Homo sapiens
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PROVIDER: PRJNA116645 | ENA |
REPOSITORIES: ENA
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Project description:Myeloma is a clonal malignancy of plasma cells. Poor prognosis risk is currently identified by clinical and cytogenetic features. However, these indicators do not capture all prognostic information. Gene expression analysis can be used to identify poor prognosis patients and this can be improved by combination with information about DNA level changes. Using SNP-based gene mapping in combination with global gene expression analysis we have identified homozygous deletions in genes and networks that are relevant to myeloma. From these, we have generated an expression-based signature associated with shorter survival in 247 patients and confirmed this signature in data from 2 independent groups totalling 800 patients. We identified 170 genes with homozygous deletions and corresponding loss of expression. Deletion within the “Cell Death” network was over-represented and cases with these deletions have impaired overall survival. We defined a gene expression signature of 97 cell death genes that reflects prognosis confirmed this in two independent data sets. We developed a simple 6-gene expression signature from the 97-gene signature that can be used to identify poor prognosis myeloma in the clinical environment. The signature can form the basis of future trials aimed at improving the outcome of poor prognosis myeloma.
2010-03-22 | GSE15695 | GEO
Project description:Multiple myeloma immunoglobulin lambda translocations portend poor prognosis
| PRJNA499054 | ENA
Project description:Purpose Chromosomal aberrations are a hallmark of multiple myeloma but their global prognostic impact is largely unknown. Methods We performed a genome-wide analysis of malignant plasma cells from 192 newly myeloma patients using high-density, single-nucleotide polymorphism (SNP) arrays to identify genetic lesions associated with prognosis. Results Our analyses revealed deletions and amplifications in 98% of cases. Amplifications in 1q and deletions in 1p, 12p, 14q, 16q, and 22q were the most frequent lesions associated with adverse prognosis while recurrent amplifications of chromosomes 5, 9, 11, 15 and 19 conferred a favorable prognosis. Multivariate analysis retained three independent lesions: amp(1q23.3), amp(5q31.3) and del(12p13.31). When adjusted to the established prognostic variables ie t(4;14), and serum beta2-microglobulin (Sb2M), del(12p13.31) remained the most powerful independent marker (P <.0001; hazard ratio = 3.17) followed by Sb2M (P <.0001; hazard ratio = 2.78) and amp(5q31.3) (P =.0005; hazard ratio = 0.37). Cases with amp(5q31.3) alone and low Sb2M had an excellent prognosis (5-year overall survival = 87%) conversely cases with del(12p13.31) alone or amp(5q31.3) and del(12p13.31) and high Sb2M had a very poor outcome (5-year overall survival = 20%). Moreover, integration of SNP mapping and gene expression identified CD27 as potential critical gene responsible for poor prognosis of del(12p) myeloma patients. Conclusion These findings demonstrate the power and accessibility of molecular karyotyping to identify novel strong independent prognostic markers: amp(5q31.3) and del(12p13.31) and to provide insights into putative pathways deregulated in sub classes of cancer patients. Keywords: Human chromosome copy-number alterations study 192 myeloma patients at diagnosis examined with 500K Set Affymetrix chips
2009-08-19 | E-GEOD-12896 | biostudies-arrayexpress
Project description:Gene-expression profiles of hepatitis C-related, early-stage liver cirrhosis Background & Aims: Liver cirrhosis affects 1%M-bM-^HM-^R2% of population and is the major risk factor of hepatocellular carcinoma (HCC). Hepatitis C cirrhosis-related HCC is the most rapidly increasing cause of cancer death in the US. Non-invasive methods have been developed to identify patients with asymptomatic, early-stage cirrhosis, increasing the burden of HCC surveillance, but biomarkers are needed to identify patients with cirrhosis who are most in need of surveillance. We investigated whether a liver-derived 186-gene signature previously associated with outcomes of patients with HCC is prognostic for patients newly diagnosed with cirrhosis but without HCC. Methods: We performed gene expression profile analysis of formalin-fixed needle biopsies from the livers of 216 patients with hepatitis C-related early-stage (Child-Pugh class A) cirrhosis who were prospectively followed for a median of 10 years at an Italian center. We evaluated whether the 186-gene signature was associated with death, progression of cirrhosis, and development of HCC. Results: Fifty-five (25%), 101 (47%), and 60 (28%) patients were classified as having poor-, intermediate-, and good-prognosis signatures, respectively. In multivariable Cox regression modeling, the poor-prognosis signature was significantly associated with death (P=.004), progression to advanced cirrhosis (P<.001), and development of HCC (P=.009). The 10-year rates of survival were 63%, 74%, and 85% and the annual incidences of HCC were 5.8%, 2.2%, and 1.5% for patients with poor-, intermediate-, and good-prognosis signatures, respectively. Conclusions: A 186-gene signature used to predict outcomes of patients with HCC is also associated with outcomes of patients with hepatitis C-related early-stage cirrhosis. This signature might be used to identify patients with cirrhosis in most need of surveillance and strategies to prevent their development of HCC. 216 liver biopsy specimens
2013-01-22 | E-GEOD-15654 | biostudies-arrayexpress
Project description:High PSMD4 expression levels in plasma cells are linked to poor prognosis in multiple myeloma. Additional file available-E-TABM-1138.additional.zip
2012-03-31 | E-TABM-1138 | biostudies-arrayexpress
Project description:Multiple myeloma is a relatively common B-cell malignancy that is currently incurable. Certain recurrent genetic abnormalities characteristics of different genetic subtypes have been described. Hyperdiploid myeloma characterized by recurrent trisomies is the most common genetic subtypes. However little is know about it's biology. Another common genetic abnormality is chromosome 13 deletion which is also associated with inferior prognosis. This abnormality is already present at the pre-malignant MGUS stage and is clonally selected with disease progression. Although it is biologically and clinically important the molecular consequence of chromosome 13 deletion is unknown. Experiment Overall Design: Hyperdiploid myeloma was identified using FISH. The gene expression profile of hyperdiploid MM is compared to that of non-hyperdiploid myeloma to identify differentially expressed genes. Molecular heterogeneity within H-MM is analyzed using unsupervised techniques. The distinctive subgroups identified are also tested in MGUS/SMM and NH-MM. The clinical relevance of these subtypes of hyperdiploid myeloma is then analyzed by correlating with relevant clinical information. Chromosome 13 deleted and undeleted MM are identified by FISH and their gene expression profile compared to identify molecular signature.
2008-06-15 | E-GEOD-6477 | biostudies-arrayexpress
Project description:PRL-3 is an oncogenic phosphatase, which is expressed at a higher level in malignant plasma cells from multiple myeloma patients than in plasma cells from healthy donors and high expression is associated with a poor prognosis. We overexpressed PRL-3 in a multiple myeloma cell line and our goal was to find signaling pathways regulated by PRL-3 in myeloma cells.
2021-07-01 | E-MTAB-10436 | biostudies-arrayexpress
Project description:Paillary thyroid cancer (PTC) is the most common type of thyroid malignancy. Extrathyroidal invasion (ETİ), lymph node metastasis, and distance organ metastasis is poor prognostic factor in PTC. The metastasis is still a leading cause of papillary thyroid cancer death. The early detection of metastatic signature is crucial for identification of thyroid cancer prognosis and personalized therapeutic strategies. In the present study, we present thyroid cancer metastasis and invasivenes related miRNAs identified by comprehensive miRNA expression profiling of formalin-fixed paraffin embedded (FFPE) thyroid tissues obtained from patients belonging to intrathyroidal, invasive and metastatic thyroid carcinoma groups
2020-03-23 | GSE129879 | GEO
Project description:Paillary thyroid cancer (PTC) is the most common type of thyroid malignancy. Extrathyroidal invasion (ETİ), lymph node metastasis, and distance organ metastasis is poor prognostic factor in PTC. The metastasis is still a leading cause of papillary thyroid cancer death. The early detection of metastatic signature is crucial for identification of thyroid cancer prognosis and personalized therapeutic strategies. In the present study, we present thyroid cancer metastasis and invasivenes related miRNAs identified by comprehensive miRNA expression profiling of formalin-fixed paraffin embedded (FFPE) thyroid tissues obtained from patients belonging to intrathyroidal, invasive and metastatic thyroid carcinoma groups
2020-03-23 | GSE129878 | GEO
Project description:Purpose Chromosomal aberrations are a hallmark of multiple myeloma but their global prognostic impact is largely unknown. Methods We performed a genome-wide analysis of malignant plasma cells from 192 newly myeloma patients using high-density, single-nucleotide polymorphism (SNP) arrays to identify genetic lesions associated with prognosis. Results Our analyses revealed deletions and amplifications in 98% of cases. Amplifications in 1q and deletions in 1p, 12p, 14q, 16q, and 22q were the most frequent lesions associated with adverse prognosis while recurrent amplifications of chromosomes 5, 9, 11, 15 and 19 conferred a favorable prognosis. Multivariate analysis retained three independent lesions: amp(1q23.3), amp(5q31.3) and del(12p13.31). When adjusted to the established prognostic variables ie t(4;14), and serum beta2-microglobulin (Sb2M), del(12p13.31) remained the most powerful independent marker (P <.0001; hazard ratio = 3.17) followed by Sb2M (P <.0001; hazard ratio = 2.78) and amp(5q31.3) (P =.0005; hazard ratio = 0.37). Cases with amp(5q31.3) alone and low Sb2M had an excellent prognosis (5-year overall survival = 87%) conversely cases with del(12p13.31) alone or amp(5q31.3) and del(12p13.31) and high Sb2M had a very poor outcome (5-year overall survival = 20%). Moreover, integration of SNP mapping and gene expression identified CD27 as potential critical gene responsible for poor prognosis of del(12p) myeloma patients. Conclusion These findings demonstrate the power and accessibility of molecular karyotyping to identify novel strong independent prognostic markers: amp(5q31.3) and del(12p13.31) and to provide insights into putative pathways deregulated in sub classes of cancer patients. Keywords: Human chromosome copy-number alterations study
2009-08-20 | GSE12896 | GEO