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Results for “Association and function analysis”

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PubMed1993

Analysis of peripheral blood lymphocyte cell surface density of functional and activation associated markers in young and old hemodialysis patients.

Aging has been associated with specific shifts in various peripheral blood immune competent cell subsets. As part of pre-transplant immune profile evaluation possible parallel age-related changes in mean T-cell surface density of several cluster differentiation and activation linked antigens were into 2 groups: group 1-114 patients 40 years old or younger and group 2-36 patients 55 years old or older. Peripheral blood CD3+, DR+, CD3+DR+, CD4+, CD4+DR+, CD8+, CD8+DR+, CD56+, CD8+CD56+, CD3+IL-2-R+ and CD3+TR+ (interleukin-2 and transferrin receptors bearing CD3+ cells respectively), all mononuclear cells expressing IL-2-R and TR, and CD4+CD45+ cell subsets were analyzed and enumerated by 2-color flow cytometry. Subset relative levels as well as absolute counts were recorded. Cell surface density computation was performed using a computerized mathematical model based on fluorescence intensity vector analysis and cell size score determination based on light scatter pattern from raw data obtained by flow cytometry studies. Younger age was significantly associated with higher absolute cell count of CD3+ (p < 0.001), DR+ (p < 0.05), CD4+ (p < 0.01), CD8+ (p < 0.005), CD3+IL-2-R+ (p < 0.05), CD3+TR+ (p < 0.03) and IL-2-R+ (p < 0.05). Older patients had a slightly higher mean absolute count of CD4+CD45+ subset (p not significant) and significantly higher mean count for CD8+CD56+ cell subset (p < 0.001). When cell subset levels were compared between the 2 groups as the relative fraction of cells expressing a given marker out of all mononuclear cells gated out by flow cytometry, younger age was significantly associated with higher levels of CD3+ (p < 0.005), CD8+ (p < 0.001), CD4+DR+ (p < 0.004), CD3-TR+ (p < 0.05) and CD8+IL-2-R+ (p < 0.05). In contrast, slightly higher subset levels of CD56+ (p not significant), and significantly elevated levels of CD8+CD56+ (p < 0.0019) and CD4+CD45+ (p < 0.004) were observed in the older patients. Cell surface density analysis showed that younger patients had higher mean density per cell of CD3 (p < 0.05), CD8 (p < 0.001), IL-2-R on CD3+ cells (p < 0.05) and TR on CD3+ cells (p < 0.05). Mean cell surface density of CD56 on all CD56+ cells as well as on CD8+ cells was higher in older individuals (p < 0.001 and p < 0.003, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1989

Prediction of microbial aetiology at admission to hospital for pneumonia from the presenting clinical features. British Thoracic Society Pneumonia Research Subcommittee.

The selection of initial antimicrobial treatment in a patient with community acquired pneumonia is an important clinical decision. Because this decision is usually made before the results of specific microbiological tests are available, we attempted to determine how well the presenting clinical features would allow prediction of microbial aetiology in 441 adults admitted to hospital with pneumonia. Five of 90 variable available on admission were selected for inclusion in a multivariate discriminant function analysis because of their strong association with one or more of the major aetiological subsets (Mycoplasma pneumoniae, Streptococcus pneumoniae, "other," and undetermined). These variables were age, number of days ill before admission, presence or absence of bloody sputum and of lobar infiltration on chest radiograph, and white blood cell count. The microbial aetiology was correctly predicted by this discriminant function analysis in only 42% of cases, which gives a quantitative estimate of the degree of difficulty encountered in determining the microbial aetiology at the time of admission for pneumonia. When a similar discriminant function analysis was applied to the third of patients in whom the microbial aetiology was never determined, most of these cases were predicted to be due to Streptococcus pneumoniae.

Adolescent↗

PubMed2004

Refinement of the 6p21.3 quantitative trait locus influencing dyslexia: linkage and association analyses.

Reading disability (RD), or dyslexia, is the most common learning disability with a prevalence rate of ~5%-10% in school-age children. RD is highly heritable with evidence of a neurobiological origin. Linkage studies have identified several quantitative trait loci (QTLs) for RD. The QTL on chromosome 6p21.3 has been independently replicated by several groups and spans a 16.4-Mb (13.8 cM) interval from D6S109 to D6S291. In this study, we performed sib-pair linkage analyses with Haseman-Elston and DeFries-Fulker methods to define more accurately the QTL interval. Linkage was assessed by using five quantitative phenotypes, including a composite measure of reading performance and four component phenotypes. When probands were selected for severe scores, single- and multi-point analyses showed significant linkage with all five phenotypes, converging over an interval of ~3.24 Mb spanning D6S1597 to D6S1571. Maximal linkage converged at marker D6S1554 across phenotypes. Out of 12 genes in the linkage interval, ten clustered within ~680 kb and were selected for association analysis based on central nervous system expression and putative function. Marker-trait associations were assessed by using QTDT (a general test of association for quantitative traits) and the family-based association test (FBAT), and haplotype analysis was performed by using FBAT and the GeneHunter Transmission/Disequilibrium Test TDT. Marker associations were detected in five of the ten genes, results that were corroborated by our haplotype TDT analysis. The results of the association study have thereby allowed us to significantly reduce the number of possible candidate genes and to prioritize genes for further mutation screening.

Adolescent↗

PubMed2005

Age-related changes in cognitive domains. A population-based study.

BACKGROUND AND AIMS: The aim of the present study is to describe the effects of aging on various cognitive domains (global cognitive function, executive function, motor speed) in a population sample of elderly men, and to describe how their age-related changes are influenced by education, depression, or prevalent cerebrovascular accidents (CEVD). METHODS: A cross-sectional observational study was conducted in a cohort of 334 men, 65 to 95 years old, living in rural communities, participating in the Italian cohort of two population studies--MATISS (Malattie cardiovascolari ATerosclerotiche Istituto Superiore di Sanità) and FINE (Finland, Italy, Netherlands, Elderly). Global cognitive function was measured by the Mini-Mental State Examination (MMSE), executive function by the Stroop test, motor speed by the Purdue Pegboard test, and depression by the CES-D test. Prevalence of cerebrovascular accidents (CEVD), myocardial infarction, and diabetes were evaluated by a questionnaire and a clinical examination. Blood pressure, and total and HDL cholesterol were measured. Current smoking status was self-reported. RESULTS: An age-associated decline in global cognitive functions, executive functions, and motor speed was observed. The decline is more apparent after the age of 85 for the MMSE, and after 75 for executive functions and motor speed. Logistic regression analysis revealed that age was independently associated with altered global cognitive functions, executive functions, and motor speed, even after adjusting for education, depression or prevalent CEVD. CONCLUSIONS: In a cohort of community-living elderly men aged 65 to 95 years, age-associated changes in mental functions are more evident after the age of 85. These changes are independent of education, depression, or prevalent CEVD.

Aged↗

PubMed1994

Smoking, alcohol, and nonsteroidal anti-inflammatory drugs in outpatients with functional dyspepsia and among dyspepsia subgroups.

OBJECTIVE: Although there is a paucity of data, environmental factors such as smoking, alcohol, and non-steroidal anti-inflammatory drugs (NSAIDs) are believed to be important in the pathogenesis of functional dyspepsia. We aimed to evaluate, in outpatients presenting for endoscopy, the role of environmental factors in functional dyspepsia. METHODS: A consecutive sample of 73 patients with functional dyspepsia completed a validated questionnaire prior to endoscopy. The comparison group consisted of outpatients attending for endoscopy who did not have functional dyspepsia (n = 658). Logistic regression analysis was used to estimate the association between functional dyspepsia and potential risk factors adjusting for age, gender, socioeconomic status, general health, and irritable bowel syndrome. RESULTS: Smoking, alcohol, aspirin, non-aspirin NSAIDs, and acetaminophen were not associated with functional dyspepsia. Patients were significantly less likely to have functional dyspepsia if they were current or past smokers, and there was a trend for patients to be less likely to have functional dyspepsia if they took NSAIDs regularly. When patients with functional dyspepsia were classified into symptom subgroups, the environmental factors were not found to be associated with ulcer-like dyspepsia (vs. nonspecific dyspepsia or organic disease). CONCLUSIONS: Smoking, alcohol, and NSAIDs are not associated with an increased risk of functional dyspepsia in outpatients presenting for endoscopy.

Alcohol Drinking↗

PubMed1981

Respiratory infections and their influence on lung function in children: a multiple regression analysis.

The relationship between a history of respiratory infections (and associated variables) in children and lung function in later life was examined in a study among 228 children aged 7 to 11 years. In a multiple regression analysis only a few variables showed marked and consistent effects on lung function. Respiratory tract infections showed increasing impairment of lung function with repeated infections, but the impairment was smaller than that caused by current asthma.

Asthma↗

PubMed1991

Limb function following conservation treatment of adult soft tissue sarcoma.

Quality of life and limb function were studied in 54 patients who were disease-free 2 or more years after limb-conserving treatment for soft tissue sarcoma of the leg or pelvic girdle. Tumours of the thigh predominated (25 patients) and the mean tumour size was 9.9 cm. 41 patients had been treated with a combination of surgery and radiotherapy (29 with conventional and 12 with high dose), 12 with surgery alone and one with irradiation and intra-arterial doxorubicin. Only 15 patients had a normal range of movement in all lower limb joints and only 12 had normal power in all muscle groups; tumours of the lower leg were particularly unfavourable in this respect. Gait was normal in 42 patients but 8 required a walking aid and 4 a joint support. 16 had detectable lymphoedema but only 2 needed to wear compression hosiery. 35 patients still experienced pain at some time but only 6 required analgesia. However, when assessed by questionnaire for locomotion, grooming and home/leisure/vocational activities, 37 patients (68%) reported excellent function, and only 2 had moderate impairment. Function loss was most marked in leisure (25 patients) and vocational (8) activities, but was mild in 66% of cases. Multivariate analysis was carried out to determine the prognostic factors for poor limb function. The results suggested that overall functional score was predominantly determined by gait (P less than 0.001), muscle power or range of movement (P less than 0.001), with increasing age, female sex and the use of radiotherapy poor prognostic factors. Reduced muscle power or range of movement were the major factors determining gait (P less than 0.02) with the use of radiotherapy the significant prognostic factor for both in the conventionally treated group. Doses in excess of 60 Gy resulted in increased fibrosis and a worse functional outcome. Extent of surgery was not an independent prognostic factor for limb function, although univariate analysis suggested an association with range of movement in the conventionally treated group (P less than 0.025). Despite significant objective loss of range of movement and muscle power patients retain excellent limb function and quality of life following limb conserving treatment. For optimal function, radiotherapy should be given with small fractions to a dose not exceeding 60 Gy.

Adult↗

PubMed2001

A general method for the quantitative analysis of functional chimeras: applications from site-directed mutagenesis and macromolecular association.

Two new parameters, I: and C:, are introduced for the quantitative evaluation of functional chimeras: I: (impact) and C: (context dependence) are the free energy difference and sum, respectively, of the effects on a given property measured in forward and retro chimeras. The forward chimera is made by substitution of a part "a" from ensemble A into the analogous position of homologous ensemble B (S:(B --> A)). The C: value is a measure of the interaction of the interrogated position with its surroundings, whereas I: is an expression of the quantitative importance of the probed position. Both I: and C: vary with the evaluated property, for example, kinetics, binding, thermostability, and so forth. The retro chimera is the reverse substitution of the analogous part "b" from B into A, S:(A --> B). The I: and C: values derived from original data for forward and retro mutations in aspartate and tyrosine aminotransferase, from literature data for quasi domain exchange in oncomodulin and for the interaction of Tat with bovine and human TAR are evaluated. The most salient derived conclusions are, first, that Thr 109 (AATase) or Ser 109 (TATase) is an important discriminator for dicarboxylic acid selectivity by these two enzymes (I: < -2.9 kcal/mol). The T109S mutation in AATase produces a nearly equal and opposite effect to S109T in TATase (C: < 0.4 kcal/mol). Second, an I: value of 5.5 kcal/mol describes the effects of mirror mutations D94S (site 1) and S55D (site 2) in the Ca(2+) binding sites of oncomodulin on Ca(2+) affinity. The second mirror set, G98D (site 1) and D59G (site 2), yields a smaller impact (I: = -3.4 kcal/mol) on Ca(2+) binding; however, the effect is significantly more nearly context independent (C: = -0.6 versus C: = -2.7 kcal/mol). Third, the stem and loop regions of HIV and BIV TAR are predominantly responsible for the species specific interaction with BIV Tat(65-81) (I: = -1.5 to -1.6 kcal/mol), whereas I: = 0.1 kcal/mol for bulge TAR chimeras. The C: values are from -0.3 to -1.2 kcal/mol. The analysis described should have important applications to protein design.

Aspartate Aminotransferases↗

PubMed2025

Beyond parental lines: multi-omics analyses reveal epigenetic and transcriptional mechanisms underlying heterosis in Oryza sativa × Oryza rufipogon hybrids.

Heterosis, or hybrid vigor, refers to the superior phenotypes of a hybrid compared with their parents and is widely exploited in agriculture. Interspecific hybrids within the Oryza genus demonstrate significant potential for the systematic improvement of rice varieties. Nevertheless, the mechanistic basis underlying heterosis in interspecific Oryza hybrids remains poorly understood. Here, we systematically performed phenotypic characterization, whole-genome bisulfite sequencing, RNA sequencing, and small RNA profiling using Oryza sativa L. ssp. japonica cv. Nipponbare (NIP), Oryza rufipogon Griff. acc. CWR, and their resulting F1 hybrid (named as NC). NIP and CWR showed distinct phenotypic and molecular differences. The interspecific hybrid, NC, exhibited significant yield heterosis. In the hybrid, most epigenetic and transcriptional features displayed additive inheritance patterns relative to parental lines. Analysis revealed that domestication-selected genes maintained relatively low DNA methylation coupled with high expression levels in both hybrid and parental lines. Additionally, we identified that non-additive miRNAs were potentially involved in regulating fertility, cell growth, and cell division processes in the hybrid. A significant negative correlation was observed between DNA methylation level and gene expression. Functional enrichment analysis revealed that hybrid-MPV DEGs were significantly associated with flowering time regulation, carbohydrate metabolism, photosynthesis, protein phosphorylation, seed development, and defense responses. Through weighted gene co-expression network analysis, we identified 102 functional gene modules, six of which were significantly associated with yield-related heterosis. Collectively, our results provide a multi-omics framework for understanding interspecific hybridization between elite cultivars and wild rice relatives, highlighting CWR as an untapped genetic reservoir for rice improvement.

Oryza↗

PubMed2003

Serotonin 5-HT(2B) receptor loss of function mutation in a patient with fenfluramine-associated primary pulmonary hypertension.

OBJECTIVE: Appetite-suppressant drug fenfluramine is implicated in primary pulmonary hypertension (PPH) but the molecular pathways that mediate this effect are unknown. A mouse model incriminates the serotonin 5-HT(2B) receptor but contrasts with other models where this receptor has been shown to mediate pulmonary arterial relaxation via nitric oxide production. METHODS: We analyzed the human 5-HT(2B) gene in 10 patients with appetite-suppressant drug-associated PPH. RESULTS: A mutation causing premature truncation of the protein product was found in one patient. The mutation was not found in 80 control subjects and no 5-HT(2B) mutation was found in 18 PPH patients not associated with appetite-suppressants. Functional analysis of the transfected receptor expressed either transiently in COS cells or stably in CHO cells demonstrated that the mutated receptor fails to activate the second messenger inositol-phosphates cascade and subsequent intracellular calcium release, in spite of normal expression at the cell membrane. The mutated receptor had no constitutive activity, and produced no dominant negative effect on the wild-type receptor. CONCLUSION: Loss of serotonin 5-HT(2B) receptor function may predispose to fenfluramine-associated PPH in man.

Animals↗

PubMed2004

Molecular and functional analysis of the dictyostelium centrosome.

The centrosome is a nonmembranous, nucleus-associated organelle that functions not only as the main microtubule-organizing center but also as a cell cycle control unit. How the approximately 100 different proteins that make up a centrosome contribute to centrosome function is still largely unknown. Considerable progress in the understanding of centrosomal functions can be expected from comparative cell biology of morphologically different centrosomal structures fulfilling conserved functions. Dictyostelium is an alternative model organism for centrosome research in addition to yeast and animal cells. With the elucidation of morphological changes and dynamics of centrosome duplication, the establishment of a centrosome isolation protocol, and the identification of many centrosomal components, there is a solid basis for understanding the biogenesis and function of this fascinating organelle. Here we give an overview of the prospective protein inventory of the Dictyostelium centrosome based on database searches. Moreover, we focus on the comparative cell biology of known components of the Dictyostelium centrosome including the gamma-tubulin complex and the homologues of centrin, Nek2, XMAP215, and EB1.

Animals↗

PubMed2002

Activation of microsomal epoxide hydrolase by interaction with cytochromes P450: kinetic analysis of the association and substrate-specific activation of epoxide hydrolase function.

The kinetics of the association between cytochrome P450 (P450) and microsomal epoxide hydrolase (mEH) was studied by means of resonant mirror based on the principle of surface plasmon resonance. The dissociation equilibrium constants (K(D)) for the affinity of P450 enzymes for mEH were estimated by resonant mirror using an optical biosensor cell covalently bound to rat mEH. Comparable K(D) values were obtained for CYP1A1 and 2B1, and these were greater by one order of magnitude than that for the CYP2C11. To clarify the influences of P450 enzymes on the catalytic activity of mEH, the hydrolyzing activity for styrene oxide and benzo(a)pyrene-7,8-oxide [B(a)P-oxide] was analyzed in the presence or absence of P450s. Styrene oxide hydrolysis was activated by all P450s including the CYP1A, 2B, 2C, and 3A subfamilies. In agreement with the association affinity determined by resonant mirror, CYP2C11 tends to have enhanced activity for styrene oxide hydrolysis. On the other hand, B(a)P-oxide hydrolysis was enhanced by only CYP2C11 while CYP1A1 and CYP2B1 had no effect. These results suggest that (1) many P450 enzymes associate nonspecifically with mEH, (2) the CYP2C11 plays a greater role in the association/activation of mEH and (3) the P450-mediated activation of mEH depends upon the substrate of mEH.

Animals↗

PubMed2002

Functional analysis of the Saccharomyces cerevisiae DUP240 multigene family reveals membrane-associated proteins that are not essential for cell viability.

The DUP240 gene family of Saccharomyces cerevisiae is composed of 10 members. They encode proteins of about 240 amino acids which contain two predicted transmembrane domains. Database searches identified only one homologue in the closely related species Saccharomyces bayanus, indicating that the DUP240 genes encode proteins specific to Saccharomyces sensu stricto. The short-flanking homology PCR gene-replacement strategy with a variety of selective markers for replacements, and classical genetic methods, were used to generate strains deleted for all 10 DUP240 genes. All of the knock-out strains were viable and had similar growth kinetics to the wild-type. Two-hybrid screens, hSos1p fusions and GFP fusions were carried out; the results indicated that the Dup240 proteins are membrane associated, and that some of them are concentrated around the plasma membrane.

Amino Acid Sequence↗

PubMed2004

Breakthrough pain characteristics and syndromes in patients with cancer pain. An international survey.

Breakthrough pain (BKP) is a transitory flare of pain that occurs on a background of relatively well controlled baseline pain. Previous surveys have found that BKP is highly prevalent among patients with cancer pain and predicts more severe pain, pain-related distress and functional impairment, and relatively poor quality of life. An international group of investigators assembled by a task force of the International Association for the Study of Pain (IASP) evaluated the prevalence and characteristics of BKP as part of a prospective, cross-sectional survey of cancer pain. Fifty-eight clinicians in 24 countries evaluated a total of 1095 patients with cancer pain using patient-rated items from the Brief Pain Inventory (BPI) and observer-rated measures. The observer-rated information included demographic and tumor-related data, the occurrence of BKP, and responses on checklists of pain syndromes and pathophysiologies. The clinicians reported BKP in 64.8% of patients. Physicians from English-speaking countries were significantly more likely to report BKP than other physicians. BKP was associated with higher pain scores and functional interference on the BPI. Multivariate analysis showed an independent association of BKP with the presence of more than one pain, a vertebral pain syndrome, pain due to plexopathy, and English-speaking country. These data confirm the high prevalence of BKP, its association with more severe pain and functional impairment, and its relationship to specific cancer pain syndromes. Further studies are needed to characterize subtypes of BKP. The uneven distribution of BKP reporting across pain specialists from different countries suggests that more standardized methods for diagnosing BKP are needed.

Analysis of Variance↗

PubMed2002

Mapping quantitative effects of oligogenes by allelic association.

Regression analysis of a quantitative trait as a function of a single diallelic polymorphism has been extended to allelic association by composite likelihood under the Malecot model for multiple markers. We applied the method to 10 single nucleotide polymorphisms (SNPs) spanning 27 kb of the angiotensin-I converting enzyme (ACE) gene in British families, localising a causal SNP between G2530A and 4656(CT)3/2 in the 3' region, at a distance of 21.6+/-0.9 kb from the most proximal SNP T-5491C. Neither they nor the I/D polymorphism is causal. To clarify genetic parameters we applied combined segregation, linkage and association analysis. Stronger evidence for the 3' region was obtained, with significant evidence of a lesser 5' effect as reported in French and Nigerian families. However, rigorous confirmation requires that the causal SNPs be identified. Both Malecot and parametric analysis appear to have high power by comparison with alternative methods for localizing oligogenes and their causal polymorphisms.

Chromosome Mapping↗

PubMed1997

The association of plasma IL-6 levels with functional disability in community-dwelling elderly.

BACKGROUND: IL-6 is a multifunctional cytokine that has been shown to increase with age. METHODS: Plasma IL-6 was measured by ELISA in 1,727 community-dwelling elderly subjects whose blood was drawn during the third in-person survey of the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE). Demographics, functional status (disability), and disease states were determined. Correlations of these factors with IL-6 were analyzed with Spearman's Rho while differences between groups were assessed by Wilcoxon test. RESULTS: IL-6 levels were higher with age (p = .0001) even in this older population (> 70 years). There was a positive correlation between IL-6 and functional disability for each of the functional status measures (p = .0001), as well as a correlation between self-rated health and IL-6. Significantly higher median levels of IL-6 were found in subjects reporting prevalent cancer, heart attack, and high blood pressure, but not diabetes or arthritis. The association between age and functional status with high IL-6 remained when all other variables were controlled, in multivariable analysis. CONCLUSIONS: This association between increased plasma IL-6 levels and functional status suggests that dysregulation of IL-6 may be related to the functional disability seen with aging, and that IL-6 may be useful as a component of an overall marker of health.

Aged↗

PubMed2006

Predicting domain-specific insight of schizophrenia patients from symptomatology, multiple neurocognitive functions, and personality related traits.

This study examines the contribution of various neurocognitive functions, clinical characteristics, and personality traits to the prediction of three insight dimensions. Clinically stable schizophrenia patients (n=107) residing in the community were evaluated using the Positive and Negative Syndrome Scale, the Scale for the Assessment of Unawareness of Mental Disorder, and a comprehensive battery of instruments to measure personality related variables and neurocognitive functioning. Step-wise multivariate regression analysis indicates significant association of variability in insight dimensions with neurocognitive functioning (20-41%), personality related traits (8-18% temperament factors, 4-7% self-constructs, 10-14% coping styles), severity of symptoms (about 7%), illness duration (6%), and education (about 5%). Poor insight was attributed to impairment in visual and movement skills, sustained attention, executive functions, intensity of autistic preoccupations and positive symptoms, as well as increased novelty seeking behavior, task and emotion oriented coping styles, better self-esteem, self-efficacy, and higher education. Better awareness was related to better performance of neurocognitive tasks, reward dependence behavior, avoidant coping style, and longer illness duration. Aside from common indicators for the various insight dimensions, we defined specific indicators for each insight dimension. Thus, insight dimensions in schizophrenia patients residing in the community were attributed to neurocognitive and personality related factors rather than to psychopathological symptoms. The findings enable better understanding of the multifactorial nature of insight and highlight targets for more effective intervention and rehabilitation.

Adaptation, Psychological↗

PubMed2006

Transcriptomic analysis of an in vitro murine model of ovarian carcinoma: functional similarity to the human disease and identification of prospective tumoral markers and targets.

Ovarian cancer is an aggressive disease of poor prognostic when detected at advanced stage. It is widely accepted that the ovarian surface epithelium plays a central role in disease etiology, but little is known about disease progression at the molecular level. To identify genes involved in ovarian tumorigenesis, we carried out a genome-wide transcriptomic analysis of six spontaneously transformed mouse ovarian surface epithelial (MOSE) cell lines, an in vitro model for human ovarian carcinoma. Loess normalization followed by statistical analysis with control of multiple testing resulted in 509 differentially expressed genes using an adjusted P-value < or = 0.05 as cut-off. The top 20 differentially expressed genes included 10 genes (Spp1, Cyp1b1, Btg1, Cfh, Mt1, Mt2, Igfbp5, Gstm1, Gstm2, and Esr1) implicated in various aspects of ovarian carcinomas, and other 3 genes (Gsto1, Lcn7, and Alcam) associated to breast cancer. Upon functional analysis, the majority of alterations affected genes involved in glutathione metabolism and MAPK signaling pathways. Interestingly, over 20% of the aberrantly expressed genes were related to extracellular components, suggestive of potential markers of disease progression. In addition, we identified the genes Pura, Cnn3, Arpc1b, Map4k4, Tgfb1i4, and Crsp2 correlated to in vivo tumorigenic parameters previously reported for these cells. Taken together, our findings support the utility of MOSE cells in studying ovarian cancer biology and as a source of novel diagnostic and therapeutic targets.

Animals↗