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Ding et al. J Transl Genet Genom 2021;5:50-61  I  http://dx.doi.org/10.20517/jtgg.2020.01                                   Page 55

               Table 3. Function and pathway annotation of 36 genes in the iPAM classifier
                                  Immune  Cell adhesion
                Gene   Bone-disease                 Cell   Gene function, disease association, and pathway role (abstracted
                name *    related  pathway /cell-matrix   cycle  from the gene card website, https://www.genecards.org/)
                                   related
                                           related
                ANO7                     Yes            Associated with advanced CaP, a target in CaP diagnosis and
                                                        immunotherapy
                ANTXR1           Yes     Yes            TLR Pathway, ECM proteins, actin cytoskeleton and promotes cell spreading
                ASPN   Yes               Yes            Degradation of extracellular matrix (ECM) proteoglycans, associated with
                                                        Osteoarthritis
                ATP5EP2                                 Purine nucleotides de novo biosynthesis
                AZGP1            Yes                    Member of macroglobulin family; antigen binding; validated predictor of
                                                        metastatic CaP
                C7               Yes                    Pathway of the innate immune system; involved in host immunity
                CCDC6                                   Structural constituent of cytoskeleton, associated with thyroid papillary
                                                        carcinoma
                CD24             Yes                    Modulates growth and differentiation signals to granulocytes and B cells
                CDC42EP5                 Yes            Induces actin filament assembly leading to cell shape changes.
                CYBA             Yes                    TNFR1 Pathway and Class I MHC mediated antigen processing and
                                                        presentation
                DDIT4            Yes                    DDIT4/mTOR axis involved in the differentiation of Th17 cells
                DPT                      Yes            Cell-matrix interactions and matrix assembly, mediate adhesion
                FAM13C1                                 GTPase activator activity
                FBXL8            Yes                     Involved in Class I MHC mediated antigen processing and presentation
                GLO1   Yes                              Risk factor for CaP progression and involved in bone formation and
                                                        resorption
                GLYATL1                                 Cytochrome P450 - arranged by substrate type and Conjugation of
                                                        carboxylic acids
                GMNN                                Yes  Cell cycle regulation, increased expression plays role in colon, rectal and
                                                        breast cancer
                GNPTAB  Yes                             Associated with mucolipidosis II and IIIA with low bone mineral density
                                                        (osteoporosis)
                ITGBL1                   Yes            Participates in cell adhesion as and cell-surface, cell-cell and cell-matrix
                                                        interaction.
                KIF21A                   Yes            Involved in microtubule transport, involved in cell polarity, and migration
                KRT15            Yes     Yes            Involved in the structural integrity of epithelial cells; regulating innate
                                                        immunity
                LBH                                     Contributes to Wnt-induced tumorigenesis
                LRRN1                                   Regulates Differentiation of Embryonic Stem Cells
                LTF              Yes                    Anti-inflammatory activity, induce apoptosis and inhibit proliferation in
                                                        cancer cells.
                MTDH   Yes                              Promotes lung metastasis and also has an effect on bone and brain
                                                        metastasis
                MYBPC1                    Yes           Contributes to the stability and maintenance of sarcomeres.
                NCAPD3                              Yes  Chromosome condensation in prometaphase and Cell Cycle, Mitotic
                NR4A1            Yes                    Involved in Class I MHC mediated antigen processing and presentation
                PCA3                                    Sensitive to androgen-receptor activation, a molecular signature of prostate
                                                        cancer
                RNF39                                   Plays a role in an early phase of synaptic plasticity
                SFRP4  Yes                              Modulators of Wnt signaling, associated with Osteomalacia and Pyle
                                                        Disease
                SLC22A3                                 Disposition of small organic cations and drugs and environmental toxins
                SLC37A3                                 Transporter activity and transmembrane transporter activity
                STRBP                                   DNA and RNA binding, plays a role in regulation of cell growth
                TOP2A                               Yes  Associated with aggressive CaP and drug resistance; Essential in mitosis
                                                        and meiosis
                UGDH                     Yes            Components of the ECM involved in cell migration, and cancer growth and
                                                        metastasis
               *ANO7 and MYBPC1 are also in the Decipher classifier [15] ; Top2A is also in the Prolaris classifier [27] ; AZGP1 and SFRP4 are also in the
               Oncotype DX classifier [26] ; IPAM: Improved prediction analysis of microarray.


               The AUC of survival ROC for the iPAM classifier by Gleason scores and age groups is shown in Table 4. The
               highest AUC of 0.87 (95%CI: 0.78-0.94) was observed in young patients (age ≤ 55 years); an intermediate
               AUC of 0.82 (95%CI: 0.76-0.88) was observed for middle-aged patients (age 56-70 years), and the lowest
               AUC of 0.69 (95%CI: 0.55-0.82) was observed in old patients (age > 70 years) [Figure 3B]. For patients with
               Gleason scores of 7-10, the overall AUC was 0.80 (95%CI: 0.74-0.85), with the highest AUC of 0.85 (95%CI:
               0.75-0.93) in the young group and the lowest AUC of 0.67 (95%CI: 0.50-0.80) in the old group. The iPAM
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