“…We found that aldo-keto reductase family 1 member B10 ( AKR1B10 ), NAD(P)H quinone dehydrogenase 1 ( NQO1 ), and aldo-keto reductase family 1 member C3 ( AKR1C3 ) are highly expressed in HLRCC-associated kidney cancer relative to the other cancer types, all of which have been reported to be highly expressed in HLRCC-associated kidney cancer in association with a dysregulated Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor erythroid 2-related factor 2 (NRF2) axis ( Figure 3 A) ( Ooi et al., 2011 ). In addition, we found that carboxypeptidase D ( CPD ), growth Differentiation Factor 15 ( GDF15 ), S100 calcium binding protein A6 ( S100A6 ), secretory leukocyte peptidase inhibitor ( SLP1 ), paired box 2 ( PAX2 ), KCNQ1 opposite strand/antisense transcript 1 ( KCNQ1OT1 ), metastasis associated in lung adenocarcinoma transcript-1 ( MALAT1 ), and insulin like growth factor 2 mRNA binding protein 2 ( IGF2BP2 ) are highly expressed in HLRCC-associated kidney cancer relative to the other cancer types, all of which have been reported to be expressed in highly aggressive cancers with poor prognosis ( Chen et al., 2015 ; Feng et al., 2020 ; Gao et al., 2021 ; Han et al., 2020 ; Miyazaki et al., 2019 ; Munn and Garkavtsev, 2018 ; Shi et al., 2019 ; Wang et al., 2020 ; Ye et al., 2021 ; Yi et al., 2021 ; Zhang et al., 2021a ). Using Gene Set Enrichment Analysis (GSEA), we compared three types of hereditary kidney cancers and found that gene sets related to cell migration and metastasis were enriched in HLRCC-associated kidney cancer, consistent with the fact that this highly aggressive kidney cancer subtype has a propensity to metastasize from a small primary lesion ( Figure 3 B).…”