Molecular characteristics and expression profiles of glycerol-3-phosphate dehydrogenase 1 (GPD1) gene in pig

Motivation: Despite increasing understanding of the molecular characteristics of cancer, chemotherapy success rates remain low for many cancer types. Studies have attempted to identify patient and tumor characteristics that predict sensitivity or resistance to different types of conventional chemotherapies, yet a concise model that predicts chemosensitivity based on gene expression profiles across cancer types remains to be formulated. We attempted to generate pan-cancer models predictive of chemosensitivity and chemoresistance. Such models may increase the likelihood of identifying the type of chemotherapy most likely to be effective for a given patient based on the overall gene expression of their tumor. Results: Gene expression and drug sensitivity data from solid tumor cell lines were used to build predictive models for 11 individual chemotherapy drugs. Models were validated using datasets from solid tumors from patients. For all drug models, accuracy ranged from 0.81 to 0.93 when applied to all relevant cancer types in the testing dataset. When considering how well the models predicted chemosensitivity or chemoresistance within individual cancer types in the testing dataset, accuracy was as high as 0.98. Cell line–derived pan-cancer models were able to statistically significantly predict sensitivity in human tumors in some instances; for example, a pan-cancer model predicting sensitivity in patients with bladder cancer treated with cisplatin was able to significantly segregate sensitive and resistant patients based on recurrence-free survival times ( P = .048) and in patients with pancreatic cancer treated with gemcitabine ( P = .038). These models can predict chemosensitivity and chemoresistance across cancer types with clinically useful levels of accuracy.

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Distinctive gene expression profiles of CD34 cells from patients with myelodysplastic syndrome characterized by specific chromosomal abnormalities

Blood ◽

10.1182/blood-2004-01-0103 ◽

2004 ◽

Vol 104 (13) ◽

pp. 4210-4218 ◽

Cited By ~ 104

Author(s):

Guibin Chen ◽

Weihua Zeng ◽

Akira Miyazato ◽

Eric Billings ◽

Jaroslaw P. Maciejewski ◽

...

Keyword(s):

Gene Expression ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Small Sample ◽

Hematopoietic Progenitor Cell ◽

Molecular Characteristics ◽

Hematopoietic Progenitor ◽

Trisomy 8 ◽

Monosomy 7 ◽

Cd34 Cells

Abstract Aneuploidy, especially monosomy 7 and trisomy 8, is a frequent cytogenetic abnormality in the myelodysplastic syndromes (MDSs). Patients with monosomy 7 and trisomy 8 have distinctly different clinical courses, responses to therapy, and survival probabilities. To determine disease-specific molecular characteristics, we analyzed the gene expression pattern in purified CD34 hematopoietic progenitor cells obtained from MDS patients with monosomy 7 and trisomy 8 using Affymetrix GeneChips. Two methods were employed: standard hybridization and a small-sample RNA amplification protocol for the limited amounts of RNA available from individual cases; results were comparable between these 2 techniques. Microarray data were confirmed by gene amplification and flow cytometry using individual patient samples. Genes related to hematopoietic progenitor cell proliferation and blood cell function were dysregulated in CD34 cells of both monosomy 7 and trisomy 8 MDS. In trisomy 8, up-regulated genes were primarily involved in immune and inflammatory responses, and down-regulated genes have been implicated in apoptosis inhibition. CD34 cells in monosomy 7 showed up-regulation of genes inducing leukemia transformation and tumorigenesis and apoptosis and down-regulation of genes controlling cell growth and differentiation. These results imply distinct molecular mechanisms for monosomy 7 and trisomy 8 MDS and implicate specific pathogenic pathways.

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Molecular characteristics of papillary thyroid carcinomas without BRAF mutation or RET/PTC rearrangement: relationship with clinico-pathological features

Endocrine Related Cancer ◽

10.1677/erc-08-0081 ◽

2009 ◽

Vol 16 (2) ◽

pp. 467-481 ◽

Cited By ~ 15

Author(s):

Stéphanie Durand ◽

Carole Ferraro-Peyret ◽

Mireille Joufre ◽

Annie Chave ◽

Françoise Borson-Chazot ◽

...

Keyword(s):

Gene Expression ◽

Normal Tissue ◽

Expression Profiles ◽

Strong Association ◽

The Other ◽

Marker Genes ◽

Molecular Characteristics ◽

Papillary Thyroid ◽

Thyroid Carcinomas ◽

Gene Alteration

About 60–70% of papillary thyroid carcinomas (PTC) present a BRAFT1799A gene mutation or a rearrangement of RET gene (RET/PTC). In this study, we examined whether PTC without BRAFT1799A mutation and without RET/PTC rearrangement named PTC-ga(−) were distinguishable from PTC-ga(+) (with one or the other gene alteration) on the basis of gene expression characteristics. We analyzed the mutational state of 116 PTC and we compared gene expression profiles of PTC-ga(+) and PTC-ga(−) from data of a 200 gene macroarray and quantitative PCR. Seventy five PTC were PTC-ga(+) and 41 were PTC-ga(−). Unsupervised analyses of macroarray data by hierarchical clustering led to a complete segregation of PTC-ga(+) and PTC-ga(−). In a series of 42 genes previously recognized as PTC ‘marker’ genes, 22 were found to be expressed at a comparable level in PTC-ga(−) and normal tissue. Thyroid-specific genes, TPO, TG, DIO1, and DIO2 were under-expressed in PTC-ga(+) but expressed at a normal level in PTC-ga(−). A few genes including DUOX1 and DUOX2 were selectively dys-regulated in PTC-ga(−). Tumor grade of PTC-ga(−) was lower than that of PTC-ga(+). There was a strong association between the mutational state and histiotype of PTC; 81% of PTC follicular variants were corresponded to PTC-ga(−), whereas 84% of PTC of classical form were PTC-ga(+). In conclusion, we show that PTC without BRAFT1799A mutation or RET/PTC rearrangement, mainly corresponding to follicular variants, maintain a thyroid differentiation expression level close to that of normal tissue and should be of better prognosis than PTC with one or the other gene alteration.

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Transcriptomic and Mutational Analysis Discovering Distinct Molecular Characteristics Among Chinese Thymic Epithelial Tumor Patients

Frontiers in Oncology ◽

10.3389/fonc.2021.647512 ◽

2021 ◽

Vol 11 ◽

Author(s):

Naixin Liang ◽

Lei Liu ◽

Cheng Huang ◽

Hongsheng Liu ◽

Chao Guo ◽

...

Keyword(s):

Mutational Analysis ◽

Developmental Process ◽

Expression Profiles ◽

Molecular Data ◽

The Cancer Genome Atlas ◽

High Expression ◽

Molecular Characteristics ◽

Epithelial Tumor ◽

Thymic Epithelial Tumors ◽

Underlying Mechanisms

IntroductionThymic epithelial tumors (TETs) are malignancies arising from the epithelium of the thymic gland, rare but with relatively favorable prognosis. TETs have different pathological subtypes: thymomas and thymic carcinoma, and they show different clinical characteristics regarding prognosis, pathology, and molecular profiles, etc. Although some studies have investigated the pathogenesis of TETs, more molecular data is still needed to further understand the underlying mechanisms among different TETs subtypes and populations.MethodsIn this study, we performed targeted gene panel sequencing and whole transcriptome sequencing on the tumor tissues from 27 Chinese TET patients, including 24 thymomas (A, AB, and B subtypes) and 3 thymic squamous cell carcinomas. We analyzed the genetic variations and differentially expressed genes among multiple TET subtypes. Moreover, we compared our data with the published The Cancer Genome Atlas (TCGA) TET data on both the genetic and transcriptomic levels.ResultsCompared with the TCGA TET genomic data, we found that NF1 and ATM were the most frequently mutated genes (each with a frequency of 11%, 3/27). These mutations were not mutually exclusive, since one B1 thymoma showed mutations of both genes. The GTF2I mutation was mainly enriched in subtype A and AB thymomas, consistent with the previous reports. RNA-seq results unveiled that the genes related to thymus development (FGF7, FGF10 and CLDN4) were highly expressed in certain TET subtypes, implicating that the developmental process of thymus might be linked to the tumorigenesis of these subtypes. We found high expression of CD274 (PD-L1) in B2 and B3 thymoma samples, and validated its expression using immunohistochemistry (IHC). Based on the expression profiles, we further established a machine learning model to predict the myasthenia gravis status of TET patients and achieved 90% sensitivity and 70.6% specificity in the testing cohort.ConclusionThis study provides the first genomic and transcriptomic analysis of a Chinese TET cohort. The high expression of genes involved in thymus developmental processes suggests the potential association between tumorigenesis of TETs and dysregulation of developmental pathways. The high expression of PD-L1 in B2 and B3 thymomas support the potential application of immunotherapy on certain thymoma subtypes.

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A novel immune subtype classification of ER-positive, PR-negative and HER2-negative breast cancer based on the genomic and transcriptomic landscape

Journal of Translational Medicine ◽

10.1186/s12967-021-03076-x ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Peiling Xie ◽

Rui An ◽

Shibo Yu ◽

Jianjun He ◽

Huimin Zhang

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Clinical Outcomes ◽

Immune Escape ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Molecular Characteristics ◽

Consensus Clustering ◽

Breast Cancers ◽

Her2 Breast Cancer

Abstract Background The diversity and plasticity behind ER+/PR−/HER2− breast cancer have not been widely explored. It is essential to identify heterogeneous microenvironment phenotypes and investigate specific genomic events driving the formation of these phenotypes. Methods Based on the immune-related gene expression profiles of 411 ER+/PR−/HER2− breast cancers in the METABRIC cohort, we used consensus clustering to identify heterogeneous immune subtypes and assessed their reproducibility in an independent meta-cohort including 135 patients collected from GEO database. We further analyzed the differences of cellular and molecular characteristics, and potential immune escape mechanism among immune subtypes. In addition, we constructed a transcriptional trajectory to visualize the distribution of individual patient. Results Our analysis identified and validated five reproducible immune subtypes with distinct cellular and molecular characteristics, potential immune escape mechanisms, genomic drivers, as well as clinical outcomes. An immune-cold subtype, with the least amount of lymphocyte infiltration, had a poorer prognosis. By contrast, an immune-hot subtype, which demonstrated the highest infiltration of CD8+ T cells, DCs and NK cells, and elevated IFN-γ response, had a comparatively favorable prognosis. Other subtypes showed more diverse gene expression and immune infiltration patterns with distinct clinical outcomes. Finally, our analysis revealed a complex immune landscape consisting of both discrete cluster and continuous spectrum. Conclusion Overall, this study revealed five heterogeneous immune subtypes among ER+/PR–/HER2− breast cancer, also provided important implications for clinical translations.

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Ovarian Circular RNAs Associated with High and Low Fertility in Large White Sows during the Follicular and Luteal Phases of the Estrous Cycle

Animals ◽

10.3390/ani10040696 ◽

2020 ◽

Vol 10 (4) ◽

pp. 696

Author(s):

Huiyan Hu ◽

Jianzhong Xi ◽

Bo Zhou ◽

Jing Zhang ◽

Zhiqiang Li ◽

...

Keyword(s):

Estrous Cycle ◽

Expression Profiles ◽

Differentially Expressed ◽

Low Fertility ◽

Circular Rnas ◽

Molecular Characteristics ◽

Corpora Lutea ◽

Fertility Regulation ◽

Large White ◽

Host Genes

In this study, the ovarian tissues of Large White pigs were mined for novel circular RNAs (circRNAs), following which, their molecular characteristics and potential mechanisms for fertility regulation were examined. RNA sequencing was used for transcriptome analysis of ovarian follicles and corpora lutea in Large White sows with high (H) and low (L) fertility during the follicular (F) and luteal (L) phases of the estrous cycle. In total, 21,386 circRNA derived from 4535 host genes were identified. Differentially expressed circRNAs were detected in the LH vs. LL (1079) and in the FH vs. FL (1077) comparisons, and their host genes were enriched in steroid biosynthesis and forkhead box O (FOXO), thyroid hormone, cell cycle, and tumor growth factor (TGF)-beta signaling pathways. Protein–protein interaction networks were constructed on the basis of the host genes that were significantly enriched in pathways related to reproductive processes, with AKT3 and PP2CB serving as the hub genes in the networks of the LH vs. LL and FH vs. FL comparisons, respectively. The microRNA (miRNA) binding sites of the differentially expressed circRNAs were predicted, and 128 (LH vs. LL) and 113 (FH vs. FL) circRNA–miRNA pairs were identified. Finally, circRNA–miRNA negative regulatory networks were established on the basis of the gene expression profiles and bioinformatic analyses. In the current study, differentially expressed circRNAs were observed in ovarian tissues between the H and L fertility groups in both F and L phases of the estrous cycle, which suggested roles in pig fertility regulation. These findings provide new clues for elucidating fertility differences in pigs.

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Osmotic Balance Regulates Cell Fusion during Mating in Saccharomyces cerevisiae

The Journal of Cell Biology ◽

10.1083/jcb.138.5.961 ◽

1997 ◽

Vol 138 (5) ◽

pp. 961-974 ◽

Cited By ~ 102

Author(s):

Jennifer Philips ◽

Ira Herskowitz

Keyword(s):

Cell Wall ◽

Cell Fusion ◽

Cell Contact ◽

Fusion Event ◽

Glycerol Facilitator ◽

Fusion Defect ◽

Osmotic Balance ◽

Glycerol 3 Phosphate Dehydrogenase ◽

Gpd1 Gene ◽

Cell Cell

Successful zygote formation during yeast mating requires cell fusion of the two haploid mating partners. To ensure that cells do not lyse as they remodel their cell wall, the fusion event is both temporally and spatially regulated: the cell wall is degraded only after cell–cell contact and only in the region of cell–cell contact. To understand how cell fusion is regulated, we identified mutants defective in cell fusion based upon their defect in mating to a fus1 fus2 strain (Chenevert, J., N. Valtz, and I. Herskowitz. 1994. Genetics 136:1287–1297). Two of these cell fusion mutants are defective in the FPS1 gene, which codes for a glycerol facilitator (Luyten, K., J. Albertyn, W.F. Skibbe, B.A. Prior, J. Ramos, J.M. Thevelein, and S. Hohmann. 1995. EMBO [Eur. Mol. Biol. Organ.] J. 14:1360–1371). To determine whether inability to maintain osmotic balance accounts for the defect in cell fusion in these mutants, we analyzed the behavior of an fps1Δ mutant with reduced intracellular glycerol levels because of a defect in the glycerol-3-phosphate dehydrogenase (GPD1) gene (Albertyn, J., S. Hohmann, J.M. Thevelein, and B.A. Prior. 1994. Mol. Cell. Biol. 14:4135– 4144): deletion of GPD1 partially suppressed the cell fusion defect of fps1 mutants. In contrast, overexpression of GPD1 exacerbated the defect. The fusion defect could also be partially suppressed by 1 M sorbitol. These observations indicate that the fusion defect of fps1 mutants results from inability to regulate osmotic balance and provide evidence that the osmotic state of the cell can regulate fusion. We have also observed that mutants expressing hyperactive protein kinase C exhibit a cell fusion defect similar to that of fps1 mutants. We propose that Pkc1p regulates cell fusion in response to osmotic disequilibrium. Unlike fps1 mutants, fus1 and fus2 mutants are not influenced by expression of GPD1 or by 1 M sorbitol. Their fusion defect is thus unlikely to result from altered osmotic balance.

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Molecular Classification of Multiple Myeloma: A Distinct Transcriptional Profile Characterizes Patients Expressing CCND1 and Negative for 14q32 Translocations.

Blood ◽

10.1182/blood.v106.11.1548.1548 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1548-1548

Author(s):

Luca Agnelli ◽

Silvio Bicciato ◽

Michela Mattioli ◽

Sonia Fabris ◽

Daniela Intini ◽

...

Keyword(s):

Gene Expression ◽

Multiple Myeloma ◽

Expression Profiles ◽

Gene Expression Pattern ◽

Marker Genes ◽

Molecular Characteristics ◽

Cyclin D ◽

Expression Data ◽

Chromosome 13Q ◽

13Q Deletion

Abstract The deregulation of CCND1, CCND2 and CCND3 genes represents a common event in multiple myeloma (MM), being at least one of them deregulated in almost all MM tumors. A recently proposed TC classification1 grouped MM patients into five classes on the basis of their cyclins D expression profiles and the presence of the main translocations involving the immunoglobulin heavy-chain (IGH) locus at 14q32. The aim of our study was to identify the putative transcriptional fingerprints associated with the deregulation of the different D-type cyclins and the presence of IGH translocations. The cyclin D expression levels obtained by high-density oligonucleotide microarray analysis of purified plasma cells from 50 MM cases were used to stratify the samples into the five TC classes, along with the molecular characteristics. The cyclin D expression data were validated by means of real-time quantitative PCR analysis; fluorescence in-situ hybridization was used to investigate the cyclin D loci arrangements, and to detect the main IGH translocations and the chromosome 13q deletion. A multi-class classification analysis was performed on the gene expression data and used to identify the transcriptional fingerprints of the 5 TC groups. 112 probe sets were selected as characterizing the TC1, TC2, TC4 and TC5 groups, whereas the TC3 samples showed heterogeneous phenotypes and no marker genes. In particular, TC1, TC4 and TC5 groups were characterized by the molecular signatures associated with the primary IGH translocations target genes. The TC2 group, showing significantly extra copies of the CCND1 locus (P=5.9×10−3) and neither IGH translocations nor the chromosome 13q deletion (P=1.7×10−3), was characterized by the overexpression of 30 genes, mainly involved in protein biosynthesis at translational level. Among the most specifically modulated transcripts within the group we identified a novel gene containing a BTB/POZ domain, typical of many zinc finger transcription factors and associated with transcriptional repression activity. A meta-analysis performed on two publicly available MM datasets, containing almost 250 cases, validated the identified gene expression signatures with a global classification rate (indicating the correct prediction of the TC class for the independent set) of 86% and 90%, respectively. Our data contribute to the understanding of the molecular and biological features of distinct MM subtypes; the identification of a distinctive gene expression pattern in TC2 patients may improve risk stratification and indicate novel therapeutic targets.

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Coexistence of Intracellular and Membrane-Bound Progesterone Receptors in Human Testis

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2004-0793 ◽

2005 ◽

Vol 90 (1) ◽

pp. 474-483 ◽

Cited By ~ 38

Author(s):

Chirag Shah ◽

Deepak Modi ◽

Geetanjali Sachdeva ◽

Sushama Gadkar ◽

Chander Puri

Keyword(s):

Expression Profiles ◽

Progesterone Receptors ◽

Spermatogenic Cell ◽

Human Testis ◽

Molecular Characteristics ◽

Northern Blot Hybridization ◽

Spermatogenic Cells ◽

Female Reproduction ◽

Pr Protein ◽

Membrane Bound

Abstract Progesterone and progesterone receptors (PR) play a crucial role in female reproduction, but their roles in male reproductive physiology are largely unknown. Our previous studies demonstrated the presence of a specific membrane-bound PR in mature human spermatozoa that is known to regulate important sperm functions. The present study was undertaken to determine whether there exist PR in human testis and to investigate their molecular characteristics and expression profiles. PR mRNA and protein were detected in the spermatogenic cells, Sertoli cells, and occasionally the Leydig cells. PR protein was localized in nucleus and cytoplasm of spermatogonia, primary and secondary spermatocytes, and round spermatids in a stage-specific manner. Intense PR localization was observed in stages IV and V, whereas it was low at stages I, II, and III of spermatogenesis. RT-PCR studies revealed the presence of transcripts for PR in human testis and spermatogenic cells. In accordance with the reported molecular sizes of the known isoforms of PR, two mRNA transcripts of 3.8 and 2.8 kb for PR in adult human testis and spermatogenic cell RNA were detected by Northern blot hybridization. Western blot analysis of testicular and spermatogenic cell lysates revealed two bands of 120 and 90 kDa, corresponding to the conventional PR. In these tissue lysates, an additional band of approximately 55 kDa was detected that was also observed as a single band in sperm lysates, indicating that this smaller protein may correspond to the membrane-bound PR. The membrane-bound PR protein was demonstrated on the spermatogenic cells when probed with progesterone-bound fluorescein conjugate. The results of the present study demonstrate the existence of both intracellular PR-B and PR-A mRNA and protein in the spermatogenic cells of the human testis. A membrane-bound PR was also localized in these cells. The varying levels of intracellular PR during different stages of spermatogenesis and the presence of the membrane-bound PR imply the significance of progesterone in male reproductive events such as regulation of spermatogenesis.

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Genome-Wide Characterization of the sHsp Gene Family in Salix suchowensis Reveals Its Functions under Different Abiotic Stresses

International Journal of Molecular Sciences ◽

10.3390/ijms19103246 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3246 ◽

Cited By ~ 9

Author(s):

Jianbo Li ◽

Jin Zhang ◽

Huixia Jia ◽

Zhiqiang Yue ◽

Mengzhu Lu ◽

...

Keyword(s):

Gene Family ◽

Stress Responses ◽

Expression Profiles ◽

Expression Patterns ◽

Purifying Selection ◽

Molecular Characteristics ◽

Specific Expression ◽

Cis Acting ◽

Shsp Gene ◽

Duplication Events

Small heat shock proteins (sHsps) function mainly as molecular chaperones that play vital roles in response to diverse stresses, especially high temperature. However, little is known about the molecular characteristics and evolutionary history of the sHsp family in Salix suchowensis, an important bioenergy woody plant. In this study, 35 non-redundant sHsp genes were identified in S. suchowensis, and they were divided into four subfamilies (C, CP, PX, and MT) based on their phylogenetic relationships and predicted subcellular localization. Though the gene structure and conserved motif were relatively conserved, the sequences of the Hsp20 domain were diversified. Eight paralogous pairs were identified in the Ssu-sHsp family, in which five pairs were generated by tandem duplication events. Ka/Ks analysis indicated that Ssu-sHsps had undergone purifying selection. The expression profiles analysis showed Ssu-Hsps tissue-specific expression patterns, and they were induced by at least one abiotic stress. The expression correlation between two paralogous pairs (Ssu-sHsp22.2-CV/23.0-CV and 23.8-MT/25.6-MT) were less than 0.6, indicating that they were divergent during the evolution. Various cis-acting elements related to stress responses, hormone or development, were detected in the promoter of Ssu-sHsps. Furthermore, the co-expression network revealed the potential mechanism of Ssu-sHsps under stress tolerance and development. These results provide a foundation for further functional research on the Ssu-sHsp gene family in S. suchowensis.

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