Lumican Research Articles

Lack of association between LUM rs3759223 polymorphism and high myopia.

Previous evidence has indicated that the lumican (LUM) gene is a candidate susceptibility gene of high myopia; however, the association between LUM promoter regions rs3759223 polymorphism and high myopia remains controversial and ambiguous. This study performed a meta-analysis to clarify the association between the rs3759223 polymorphism and high myopia risk. Eligible studies were identified by comprehensive search of PubMed, EMBASE, Web of Science, and Chinese Biomedical Literature database. The crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were used to estimate the association between the rs3759223 polymorphism and high myopia susceptibility. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. Finally, six studies including 1238 cases and 1059 healthy controls were included. Meta-analyses showed no association between rs3759223 polymorphism and high myopia susceptibility in all genetic models (CC vs. TT, OR = 1.089; 95% CI, 0.690 to 1.718; CT vs. TT, OR = 0.865; 95% CI, 0.646 to 1.157; CC + CT vs. TT, OR = 1.202; 95% CI, 0.730 to 1.980; CC vs. CT + TT, OR = 0.914; 95% CI, 0.771 to 1.083) and no significance in subgroup analyses according to the definition of high myopia (based on more myopic than -6.00 diopters vs. not based on more myopic than -6.00 diopters). Publication bias was not evident in this study. This meta-analysis has suggested that there is a lack of association of the rs3759223 polymorphism with high myopia risk. However, further large and well-designed studies with the consideration of LUM gene locus interactions and gene-gene and gene-environment interactions are still required to further evaluate high myopia risk.

Meta-analysis of the association between lumican gene polymorphisms and susceptibility to high Myopia.

BackgroundsMany studies have evaluated the association between lumican (LUM) gene polymorphisms and high myopia. However, the results remain controversial. This meta-analysis aims to comprehensively evaluate the relationship between two common LUM polymorphisms (rs3759223 and rs3759222) and the risk of high myopia.MethodsA comprehensive literature search for studies published up until September of 2013 was performed. Data were extracted independently by two investigators, and the weighted Odds Ratios (ORs) and 95% Confidence Intervals (CIs) for the associations were obtained by using a random-effects model.ResultsEight studies (1425cases and 1271 controls) were identified for the analysis of the association between rs3759223 polymorphism and high myopia. The results indicated that rs3759223 polymorphism was associated with high myopia under a recessive model (OR = 1.71, 95%CI 1.04–2.81). Further subgroup analysis indicated that this polymorphism was associated with high myopia among Chinese people in the additive model (OR = 1.17, 95%CI 1.06–1.29) and a recessive model (OR = 1.75, 95%CI 1.00–3.06) with control group coming from hospital based population. Four studies (1024 cases and 1163 controls) were identified for the analysis of the association between rs3759222 polymorphism and high myopia. The results indicated that rs3759222 polymorphism was not associated with high myopia in all genetic models, even the subgroup analysis couldn't provide relative proof to assure the outcome.ConclusionThis meta-analysis suggests that LUM polymorphisms are associated with the risk of high myopia. However, well-designed studies with larger sample sizes and more ethnic groups are required to further validate this association.

Genes encoding proteoglycans are associated with the risk of anterior cruciate ligament ruptures

BackgroundGenetic variants within genes involved in fibrillogenesis have previously been implicated in anterior cruciate ligament (ACL) injury susceptibility. Proteoglycans also have important functions in fibrillogenesis and maintaining the structural integrity...

Small leucine‐rich proteoglycans exhibit unique spatiotemporal expression profiles during cardiac valve development

Small Leucine Rich Proteoglycans (SLRPs) play a role in collagen fiber formation and also function as signaling molecules. Given the importance of collagen synthesis to the cardiovascular extracellular matrix (ECM), we examined the spatiotemporal expression of SLRPs, not previously investigated in the murine heart. Cardiac expression using antibodies specific for biglycan (BGN), decorin (DCN), fibromodulin (FMOD), and lumican (LUM) revealed distinct patterns among the SLRPs in mesenchymal-derived tissues. DCN showed the most intense localization within the developing valve cusps, while LUM was evident primarily in the hinge region of postnatal cardiac valves. BGN, DCN, and FMOD were immunolocalized to regions where cardiac valves anchor into adjacent tissues. Medial (BGN) and adventitial (BGN, DCN, FMOD and LUM) layers of the pulmonary and aortic arteries also showed intense staining of SLRPs but this spatiotemporal expression varied with developmental age. The unique expression patterns of SLRPs suggest they have adapted to specialized roles in the cardiovascular ECM. SLRP expression patterns overlap with areas where TGFβ signaling is critical to the developing heart. Therefore, we speculate that SLRPs may not only be required to facilitate collagen fiber formation but may also regulate TGFβ signaling in the murine heart.

A multilectin affinity approach for comparative glycoprotein profiling of rheumatoid arthritis and spondyloarthropathy

BackgroundArthritis refers to inflammation of joints and includes common disorders such as rheumatoid arthritis (RA) and spondyloarthropathies (SpAs). These diseases differ mainly in terms of their clinical manifestations and the underlying pathogenesis. Glycoproteins in synovial fluid might reflect the disease activity status in the joints affected by arthritis; yet they have not been systematically studied previously. Although markers have been described for assisting in the diagnosis of RA, there are currently no known biomarkers for SpA.Materials and methodsWe sought to determine the relative abundance of glycoproteins in RA and SpA by lectin affinity chromatography coupled to iTRAQ labeling and LC-MS/MS analysis. We also used ELISA to validate the overexpression of VCAM-1, one of the candidate proteins identified in this study, in synovial fluid from RA patients.Results and discussionWe identified proteins that were previously reported to be overexpressed in RA including metalloproteinase inhibitor 1 (TIMP1), myeloperoxidase (MPO) and several S100 proteins. In addition, we discovered several novel candidates that were overexpressed in SpA including Apolipoproteins C-II and C-III and the SUN domain-containing protein 3 (SUN3). Novel molecules found overexpressed in RA included extracellular matrix protein 1 (ECM1) and lumican (LUM). We validated one of the candidate biomarkers, vascular cell adhesion molecule 1 (VCAM1), in 20 RA and SpA samples using ELISA and confirmed its overexpression in RA (p-value <0.01). Our quantitative glycoproteomic approach to study arthritic disorders should open up new avenues for additional proteomics-based discovery studies in rheumatological disorders.

Histological and molecular characterisation of feline humeral condylar osteoarthritis

BackgroundOsteoarthritis (OA) is a clinically important and common disease of older cats. The pathological changes and molecular mechanisms which underpin the disease have yet to be described. In this study we evaluated selected histological and transcriptomic measures in the articular cartilage and subchondral bone (SCB) of the humeral condyle of cats with or without OA.ResultsThe histomorphometric changes in humeral condyle were concentrated in the medial aspect of the condyle. Cats with OA had a reduction in articular chondrocyte density, an increase in the histopathological score of the articular cartilage and a decrease in the SCB porosity of the medial part of the humeral condyle. An increase in LUM gene expression was observed in OA cartilage from the medial part of the humeral condyle.ConclusionsHistopathological changes identified in OA of the feline humeral condyle appear to primarily affect the medial aspect of the joint. Histological changes suggest that SCB is involved in the OA process in cats. Differentiating which changes represent OA rather than the aging process, or the effects of obesity and or bodyweight requires further investigation.

2D-DIGE to identify proteins associated with gestational diabetes in omental adipose tissue

Gestational diabetes mellitus (GDM) is a significant risk factor for the type 2 diabetes epidemic in many populations. Maternal adipose tissue plays a central role in the pathophysiology of GDM. Thus, the aim of this study was to determine the effect of GDM on the proteome of adipose tissue. Omental adipose tissue was obtained at the time of term Caesarean section from women with normal glucose tolerance (NGT) or GDM. 2D-difference gel electrophoresis (DIGE), followed by mass spectrometry, was used to identify protein spots (n = 6 patients per group). Western blotting was used for confirmation of six of the spot differences (n = 6 patients per group). We found 14 proteins that were differentially expressed between NGT and GDM adipose tissue (≥ 1.4-fold, P < 0.05). GDM was associated with an up-regulation of four proteins: collagen alpha-2(VI) chain (CO6A2 (COL6A2)), fibrinogen beta chain (FIBB (FGB)), lumican (LUM) and S100A9. On the other hand, a total of ten proteins were found to be down-regulated in adipose tissue from GDM women. These were alpha-1-antitrypsin (AIAT (SERPINA 1)), annexin A5 (ANXA5), fatty acid-binding protein, adipocyte (FABP4), glutathione S-transferase P (GSTP (GSTP1)), heat-shock protein beta-1 (HSP27 (HSPB1)), lactate dehydrogenase B chain (LDHB), perilipin-1 (PLIN1), peroxiredoxin-6 (PRX6 (PRDX6)), selenium-binding protein 1 (SBP1) and vinculin (VINC (VCL)). In conclusion, proteomic analysis of omental fat reveals differential expression of several proteins in GDM patients and NGT pregnant women. This study revealed differences in expression of proteins that are involved in inflammation, lipid and glucose metabolism and oxidative stress and added further evidence to support the role of visceral adiposity in the pathogenesis of GDM.

Microarray Analysis of Formalin-Fixed Paraffin-Embedded (FFPET) and Frozen (FZT) Uveal Melanoma Detects Clinically Relevant Abnormalities, Including Chromosome 3 Loss of Heterozygosity

Molecular cytogenetic alterations, specifically monosomy 3, are strongly correlated with metastases and death in uveal melanoma (UVM). Although FISH can be used for the identification of monosomy 3, a subset of UVM exhibit only partial loss of chromosome 3 potentially missed with chromosome enumeration probes. Moreover, often limited material available can compromise detection of additional alterations with potential clinical relevance. Microarray analysis is an alternative method for the analysis of such specimens affording whole genome interrogation. In the current study we performed microarray to detect genomic changes in DNA from FFPET and FZT UVM samples (clinical trial NCT00952939). Of the available cases, 23.5% yielded DNA of sufficient quantity and quality to obtain interpretable microarray results, representing 28 patients. All but one case demonstrated significant abnormalities. Gains of 8q, consistent with an apparent i(8)(q10) karyotype, were the most common finding, seen in 21 patients. Monosomy 3 was detected by microarray in 15 cases. A single case showed partial loss of 3 (3q11.2q25.31), the only clinically significant abnormality detected in that case. All cases lacking chromosome 3 abnormalities showed a copy gain of 6p sharing a small 28.18 Mb region of overlap at 6p25.2p21.33. Additional findings included TERT and NEDD9 amplifications, and CDKN2A/B and LUM gene deletions. SNP analysis revealed three cases with unique regions of copy neutral LOH involving 5p15.33q35.3, 15q11.2q21.1 and one case with whole chromosome LOH for chromosomes 3, 4 and 6. The latter was detected in a FZT specimen, while the paired FFPET sample lacked evidence of LOH and showed monosomy 3, trisomy 4 and whole arm gains and losses of 6p and 6q, respectively, suggesting the presence of tumor heterogeneity. Microarray analysis has identified new recurrent abnormalities associated with UVM with potential relevance to UVM biology, diagnosis and prognosis. Conflict of Interest: Roger Schultz is an employee of Perkin Elmer.

Extracellular matrix and posterior capsular opacification

Posterior capsular opacification (PCO) is one of the major complications of modern cataract surgery.Multiple studies had demonstrated that the extracellular matrix (ECM) plays an important role in the generation and development of PCO.A variety of ECM components,including fibronectin (FN),laminin (LN),collagen,lumican,osteoponin (OPN),decorin,hyaluronic acid and vimentin,affect the biological properties of lens epithelial cells (LECs) through different mechanisms,such as regulating cell migration,adhesion and proliferation.This review focuses on the role of ECM in PCO formation in order to explore the pathogenesis of PCO and provide a potential therapeutic approach for the prevention and management of PCO. Key words: Extracellular matrix; Posterior capsular opacification; Lens epithelial cells

Label-free quantitative proteomic analysis of right ventricular remodeling in infant Tetralogy of Fallot patients

Tetralogy of Fallot (TOF) results in chronic progressive right ventricular (RV) pressure overload and shunt hypoxemia. We investigated the global changes in the proteome of RV among infant patients with and without TOF to gain an insight into early RV remodeling. One hundred and thirty-six differentially expressed proteins were identified using label-free LC-ESI-MS/MS analysis. Western blot results revealed that the expression of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2) increased significantly in TOF patients; and levels of lysocardiolipin acyltransferase 1 (LCLAT1), lumican (LUM), and versican (VCAN) decreased significantly. QRT-PCR analysis showed that levels of PFKFB2 mRNA were markedly increased, but those of LCLAT1 and LUM were significantly decreased. VCAN mRNA showed no significant change in response to pathophysiology of TOF. The results of immunohistochemical staining were similar to those of Western blot analysis. Results of the proteomic analysis indicated that the level of glycolysis-related proteins had increased and levels of lipid-metabolism-related proteins had decreased. ECM proteins were found to be more down-regulated in TOF in the present study than in previous reports. Taken together, our findings may provide clues to both the metabolic inflexibility and ECM remodeling during the early RV remodeling, which occur in response to chronic hypoxia and long-term pressure overload in TOF patients.

Absence of an association between lumican promoter variants and high myopia in the Korean population

Purpose: To determine the association of single nucleotide polymorphisms (SNPs) in the promoter region of the lumican (LUM) gene with high myopic Korean patients.Methods: Genomic DNA samples were obtained from 128 unrelated Korean patients with high myopia who had refractive errors ≤ −9.25 and axial lengths ≥ 26.5 mm in both eyes, and 235 control subjects. We investigated two promoter SNPs of the LUM gene.Results: For the rs3759222, the C/C genotype was less prevalent in the high myopia group compared to the control group (46.1% vs. 53.2%); however, there was no statistical significance (p = 0.068, OR = 0.754, 95% CI: 0.491–1.159). The “C” allele frequency in the high myopia group (68.0%) was slightly lower than the control group (72.6%), but this difference was not statistically significant (p = 0.061, OR = 0.810, 95% CI:0.582–1.126). For the rs3759223, the genotype frequencies of T/T, T/C, and C/C were 67.2%, 26.6%, and 6.2%, respectively, in the high myopia group and 64.7%, 30.6%, and 4.7 %, respectively, in the control group. The allele frequency of T was 80.5% in the high myopia group and 80.0% in the control group (p = 0.077, OR = 1.03, 95% CI: 0.703–1.508). There were no significant differences in the distribution of genotype and allele frequencies for the two promoter SNPs tested.Conclusions: The current study did not support an association between the promoter SNPs of the LUM gene with high myopia in the Korean population.

Detection of differentially expressed lumican gene mRNA level in scleral tissue in human eye

To identify differentially expressed lumican in scleral tissue of eyes with primary open-angle glaucoma (POAG) and high myopia (HM). Total RNA was isolated from scleral tissue of cadaveric eyes derived from normal donors, patient's eyes with diagnosed glaucoma and high myopia who accepted trabeculectomy. RNA was amplified, RT-PCR was used to measure the levels of mRNA. The ratio of the electrophoresis strips'gray scale values of the β-actin over the lumican gene was obtained for ANOVA analysis. β-actin/LUM of normal eye was significantly higher than that of POAG and POAG + HM eyes (P < 0.01), but there was no significant difference between POAG and POAG + HM eyes (P > 0.05). Differentially expressed lumican between POAG and control groups identified in this study have not been previously investigated for their role in the pathogenesis of POAG and thus are novel factors for further study of the mechanism of the disease and for their possible use as diagnostic markers.

Postmortem cardiac tissue maintains gene expression profile even after late harvesting

BackgroundGene expression studies can be used to help identify disease-associated genes by comparing the levels of expressed transcripts between cases and controls, and to identify functional genetic variants (expression quantitative loci or eQTLs) by comparing expression levels between individuals with different genotypes. While many of these studies are performed in blood or lymphoblastoid cell lines due to tissue accessibility, the relevance of expression differences in tissues that are not the primary site of disease is unclear. Further, many eQTLs are tissue specific. Thus, there is a clear and compelling need to conduct gene expression studies in tissues that are specifically relevant to the disease of interest. One major technical concern about using autopsy-derived tissue is how representative it is of physiologic conditions, given the effect of postmortem interval on tissue degradation.ResultsIn this study, we monitored the gene expression of 13 tissue samples harvested from a rapid autopsy heart (non-failed heart) and 7 from a cardiac explant (failed heart) through 24 hours of autolysis. The 24 hour autopsy simulation was designed to reflect a typical autopsy scenario where a body may begin cooling to ambient temperature for ~12 hours, before transportation and storage in a refrigerated room in a morgue. In addition, we also simulated a scenario wherein the body was left at room temperature for up to 24 hours before being found. A small fraction (< 2.5%) of genes showed fluctuations in expression over the 24 hr period and largely belong to immune and signal response and energy metabolism-related processes. Global expression analysis suggests that RNA expression is reproducible over 24 hours of autolysis with 95% genes showing < 1.2 fold change. Comparing the rapid autopsy to the failed heart identified 480 differentially expressed genes, including several types of collagens, lumican (LUM), natriuretic peptide A (NPPA) and connective tissue growth factor (CTGF), which allows for the clear separation between failing and non-failing heart based on gene expression profiles.ConclusionsOur results demonstrate that RNA from autopsy-derived tissue, even up to 24 hours of autolysis, can be used to identify biologically relevant expression pattern differences, thus serving as a practical source for gene expression experiments.

Association Analysis of Polymorphisms in Lumican Gene and Systemic Lupus Erythematosus in a Taiwan Chinese Han Population

Lumican (LUM) is predominantly localized in areas of pathological fibrosis. To determine whether polymorphisms in LUM gene are associated with development of systemic lupus erythematosus (SLE), we analyzed 2 single-nucleotide polymorphisms (SNP) of LUM in a Taiwan Chinese Han population. Participants included 168 patients with SLE and 192 age-matched controls in whom examinations had excluded SLE. Genotyping of -628 A/-(rs17018757) and c.1567 T/C polymorphisms in LUM were carried out in each patient and control using the polymerase chain reaction-restriction fragment-length polymorphism method, and validated by Taqman SNP genotyping assay. Data were correlated with the development of SLE and various clinical symptoms by chi-square analysis. Frequencies of C/C genotype and the C allele at c.1567 T/C were significantly higher in patients than controls. Polymorphism at c.1567 C/T was found to be associated with arthritis and photosensitivity in patients with SLE, which are both connective tissue-related symptoms. The c.1567 T/C polymorphism of LUM is related to the development and clinical symptoms of SLE.

Evaluation of Proteoglycan Gene Polymorphisms as Risk Factors in the Genetic Susceptibility to High Myopia

PURPOSE. To investigate the relationship between high myopia and single nucleotide polymorphisms (SNPs) in six proteoglycan genes: aggrecan (ACAN), fibromodulin (FMOD), decorin (DCN), lumican (LUM), keratocan (KERA), and epiphycan (EPYC). These genes were selected for study because they are involved in induced myopia in animals and/or are within the human MYP3 locus identified by linkage analysis of families with high myopia. METHODS. Two groups of Chinese subjects were studied: group 1 (300 cases and 300 controls) and group 2 (356 cases and 354 controls). Cases were high myopes with spherical equivalent (SE) ≤ -8.00 D, and controls had SE between +1.0 and -1.0 D. From these candidate genes, 60 tagging SNPs were selected. First, 12 DNA pools were each constructed from 50 samples of the same phenotype from group 1 subjects and were tested for association with the SNPs. Second, putatively positive SNPs were confirmed by individual genotyping of group 1 subjects. Finally, positive results were replicated in group 2 subjects. RESULTS. Of the 58 SNPs successfully screened by DNA pooling, 8 ACAN SNPs passed the threshold of P ≤ 0.10 (nested ANOVA) and were then genotyped in the individual samples. Haplotypes rs3784757 and rs1516794 showed significant association with high myopia. However, the positive result could not be replicated in the second subject group. CONCLUSIONS. These six proteoglycan genes were not associated with high myopia in these Chinese subjects and hence are unlikely to be important in the genetic predisposition to high myopia.

Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer: a report from the Ovarian Cancer Association Consortium.

Alterations in stromal tissue components can inhibit or promote epithelial tumorigenesis. Decorin (DCN) and lumican (LUM) show reduced stromal expression in serous epithelial ovarian cancer (sEOC). We hypothesized that common variants in these genes associate with risk. Associations with sEOC among Caucasians were estimated with odds ratios (OR) among 397 cases and 920 controls in two U.S.-based studies (discovery set), 436 cases and 1,098 controls in Australia (replication set 1) and a consortium of 15 studies comprising 1,668 cases and 4,249 controls (replication set 2). The discovery set and replication set 1 (833 cases and 2,013 controls) showed statistically homogeneous (Pheterogeneity≥0.48) decreased risks of sEOC at four variants: DCN rs3138165, rs13312816 and rs516115, and LUM rs17018765 (OR = 0.6 to 0.9; Ptrend = 0.001 to 0.03). Results from replication set 2 were statistically homogeneous (Pheterogeneity≥0.13) and associated with increased risks at DCN rs3138165 and rs13312816, and LUM rs17018765: all ORs = 1.2; Ptrend≤0.02. The ORs at the four variants were statistically heterogeneous across all 18 studies (Pheterogeneity≤0.03), which precluded combining. In post-hoc analyses, interactions were observed between each variant and recruitment period (Pinteraction≤0.003), age at diagnosis (Pinteraction = 0.04), and year of diagnosis (Pinteraction = 0.05) in the five studies with available information (1,044 cases, 2,469 controls). We conclude that variants in DCN and LUM are not directly associated with sEOC, and that confirmation of possible effect modification of the variants by non-genetic factors is required.

Variations in TIMP3 are associated with age-related macular degeneration

Extracellular matrix (ECM) remodeling and degradation have been associated with atrophic changes in the retinal pigment epithelium (RPE) and Bruch's membrane, leading to macular dystrophy. In the paper based on a genome-wide association study (GWAS), Chen et al. (1) discovered a single-nucleotide polymorphism (SNP) located ≈100 kb upstream of TIMP3 that influenced the susceptibility to age-related macular degeneration (AMD) in very large and diverse cohorts. In an ongoing parallel effort, we undertook screening of 11 candidate genes involved in ECM turnover and degradation, namely fibulin 5 (FBLN5), fibulin 6 (FBLN6), decorin (DCN), lumican (LUM), epiphycan (EPYC), MMP1, MMP2, MMP3, MMP9, TIMP2, and TIMP3 to understand their involvement in a previously diagnosed cohort of AMD cases (n = 250) and normal controls (n = 250) from India (2).

Abstract 2854: Genetic variation in stromal genes decorin and lumican and susceptibility to serous ovarian cancer

Abstract Introduction: Alterations in components of the stromal tissue that underlie the epithelium can initiate, promote or inhibit epithelial tumorigenesis. Decorin (DCN) and lumican (LUM) are stromal genes with reduced expression in serous ovarian cancer. We hypothesized that single nucleotide polymorphisms (SNPs) in these genes may influence susceptibility to serous ovarian cancer. Methods: To test this hypothesis, we compared genotype frequencies of 11 tagSNPs in DCN and LUM between 397 Caucasian cases with primary serous ovarian cancer and 920 Caucasian controls in two studies conducted at Mayo Clinic and Duke University (discovery set). Associations were evaluated further in a third Caucasian population of 436 cases and 1,098 controls in Australia (replication set). TagSNPs were selected from unrelated Caucasian samples within HapMap based on the following criteria: (i) minor allele frequency ≥ 0.05, (ii) pairwise linkage disequilibrium (LD) of r2 ≥ 0.8, and (iii) location within, and 5kb upstream and downstream of, each gene region. Genotyping was performed using the Illumina GoldenGate™ assay and associations between SNPs and serous cancer were evaluated using unconditional logistic regression to estimate per allele odds ratios (OR) and 95% confidence intervals (95%CI). Untyped genotypes for DCN rs13312816 in the discovery set, and for DCN rs3138165 and LUM rs17018765 in the replication set, were imputed using the MACH software. Results: In the discovery set, we observed inverse associations between DCN rs3138165 (OR=0.7; 95%CI=0.5-1.0), DCN rs13312816 (OR=0.7; 95%CI=0.5-1.0), DCN rs516115 (OR=0.8; 95%CI=0.7-1.0) and LUM rs17018765 (OR=0.7; 95%CI=0.5-1.0) and risk of serous ovarian cancers (all Ptrend=0.06). Associations were confirmed in the replication set for DCN rs3138165 (OR=0.6; 95%CI=0.4-0.9; Ptrend=0.009), DCN rs13312816 (OR=0.7; 95%CI=0.5-0.9; Ptrend=0.01) and LUM rs17018765 (OR=0.6; 95%CI=0.4-0.9; Ptrend=0.008), but not for DCN rs516115 (Ptrend=0.20). To increase statistical power, data from the discovery and replication sets were combined (833 cases and 2,013 controls) following confirmation of no statistical heterogeneity in the ORs between study sites. In the combined sample, associations were strengthened for DCN rs3138165 (OR=0.7; 95%CI=0.5-0.9; Ptrend=0.002), DCN rs13312816 (OR=0.7; 95%CI=0.5-0.9; Ptrend=0.002), DCN rs516115 (OR=0.9; 95%CI=0.8-1.0; Ptrend=0.03) and LUM rs17018765 (OR=0.6; 95%CI=0.5-0.8; Ptrend=0.001). All four SNPs were in the same LD block on chromosome 12, suggesting that serous ovarian cancer susceptibility may be driven by a single, correlated variant in the region. Conclusion: The findings of this study suggest that genetic variation in DCN and LUM may influence susceptibility to serous ovarian cancer and contribute to the mounting evidence that supports the role of the stroma in epithelial ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2854.

Overexpression of Periostin and Lumican in Esophageal Squamous Cell Carcinoma

To identify biomarkers for early detection for esophageal squamous cell carcinoma (ESCC), we previously carried out a genome-wide gene expression profiling study using an oligonucleotide microarray platform. This analysis led to identification of several transcripts that were significantly upregulated in ESCC compared to the adjacent normal epithelium. In the current study, we performed immunohistochemical analyses of protein products for two candidates genes identified from the DNA microarray analysis, periostin (POSTN) and lumican (LUM), using tissue microarrays. Increased expression of both periostin and lumican was observed in 100% of 137 different ESCC samples arrayed on tissue microarrays. Increased expression of periostin and lumican was observed in carcinoma as well as in stromal cell in the large majority of cases. These findings suggest that these candidates can be investigated in the sera of ESCC patients using ELISA or multiple reaction monitoring (MRM) type assays to further explore their utility as biomarkers.

The association between lumican gene polymorphisms and high myopia

Lumican (LUM) is one of the major extracellular matrix components of the sclera. Increasing evidence suggests that changes in the structure and composition of the sclera are major factors in regulating scleral integrity and axial elongation of the eye, as in myopia. Patients (n=182; age range, 17-24 years) were with a myopic spherical equivalent (SE)>6.5 diopters (D) and the control group comprised individuals (n=78; age range, 17-25 years) were with a myopic SE<0.5 D. The DNA fragments were separated by horizontal electrophoresis on 3% agarose gels. The forward primer was labelled with a 5' FAM and the reaction products were detected using a 3100 Genetic Analyzer. The polymorphisms detected in this study were LUMc.601, LUM-59, LUM-628, and LUM-1554. Moreover, the haplotype distributions of Ht1 (C/A/CC/T), Ht2 (C/A/--/T), Ht3 (T/A/CC/C), Ht4 (T/--/CC/T), Ht5 (T/--/CC/C), and Ht6 (T/--/--/C) of these polymorphisms were compared between the two groups. The haplotype frequencies of Ht1, Ht2, Ht5, and Ht6 differed significantly between the two groups (P=2.08x10(-5), odds ratio (OR): 2.19, 95% confidence interval (CI): 1.52-3.15; P=2.2x10(-5), OR: 0.39, 95% CI: 0.25-0.61; P=2.7x10(-5), OR: 0.36, 95% CI: 0.22-0.59; P=3.7x10(-5), OR: 4.71, 95% CI: 2.12-10.5, respectively). These observations suggest that the four polymorphisms of the LUM promoter contribute to the pathogenesis of high myopia. Understanding the functions of LUM in myopia helps us design new methods in treating and preventing myopia.