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Metabolic changes preceding bladder cancer occurrence among Korean men: a nested case-control study from the KCPS-II cohort

 Youngmin Han  ;  Unchong Kim  ;  Keum Ji Jung  ;  Ji-Young Lee  ;  Kwangbae Lee  ;  Sang Yop Shin  ;  Heejin Kimm  ;  Sun Ha Jee 
 CANCER & METABOLISM, Vol.11(1) : 23, 2023-12 
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Bladder cancer ; Gaussian graphical model ; LC/MS metabolomics ; Lysine metabolism ; Predictive biomarker ; Tryptophan-indole metabolism
BackgroundBladder cancer (BLCA) research in Koreans is still lacking, especially in focusing on the prediction of BLCA. The current study aimed to discover metabolic signatures related to BLCA onset and confirm its potential as a biomarker.MethodsWe designed two nested case-control studies using Korean Cancer Prevention Study (KCPS)-II. Only males aged 35-69 were randomly selected and divided into two sets by recruitment organizations [set 1, BLCA (n = 35) vs. control (n = 35); set 2, BLCA (n = 31) vs. control (n = 31)]. Baseline serum samples were analyzed by non-targeted metabolomics profiling, and OPLS-DA and network analysis were performed. Calculated genetic risk score (GRS) for BLCA from all KCPS participants was utilized for interpreting metabolomics data.ResultsCritical metabolic signatures shown in the BLCA group were dysregulation of lysine metabolism and tryptophan-indole metabolism. Furthermore, the prediction model consisting of metabolites (lysine, tryptophan, indole, indoleacrylic acid, and indoleacetaldehyde) reflecting these metabolic signatures showed mighty BLCA predictive power (AUC: 0.959 [0.929-0.989]). The results of metabolic differences between GRS-high and GRS-low groups in BLCA indicated that the pathogenesis of BLCA is associated with a genetic predisposition. Besides, the predictive ability for BLCA on the model using GRS and five significant metabolites was powerful (AUC: 0.990 [0.980-1.000]).ConclusionMetabolic signatures shown in the present research may be closely associated with BLCA pathogenesis. Metabolites involved in these could be predictive biomarkers for BLCA. It could be utilized for early diagnosis, prognostic diagnosis, and therapeutic targets for BLCA.
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4. Graduate School of Public Health (보건대학원) > Graduate School of Public Health (보건대학원) > 1. Journal Papers
Yonsei Authors
Kimm, Heejin(김희진) ORCID logo https://orcid.org/0000-0003-4526-0570
Lee, Ji Young(이지영) ORCID logo https://orcid.org/0000-0002-7784-1401
Jung, Keum Ji(정금지) ORCID logo https://orcid.org/0000-0003-4993-0666
Jee, Sun Ha(지선하) ORCID logo https://orcid.org/0000-0001-9519-3068
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