egger 31.72 17 0.016*
Cysteinylglycine Inverse variance weighted 34.74 18 0.01*
Hypotaurine MR Egger 45.67 26 0.01*
Hypotaurine Inverse variance weighted 45.74 27 0.013*
X-13431 MR Egger 39.43 25 0.033*
X-13431 Inverse variance weighted 39.52 26 0.043*
Cortisone / 4-cholesten-3-one MR Egger 39.82 29 0.087
Cortisone / 4-cholesten-3-one Inverse variance weighted 43.83 30 0.049*
Hypotaurine / cysteine MR Egger 54.17 31 0.006*
Hypotaurine / cysteine Inverse variance weighted 55.86 32 0.005*
Retinol (Vitamin A) / linoleoyl-arachidonoyl-glycerol (18:2 to 20:4) [2] MR Egger 42.15 22 0.006*
Retinol (Vitamin A) / linoleoyl-arachidonoyl-glycerol (18:2 to 20:4) [2] Inverse variance weighted 43.13 23 0.006*
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