Table 1.
Top-five differentially expressed genes (DEGs) (Top) and DE miRNAs (Bottom) in osteosarcoma (OS) phenotypes (C-I-P-T).
| Reference phenotype | Gene symbol | log[fold change (FC)] | Shared phenotypes | Gene symbol | Log(FC) | Shared phenotypes |
|---|---|---|---|---|---|---|
| Tumorigenic Vs non-tumorigenic | BGN | 3.492 | I-T | IL1A | −2.221 | P-T |
| MGP | 3.459 | T | EPB41L3 | −2.338 | P-T | |
| DKK1 | 3.034 | T | NPPB | −2.693 | C-I-P-T | |
| LOX | 2.873 | T | KRT17 | −2.752 | C-I-P-T | |
| TM4SF1 | 2.74 | T | QPCT | −3.081 | I-T | |
| Invasive Vs non-invasive | DCN | 4.197 | I-P-T | KRT17 | −2.945 | C-I-P-T |
| COL1A2 | 2.963 | C-I-P | OCIAD2 | −2.98 | I-T | |
| S100A4 | 2.775 | I | IGFBP7 | −3.213 | I | |
| S100A4 | 2.602 | I | COL4A1 | −3.37 | C-I-P | |
| PDGFRA | 2.375 | I | IER3 | −3.959 | C-I-P | |
| Colony forming Vs non-colony forming | COL1A2 | 2.895 | C-I-P | C9orf58 | −2.963 | I-P |
| HAPLN1 | 2.852 | C-P | LAMA5 | −3.015 | C-I-P | |
| ALPL | 2.832 | C | COL4A1 | −3.126 | C-I-P | |
| KYNU | 2.572 | C-I-P | ACTG2 | −3.384 | C-I-P-T | |
| MAFB | 2.431 | C-P | NPPB | −3.389 | C-I-P-T | |
| Proliferation Vs non-proliferation | COL1A2 | 2.804 | C-I-P | KRT17 | −2.606 | C-I-P-T |
| MAFB | 2.544 | C-P | COL4A1 | −2.643 | C-I-P | |
| NDRG1 | 2.316 | P-T | LAMA5 | −2.962 | C-I-P | |
| SNTB1 | 2.009 | P | ACTG2 | −2.982 | C-I-P-T | |
| SPOCK | 1.979 | I-P-T | NPPB | −3.046 | C-I-P-T | |
| Reference phenotype | miRNA symbol | Log(FC) | Shared phenotypes | miRNA symbol | Log(FC) | Shared phenotypes |
| Tumorigenic Vs non-tumorigenic | hsa-miR-199b-5p | 5.6 | P-T | hsa-miR-133b | −2.1 | T |
| hsa-miR-100* | 3.66 | I-T | hsa-miR-449a | −2.15 | C-I-T | |
| hsa-miR-222 | 3.6 | T | hsa-miR-181a-2* | −2.38 | T | |
| hsa-miR-136 | 3.34 | T | hsa-miR-142-3p | −2.73 | T | |
| hsa-miR-337-5p | 3.06 | T | hsa-miR-15a | −3.9 | T | |
| Invasive Vs non-invasive | hsa-miR-193a-3p | 2.94 | I | hsa-miR-598 | −3.2 | I |
| hsa-miR-100* | 2.44 | I-T | hsa-miR-363 | −3.44 | I | |
| hsa-miR-99a | 2.41 | I | hsa-miR-34a | −3.75 | I | |
| hsa-miR-193a-5p | 2.4 | I | hsa-miR-146a | −4.29 | C-I-P | |
| hsa-miR-449a | 2.09 | C-I-T | hsa-miR-135b | −5.7 | I | |
| Colony forming Vs non-colony forming | hsa-miR-449a | 2.97 | C-I-T | hsa-miR-376c | −2.67 | C-I-P |
| hsa-miR-545 | 2.77 | C | hsa-miR-146a | −2.76 | C-I-P | |
| hsa-miR-505* | 2.57 | C | hsa-miR-497 | −2.82 | C | |
| hsa-miR-452 | 2.47 | C-P | hsa-miR-124 | −2.91 | C | |
| hsa-miR-7 | 2.45 | C | hsa-miR-155 | −5.89 | C | |
| Proliferation Vs non-proliferation | hsa-miR-199b-5p | 3.28 | P-T | hsa-miR-146a | −3.49 | C-I-P |
| hsa-miR-452 | 2.67 | C-P | hsa-miR-377 | −3.51 | P | |
| hsa-miR-34c-5p | 2.63 | P | hsa-miR-155 | −3.67 | P | |
| hsa-miR-152 | 2.34 | P | hsa-miR-376a | −3.69 | C-P | |
| hsa-miR-886-3p | 2.25 | P | hsa-miR-376c | −3.94 | P | |
DEG profiles. (a) Tp state: BGN, encoding a member of the small leucine-rich proteoglycan (SLRP) family of proteins, related to bone growth, muscle development and regeneration, and collagen fibril assembly in multiple tissues, and regulating inflammation and innate immunity; MGP, inhibiting bone formation; DKK1, whose overexpression is associated with osteolytic bone lesions; LOX, encoding a member of the lysyl oxidase family of proteins with a role in tumor suppression, and crosslink collagen fibers in extracellular matrix (ECM), revealing a pre-metastatic niche in bones; TM4SF1, whose encoded protein is member of the tetraspanin family playing a role in the regulation of cell development, activation, growth, and motility; IL1A, an interleukin-1 cytokine involved in various immune responses, inflammatory processes, and hematopoiesis; EPB41L3, involved in multiple cancers. (b) Ip state: DCN, encoding a member of SLRP, mediating tumor suppression, autophagy, inflammation, and angiogenesis; COL1A2, encoding the pro-alpha 2 chain of type I collagen found in most connective tissues; S100A4, part of S100 proteins involved in the regulation of cell cycle progression and differentiation, and implicated in metastasis; PDGFRA, encoding a cell surface tyrosine kinase receptor for the platelet-derived growth factor family, with a possible role in tumor progression. (c) Cp state: ALPL, encoding a member of the alkaline phosphatase family of proteins, possibly linked to skeletal defects; LAMA5, part of Laminins, a family of ECM glycoproteins major non-collagenous constituent of basement membranes, and implicated in cell adhesion, differentiation, migration, and metastasis; ACTG2, involved in cell motility and cytoskeleton maintenance. (d) Pp state: NDRG1, member of the N-MYC downregulated gene family involved in stress responses, hormone responses, cell growth, and differentiation, whose encoded protein is necessary for p53-mediated caspase activation and apoptosis. DE miRNA profiles. hsa-miR-146a, which regulates inflammation and other innate immune system processes, is DE across phenotypes and is known to control cytokine signaling and toll-like receptors by binding to IL1 receptor associated kinase 1 (IRAK1); hsa-mir-199b-5p is highly upregulated in Tp and Pp. Also, these two phenotypes share the DE hsa-miR-100 located in chromosome 11, which contains cancer susceptibility loci and is associated with multiple cancers; hsa-miR-449a, which exerts influence post-transcriptionally in various cancers, presents opposite regulation sign, and recent OS studies showed that when down-expressed, it suppresses tumorigenicity (in vivo) and promotes cell apoptosis (in vitro) (23).