Table II.
Genes most over- and underexpressed in uterine leiomyosarcoma.
| Functional classification | Abbreviations | Functions of unfamiliar genes |
|---|---|---|
| Upregulated | ||
| Cell cycle regulation | CDKN2A (cyclin-dependent kinase inhibitor 2A), CDK4 (cyclin-dependent kinase 4), CDKN2A (cyclin-dependent kinase inhibitor 2A, also known as p16), CCND1 (cyclin D1) and CCND3 (cyclin D3), CKS2 (CDC28 protein kinase regulatory subunit 2), FOXM1 (forkhead box M1), FOXM1 (forkhead box M1), PTTG1 (pituitary tumor-transforming 1), PRC-1 (protein regulator of cytokinesis 1), UBE2C (ubiquitin-conjugating enzyme E2C), COPS3 (COP9 constitutive photomorphogenic homolog subunit 3), MDM2 (p53 E3 ubiquitin protein ligase homolog) | CKS2, binding to the catalytic subunit of cyclin-dependent kinases; FOXM1, a transcriptional activator involved in cell proliferation and regulation of the expression of several cell cycle genes, such as cyclins B1 and D1; PTTG1, an anaphase-promoting complex (APC) substrate with transforming activity; PRC-1, associated with mitotic spindles during mitosis; UBE2C, a gene required for the destruction of mitotic cyclins and for cell cycle progression |
| Cell homeostasis | GRIA2 (glutamate receptor, ionotropic, AMPA 2), NPTX2 (neuronal pentraxin II), CRABP2 (cellular retinoic acid binding protein 2), POPDC2 (popeye domain containing 2), ST5 (suppression of tumorigenicity 5), TOP2A [topoisomerase (DNA) IIα 170 kDa] | CRABP2, a cytosol-to-nuclear shuttling protein for retinoic acid; POPDC2, regulation of cell-cell adhesion and cell migration; ST5, a regulator of MAPK1/ERK2 kinase, which may contribute to its ability to reduce the tumorigenic phenotype; TOP2A, a gene involved in processes such as chromosome condensation, chromatid separation and relief of torsional stress that occurs during DNA transcription and replication |
| Cell structure | ACTC1 (actin), DIAPH3 [diaphanous homolog 3 (Drosophila)], DCX (doublecortin), COL5A2 (collagen, type V, α2), COPS3 (COP9 constitutive photomorphogenic homolog subunit 3), THBS2 (thrombospondin 2), PLP1 (proteolipid protein 1) | DIAPH3, involved in actin remodeling and regulation of cell movement and adhesion; COPS3, a gene proposed to target p53 protein for proteasome-mediated degradation |
| Signal transduction | MAP3K8 (mitogen-activated protein kinase 8), PIK3R1 (phosphoinositide-3-kinase, regulatory subunit 1), IL17B (interleukin 17B), TSPAN31 (tetraspanin 31), SPP1 (secreted phosphoprotein 1, also known as Osteopontin) | IL17B, a T cell-derived cytokine that stimulates the release of TNF-α and IL-1β; SPP1, also known as OPN (Osteopontin), an integrin-binding glycophosphoprotein produced by a variety of tissues (the expression of OPN has been associated with poor prognosis in several tumor types) |
| Growth factors | IGF1 (insulin-like growth factor 1), IGFBP5 (insulin-like growth factor binding protein 5), TGFB3 (transforming growth factor β3) | |
| Transcription factors | E2F1 (E2F transcription factor 1), RB1 (retinoblastoma 1), GLI1 (GLI family zinc finger 1) | |
| Proteinases | MMP9 (matrix metallopeptidase 9), CAPN6 (calpain 6) | |
| Downregulated | ||
| Metabolism | ALDH1A1 (aldehyde dehydrogenase 1 family, member A1), ALDH1B1 (aldehyde dehydrogenase 1 family, member B1) | ALDH1A1, associated with retinol metabolism |
| Cell cycle and structure | CDKN1A (cyclin-dependent kinase inhibitor 1A (p21, Cip1), DPT (dermatopontin), KRT19 (keratin 19), CNN1 (calponin 1, basic, smooth muscle) | DPT, an extracellular matrix protein with possible functions in cell-matrix interactions and matrix assembly; KRT19, a gene responsible for the structural integrity of epithelial cells; CNN1, a basic actin-binding protein capable of inhibiting smooth muscle contraction, and a constitutive element of smooth muscle cells. Reduced expression of CNN1 in leiomyosarcoma. CNN1 is suspected to have a biological role as a tumor-suppressor; IRF1, interferon regulatory transcription factor and regulation of apoptosis and tumor-suppression; CDKN1A, regulator of cell cycle progression at G1 |
| Cell homeostasis | TNXB (tenascin XB) | TNXB, a member of the tenascin family of extracellular matrix glycoproteins with anti-adhesive effects |
| Oncogenes | Mutations in KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog), MED12 (mediator complex subunit 12), IRF1 (interferon regulatory factor 1) | KIT, mutations are associated with gastrointestinal stromal tumors, mast cell disease, acute myelogenous leukemia and piebaldism; MED12, a transcriptional regulator that binds with a CDK8 subcomplex and functions as a tumor suppressor gene |
| Signal transduction | MAP3K5 (mitogen-activated protein kinase 5), RNASE4 (ribonuclease, RNase A family, 4) | MAP3K5, an activator of c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) and RNASE4, a regulator of mRNA cleavage |
Unique genes were classified into several functional gene families: cell cycle regulation, cell homeostasis, cell structure, signal transduction, growth factors, transcription factors, proteinases, metabolism and oncogenes.