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Research Articles|
October 31 2017
A Novel 18-Marker Panel Predicting Clinical Outcome in Breast Cancer
Cancer Epidemiol Biomarkers Prev (2017) 26 (11): 1619–1628.
Validation cohorts
External validation was performed using two different publicly available breast cancer datasets profiled with the Affymetrix Human Genome U133 Set. The GSE1456 dataset consisted of 159 breast tumors, of which 128 had complete information for molecular subtype and histologic grade (18). Survival data were available for DSS, OS, and recurrence-free survival (RFS; time from surgical lesion removal to detection of tumor recurrence). The second dataset (GSE4922) comprised 249 tumors (Uppsala cohort), of which 237 tumors had complete information for age, ER status, tumor size, axillary lymph node status, and histologic grade (19). For this dataset, survival data were available for disease-free survival (DFS), which was defined as time from initial diagnosis to first relapse or breast cancer–related death. Of the 18 identified prognostic genes, 11 genes (ACAA1, ADGRG6, BORCS6, CCNA2, CDKN2A, HJURP, HSPA14, KIAA0494, NEIL3, STAM, and TRIP13) were found on the U133A Affymetrix chip and seven genes (CDCA5, FAM91A1, LRRCC1, MTURN, PRR11, SKA2, and SNX8) were found on U133B Affymetrix chip. To validate all 18 markers, the U133A and U133B sets were first normalized separately, and then, the log2-transformed values for both sets were merged for each cohort.
The third dataset [The Cancer Genome Atlas (TCGA) Breast Invasive Carcinoma dataset; ref. 20] consisted of mRNA sequencing (mRNA-seq) data for 900 primary breast tumors, of which 720 tumors had clinical information for the number of positive axillary lymph nodes, tumor size, age, ER, and PR status. Survival time was given as OS. The clinical characteristics of the validation cohorts stratified by the linear predictor can be found in Supplementary Table S1.
Geenien nimet:
ACAA1, https://www.genecards.org/cgi-bin/carddisp.pl?gene=ACAA1&keywords=ACAA1. Acetyl-CoA acyltransferase1.
ADGRG6, https://www.genecards.org/cgi-bin/carddisp.pl gene=ADGRG6&keywords=ADGRG6. Adhesion G protein- coupled receptor G6.
BORCS6, https://www.genecards.org/cgi-bin/carddisp.pl?gene=BORCS6&keywords=BORCS6 BLOC1-related complex subunit 6.
CCNA2, https://www.genecards.org/cgi-bin/carddisp.pl?gene=CCNA2&keywords=CCNA2. Cyclin-A2.
CDKN2A, https://www.genecards.org/cgi-bin/carddisp.pl?gene=CDKN2A&keywords=CDKN2A . Cyclin dependent kinase inhibitor 2A.
Holliday junction recognition protein. Enables histone binding activity and identical protein binding activity.
Involved in several processes, including CENP-A containing chromatin
assembly; regulation of DNA binding activity; and regulation of
protein-containing complex assembly. Located in kinetochore;
mitochondrion; and nuclear lumen.
HSPA14 . https://www.genecards.org/cgi-bin/carddisp.pl?gene=HSPA14&keywords=HSPA14 . Heat shock protein family A (HSP-70) member 14. Predicted to enable several functions, including ATP binding activity;
misfolded protein binding activity; and unfolded protein binding
activity. Predicted to be involved in several processes, including
cellular response to unfolded protein; chaperone cofactor-dependent
protein refolding; and protein refolding. Located in cytosol.
Colocalizes with ribosome.
EFCAB14 Alias KIAA0494 .
https://www.genecards.org/cgi-bin/carddisp.pl?gene=EFCAB14&keywords=KIAA0494 EF-Hand Calcium Binding Domain 14. Predicted to enable calcium ion binding activity. Predicted to be integral component of membrane.
NEIL3 , (ZGRF3, Zinc finger GRF-type 3), DNA glycosylase/AP lyase Neil3, Endonuclease VIII-like 3. https://www.genecards.org/cgi-bin/carddisp.pl?gene=NEIL3&keywords=NEIL3
NEIL3 belongs to a class of DNA glycosylases homologous to the bacterial
Fpg/Nei family. These glycosylases initiate the first step in base
excision repair by cleaving bases damaged by reactive oxygen species and
introducing a DNA strand break via the associated lyase reaction
(Bandaru et al., 2002 [PubMed 12509226]).[supplied by OMIM, Mar 2008]
Signal Transducing Adaptor Molecule (SH3 Domain And ITAM Motif) 1. Involved in intracellular signal transduction mediated by cytokines and
growth factors. Upon IL-2 and GM-CSL stimulation, it plays a role in
signaling leading to DNA synthesis and MYC induction. May also play a
role in T-cell development. Involved in down-regulation of receptor
tyrosine kinase via multivesicular body (MVBs) when complexed with HGS
(ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as
sorting machinery that recognizes ubiquitinated receptors and transfers
them to further sequential lysosomal sorting/trafficking processes.
(
STAM1_HUMAN,Q92783 )
(Microbial infection) Plays an important role in Dengue virus entry.
Thyroid Hormone Receptor Interactor 13. Human Papillomavirus Type 16 E1 Protein-Binding Protein.
Cell Division Cycle-Associated Protein 5 . Sororin. Predicted to enable chromatin binding activity. Involved in
double-strand break repair; mitotic sister chromatid segregation; and
regulation of cell cycle process. Located in nucleoplasm.Regulator of sister chromatid cohesion in mitosis stabilizing cohesin
complex association with chromatin. May antagonize the action of WAPL
which stimulates cohesin dissociation from chromatin. Cohesion ensures
that chromosome partitioning is accurate in both meiotic and mitotic
cells and plays an important role in DNA repair. Required for efficient
DNA double-stranded break repair.
Family With Sequence Similarity 91 Member A1. Involved in intracellular protein transport and vesicle tethering to
Golgi. Located in cytoplasmic vesicle and trans-Golgi network.As component of the WDR11 complex acts together with TBC1D23 to
facilitate the golgin-mediated capture of vesicles generated using AP-1.
Diseases associated with FAM91A1 include Gastric Cardia Carcinoma and Pontocerebellar Hypoplasia.
Among its related pathways are Signaling by Rho GTPases and RHOH GTPase cycle.
Leucine Rich Repeat And Coiled-Coil Centrosomal Protein 1. This gene encodes a centrosomal protein that maintains the structural
integrity of the centrosome and plays a key role in mitotic spindle
formation. The encoded protein contains an N-terminal leucine-rich
repeat domain and a C-terminal coiled-coil domain. It associates with
the centrosome throughout the cell cycle and accumulates on the mitotic
centrosome. Required for the organization of the mitotic spindle. Maintains the structural integrity of centrosomes during mitosis.
Maturin Neural Progenitor Differentiation Regulator Protein,Involved in negative regulation of NF-kappaB transcription factor
activity; positive regulation of MAPK cascade; and positive regulation
of megakaryocyte differentiation. Located in cytoplasm..
Diseases associated with MTURN include Polycystic Kidney Disease 2 With Or Without Polycystic Liver Disease.
Promotes megakaryocyte differentiation by enhancing ERK and JNK
signaling as well as up-regulating RUNX1 and FLI1 expression (PubMed:24681962). Represses NF-kappa-B transcriptional activity by inhibiting phosphorylation of RELA at 'Ser-536' (PubMed:24681962). May be involved in early neuronal development (By similarity).
Proline-Rich Protein 11. Transcription Repressor Of MHCII. Involved in regulation of cell cycle. Located in cytoplasm and nucleus. Broad expression in bone marrow (RPKM 3.3), lymph node (RPKM 2.7) and 20 other tissues PRR11 (Proline Rich 11) is a Protein Coding gene.
Diseases associated with PRR11 include Klatskin's Tumor.
Ubiquitinated (Probable).
Rapidly degraded by the proteasome; degradation may involve FBXW7-specific phosphorylated phosphodegron motifs.https://pubmed.ncbi.nlm.nih.gov/36727626/
Rapidly degraded by the proteasome; degradation may involve FBXW7-specific phosphorylated phosphodegron motifs.https://pubmed.ncbi.nlm.nih.gov/36727626/
Spindle And Kinetochore Associated Complex Subunit 2 .Component of the SKA1 complex, a microtubule-binding subcomplex of the
outer kinetochore that is essential for proper chromosome segregation
(PubMed:17093495, 19289083, 23085020).
Required for timely anaphase onset during mitosis, when chromosomes
undergo bipolar attachment on spindle microtubules leading to silencing
of the spindle checkpoint (PubMed:17093495).
The SKA1 complex is a direct component of the kinetochore-microtubule
interface and directly associates with microtubules as oligomeric
assemblies (PubMed:19289083).
The complex facilitates the processive movement of microspheres along a
microtubule in a depolymerization-coupled manner (PubMed:17093495, 19289083). In the complex, it is required for SKA1 localization (PubMed:19289083).
Affinity for microtubules is synergistically enhanced in the presence
of the ndc-80 complex and may allow the ndc-80 complex to track
depolymerizing microtubules (PubMed:23085020).
(
SKA2_HUMAN,Q8WVK7 )
SNX 8, Sortin Nexin 8. https://www.genecards.org/cgi-bin/carddisp.pl?gene=SNX8&keywords=SNX8
Enables identical protein binding activity and phosphatidylinositol
binding activity. Involved in early endosome to Golgi transport and
intracellular protein transport. Located in early endosome membrane.
Colocalizes with retromer complex. [provided by Alliance of Genome
Resources, Apr 2022]
SNX8 (Sorting Nexin 8) is a Protein Coding gene.
Diseases associated with SNX8 include Atrial Tachyarrhythmia With Short Pr Interval and Tetralogy Of Fallot.
Gene Ontology (GO) annotations related to this gene include identical protein binding and phosphatidylinositol binding.
An important paralog of this gene is SNX30. May be involved in several stages of intracellular trafficking. May play
a role in intracellular protein transport from early endosomes to the
trans-Golgi network
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