Expression Biomarkers of Pharmacological Treatment Outcomes in Women with Unipolar and Bipolar Depression

2021 ◽  
Author(s):  
Monika Dmitrzak-Weglarz ◽  
Aleksandra Szczepankiewicz ◽  
Janusz Rybakowski ◽  
Paweł Kapelski ◽  
Karolina Bilska ◽  
...  

Abstract Introduction This study aimed to find the expression biomarkers of pharmacological treatment response in a naturalistic hospital setting. Through gene expression profiling, we were able to find differentially-expressed genes (DEGs) in unipolar (UD) and bipolar (BD) depressed women. Methods We performed gene expression profiling in hospitalized women with unipolar (n=24) and bipolar depression (n=32) who achieved clinical improvement after pharmacological treatment (without any restriction). To identify DEGs in peripheral blood mononuclear cells (PBMCs), we used the SurePrint G3 Microarray and GeneSpring software. Results After pharmacological treatment, UD and BD varied in the number of regulated genes and ontological pathways. Also, the pathways of neurogenesis and synaptic transmission were significantly up-regulated. Our research focused on DEGs with a minimum fold change (FC) of more than 2. For both types of depression, 2 up-regulated genes, OPRM1 and CELF4 (p=0.013), were significantly associated with treatment response (defined as a 50% reduction on the Hamilton Depression Rating Scale [HDRS]). We also uncovered the SHANK3 (p=0.001) gene that is unique for UD and found that the RASGRF1 (p=0.010) gene may be a potential specific biomarker of treatment response for BD. Conclusion Based on transcriptomic profiling, we identified potential expression biomarkers of treatment outcomes for UD and BD. We also proved that the Ras-GEF pathway associated with long-term memory, female stress response, and treatment response modulation in animal studies impacts treatment efficacy in patients with BD. Further studies focused on the outlined genes may help provide predictive markers of treatment outcomes in UD and BD.

2007 ◽  
Vol 70 (15-16) ◽  
pp. 1264-1277 ◽  
Author(s):  
Kyung Taek Rim ◽  
Kun Koo Park ◽  
Yang Ho Kim ◽  
Yong Hwan Lee ◽  
Jeong Hee Han ◽  
...  

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2383-2383
Author(s):  
Alexander Kohlmann ◽  
Elisabeth Haschke-Becher ◽  
Barbara Wimmer ◽  
Ariana Huber-Wechselberger ◽  
Sandrine Meyer-Monard ◽  
...  

Abstract Gene expression profiling has the potential to offer consistent objective diagnostic test results once a standardized protocol is established. We investigated the robustness, precision, and reproducibility of this technology and present data that complements the Microarray Innovations in LEukemia study (MILE study). In four laboratories, located in Germany (D), Austria (A), and Switzerland (CH) (DACH study), replicates of 112 patient samples were analyzed using the AmpliChip Leukemia research test. Patient samples were centrally collected and diagnosed in daily routine at the Munich Leukemia Laboratory and represented 8 distinct classes of acute and chronic leukemias, with non-leukemia as control group. After purification of the mononuclear cells by Ficoll density centrifugation, 4 × 5 million cells were frozen in lysis buffer and stored at −80°C. Equipped with identical instruments, software, and reagents, study operators were trained on the microarray sample preparation protocol using total RNA from commercially available cell lines. Upon receipt of the frozen lysates each of the four laboratories purified the total RNA from the 112 technical quadruplicates. 99.3% (445/448) of the sample preparations were successfully performed. On average, 8.4 μg, 7.2 μg, 7.4 μg, or 7.5 μg of total RNA, respectively, were isolated from the mononuclear cells from the four laboratories. In three samples less than 1.0 μg of total RNA was obtained and thus the preparation failed. Bland-Altman plots of agreement showed that any two centers were unlikely to have more than an 8.3 μg difference in yield of total RNA from the same sample. On average there was between 0.1 μg to 1.2 μg difference in total RNA yield from the same sample. Further processing of the 445 samples resulted in 437 (98.2%) successfully performed in vitro transcription reactions, i.e. obtained cRNA yield of >8.0 μg. On average there was between 0.4 μg to 7.4 μg difference in cRNA yield from the same sample. After hybridization to microarrays on average, 46.1%, 48.6%, 46.5%, and 47.3% of probe sets were detected as present with mean scaling factors of 4.3, 2.9, 3.9, and 3.7, respectively. The mean values and standard deviations of distributions of the coefficient of variation (CV) within each site over all the probe sets of the quantile normalized signals on the chip were 27.2% (StdDev: 12.3%), 27.0% (StdDev: 12.3%), 27.3% (StdDev: 12.3%), 26.9% (StdDev: 12.4%), respectively. Furthermore, in unsupervised hierarchical cluster and principal component analyses replicates from the same patient always clustered closely together, with no indications of association between gene expression profiles due to different operators or laboratories. In conclusion, we demonstrated that microarray analysis can be performed with remarkably high inter-laboratory reproducibility and with comparable quality and high technical precision across laboratories.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 574-574
Author(s):  
M. Y. Iddawela ◽  
Y. Wang ◽  
R. Russell ◽  
G. Cowley ◽  
M. El-Sheemy ◽  
...  

574 Background: FFPE is a valuable and widely available resource for translational research which to date has been under-used due to technical limitations. Improvement in technology has enabled genome-wide analysis of FFPE samples. We have assessed gene expression and copy number changes in the same cohort of breast cancers to identify markers or pathways important in prediction of treatment response. Methods: FFPE tissues from patients treated with neoadjuvant adriamycin/cyclophosphamide followed by taxanes in a clinical study were used. Gene expression profiling was assessed using the cDNA mediated annealing selection and ligation assay using the cancer panel which assess 502 genes (DASL assay, Illumina). Data was analysed using BeadStudio software. Copy number changes were assessed using the Molecular inversion probe assay with the 50K SNP panel (Affymetrix, California) and analysed using Nexus software (Biodiscovery). Results: Gene expression profiling was carried out on 44 samples. 12/44 (27%) patients had a pathological complete response (pCR) following chemotherapy. Significant differential expression of genes between pCR and non-pCR cancers were shown. TNFRSF5, CTSD, BCL3, ARNT, BIRC3, TGFBR1, MLLT6, and EVI2A were over-expressed and COL18A1, FGF12, IGFBP1 and NOTCH4 which were down-regulated in cancers that have a pCR (p ≤ 0.01). Copy number changes were assessed in 33 samples and comparison of copy number changes in pCR vs. non-pCR showed gains in regions 6q22, 21q21, 4p14, 4q21, 4p14, and loss at 11q11 (p ≤ 0.01). Three regions containing microRNA coding sequences, mir130a (11q11) mir142 (17q23) and mir21 (17q23) showed significant loss among pCR tumours (p < 0.05). Conclusions: This feasibility study shows that FFPE can be used for gene expression and copy number analysis which is a useful tool for the discovery of predictive markers for treatment response in neoadjuvant treatment trials. The role of TNFRSF5, microRNA 21/130a/142, and 11q11 loss should be further investigated as predictive markers of response to chemotherapy. [Table: see text]


2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 9594-9594
Author(s):  
J. Cossman ◽  
K. Johnson ◽  
J. Gottlieb ◽  
M. Elashoff

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