Displaying publications 61 - 80 of 97 in total

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  1. Fulltext COVID-19 Infection and Circulating Microparticles-Reviewing Evidence as Microthrombogenic Risk Factor for Cerebral Small Vessel Disease
    Che Mohd Nassir CMN, Hashim S, Wong KK, Abdul Halim S, Idris NS, Jayabalan N, et al.
    Mol Neurobiol, 2021 Aug;58(8):4188-4215.
    PMID: 34176095 DOI: 10.1007/s12035-021-02457-z
    Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) due to novel coronavirus disease 2019 (COVID-19) has affected the global society in numerous unprecedented ways, with considerable morbidity and mortality. Both direct and indirect consequences from COVID-19 infection are recognized to give rise to cardio- and cerebrovascular complications. Despite current limited knowledge on COVID-19 pathogenesis, inflammation, endothelial dysfunction, and coagulopathy appear to play critical roles in COVID-19-associated cerebrovascular disease (CVD). One of the major subtypes of CVD is cerebral small vessel disease (CSVD) which represents a spectrum of pathological processes of various etiologies affecting the brain microcirculation that can trigger subsequent neuroinflammation and neurodegeneration. Prevalent with aging, CSVD is a recognized risk factor for stroke, vascular dementia, and Alzheimer's disease. In the background of COVID-19 infection, the heightened cellular activations from inflammations and oxidative stress may result in elevated levels of microthrombogenic extracellular-derived circulating microparticles (MPs). Consequently, MPs could act as pro-coagulant risk factor that may serve as microthrombi for the vulnerable microcirculation in the brain leading to CSVD manifestations. This review aims to appraise the accumulating body of evidence on the plausible impact of COVID-19 infection on the formation of microthrombogenic MPs that could lead to microthrombosis in CSVD manifestations, including occult CSVD which may last well beyond the pandemic era.
  2. Th1, Th2, and Th17 cytokines in systemic lupus erythematosus
    Muhammad Yusoff F, Wong KK, Mohd Redzwan N
    Autoimmunity, 2020 02;53(1):8-20.
    PMID: 31771364 DOI: 10.1080/08916934.2019.1693545
    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the breakdown of immune tolerance leading to excessive inflammation and tissue damage. Imbalance in the levels of cytokines represents one of the multifactorial causes of SLE pathogenesis and it contributes to disease severity. Deregulated levels of T helper type 1 (Th1), type 2 (Th2), and type 17 (Th17) cytokines have been associated with autoimmune inflammation. Growing evidence has shown deregulated levels of Th1, Th2, and Th17 cytokines in SLE patients compared to healthy controls associated with disease activity and severity. In this review, we describe and discuss the levels of Th1, Th2, and Th17 cytokines in SLE patients, and clinical trials involving Th1, Th2, and Th17 cytokines in SLE patients. In particular, with the exception of IL-2, IL-4, and TGF-β1, the levels of Th1, Th2, and Th17 cytokines are increased in SLE patients associated with disease severity. Current phase II or III studies involve therapeutic antibodies targeting IFN-α and type I IFN receptor, while low-dose IL-2 therapy is assessed in phase II clinical trials.
  3. Fulltext Zonula occludens-1 expression is reduced in nasal epithelial cells of allergic rhinitis patients
    Siti Sarah CO, Nur Husna SM, Md Shukri N, Wong KK, Mohd Ashari NS
    PeerJ, 2022;10:e13314.
    PMID: 35480562 DOI: 10.7717/peerj.13314
    Allergic rhinitis (AR) is a common allergic disease characterized by disruption of nasal epithelial barrier. In this study, we investigated the mRNA expression of zonula occludens-1 (ZO-1), ZO-2 and ZO-3 and histone deacetylase 1 (HDAC1) and HDAC2 in AR patients compared to healthy controls. RNA samples were extracted from nasal epithelial cells of house dust mites (HDMs)-sensitized AR patients and healthy controls (n = 28 in each group). The RNAs were reverse transcribed into cDNAs for measurement of ZO-1, ZO-2, ZO-3, HDAC1 and HDAC2 expression levels by quantitative PCR. The mRNA expression of ZO-1 was significantly decreased in AR patients compared to healthy controls (p = 0.010). No significant difference was observed in the expression levels of ZO-2, ZO-3, HDAC1 and HDAC2 in AR patients compared to healthy controls. We found significant associations of higher HDAC2 levels in AR patients with lower frequency of changing bedsheet (p = 0.043) and with AR patients sensitized to Dermatophagoides farinae (p = 0.041). Higher expression of ZO-2 was observed in AR patients who had pets (p = 0.007). In conclusion, our data indicated that ZO-1 expression was lower in AR patients contributing to decreased integrity of nasal epithelial barrier integrity, and HDAC2 may be involved in the pathogenesis of the disease.
  4. Fulltext Targeting dendritic cells through gold nanoparticles: A review on the cellular uptake and subsequent immunological properties
    Ahmad S, Zamry AA, Tan HT, Wong KK, Lim J, Mohamud R
    Mol Immunol, 2017 11;91:123-133.
    PMID: 28898717 DOI: 10.1016/j.molimm.2017.09.001
    Gold nanoparticles (NPs) have been proposed as a highly potential tool in immunotherapies due to its advantageous properties including customizable size and shapes, surface functionality and biocompatibility. Dendritic cells (DCs), the sentinels of immune response, have been of interest to be manipulated by using gold NPs for targeted delivery of immunotherapeutic agent. Researches done especially in human DCs showed a variation of gold NPs effects on cellular uptake and internalization, DC maturation and subsequent T cells priming as well as cytotoxicity. In this review, we describe the synthesis and physiochemical properties of gold NPs as well as the importance of gold NPs in immunotherapies through their actions on human DCs.
  5. Cancer/testis antigen SPATA19 is frequently expressed in benign prostatic hyperplasia and prostate cancer
    Wong KK, Hussain FA, Loo SK, López JI
    APMIS, 2017 Dec;125(12):1092-1101.
    PMID: 28972294 DOI: 10.1111/apm.12775
    Spermatogenesis-associated 19 (SPATA19) is a cancer/testis antigen overexpressed in various cancers. However, its protein expression profile in malignant or non-malignant tissues remains unknown. Thus, in this study, we investigated SPATA19 protein expression patterns in a panel of non-malignant human samples and primary prostate cancer (PCa) with or without benign prostatic hyperplasia (BPH) tissues. SPATA19 was absent in all non-malignant tissues investigated (n=14) except testis and prostate tissues. In terms of malignancies, all PCa cases were positive for SPATA19 exhibiting frequency between 20 and 100% (median 85%) with 63 (52.5%) and 57 (47.5%) cases demonstrating weak/moderate and strong intensities, respectively. Thirty-nine PCa cases (32.5%) contained BPH, and all BPH glands were SPATA19 positive (frequency between 20 and 100%; median 90%) with 13 (33.3%) demonstrating strong SPATA19 expression. Higher SPATA19 expression (higher frequency, intensity, or H-score) was not associated with overall survival or disease-specific survival (DFS) in all PCa cases. However, biochemical recurrence (BR) was associated with worse DFS (p = 0.005) in this cohort of 120 patients, and cases with strong SPATA19 intensity were associated with BR (p = 0.020). In conclusion, we showed that SPATA19 protein was frequently expressed in both BPH and PCa glands, and this warrants future investigations on its pathogenic roles in the disease.
  6. Histiocytosis X and vulvar ulceration
    Wong KK, Lin HP, Looi LM
    Int J Gynaecol Obstet, 1992 Oct;39(2):131-4.
    PMID: 1358712
    Vulvar ulceration is a rare manifestation of histiocytosis X. A 13-year-old girl had a nonhealing vulvar ulcer for 1 year. She had been in remission from histiocytosis X and the ulcer was not recognised as a sign of disease recurrence until tissue biopsy was obtained for histopathological and immunohistochemical studies. This article stresses the importance of establishing an accurate diagnosis when chronic vulvar ulcers are encountered and reviews the literature on this uncommon presentation of histiocytosis X.
  7. Fulltext Maternal and fetal outcomes of pregnant women with bacterial vaginosis
    Ng BK, Chuah JN, Cheah FC, Mohamed Ismail NA, Tan GC, Wong KK, et al.
    Front Surg, 2023;10:1084867.
    PMID: 36860946 DOI: 10.3389/fsurg.2023.1084867
    BACKGROUND: Bacterial vaginosis (BV) is a common infection in women of reproductive age group because of vaginal dysbiosis. The impact of BV during pregnancy is still not well defined. The objective of this study is to assess the maternal-fetal outcome in women with BV.

    MATERIALS AND METHODS: A prospective cohort study over one-year duration was conducted from December, 2014 until December, 2015, involving 237 women who presented with abnormal vaginal discharge, preterm labour or preterm prelabour rupture of membrane between 22- and 34-weeks period of gestation. Vaginal swabs were sent for culture and sensitivity, BV® Blue testing and PCR for Gardnerella vaginalis (GV).

    RESULTS: BV was diagnosed in 24/237 (10.1%) cases. The median gestational age was 31.6 weeks. GV was isolated from 16 out of 24 (66.7%) in the BV positive group. There was a significantly higher preterm birth rate, below 34 weeks (22.7% vs. 6.2%, p = 0.019) in women with BV. There was no statistically significant difference in maternal outcome such as clinical chorioamnionitis or endometritis. However, placental pathology revealed more than half (55.6%) of women with BV had histologic chorioamnionitis. Neonatal morbidity was significantly higher with exposure to BV, with a lower median birth weight, higher rate of neonatal intensive care unit admission (41.7% vs. 19.0%, p = 0.010), increased intubation for respiratory support (29.2% vs. 7.6%, p = 0.004) and respiratory distress syndrome (33.3% vs. 9.0%, p = 0.002).

    CONCLUSION: More research is needed to formulate guidelines for prevention, early detection and treatment of BV during pregnancy to reduce intrauterine inflammation and the associated adverse fetal outcomes.

  8. Fulltext GIFT triplets and management problems--a case report
    Wong KK, Lim CT
    Med J Malaysia, 1991 Sep;46(3):294-6.
    PMID: 1839929
    Pregnancies conceived through assisted reproduction can present considerable management problems to the obstetric and paediatric staff. Multiple pregnancies are common. The complication of prematurity increases the morbidity and mortality rates of the neonates.
  9. Fulltext [Anesthesia in anti-N-methyl-d-aspartate receptor encephalitis - is general anesthesia a requisite? A case report]
    Chaw SH, Foo LL, Chan L, Wong KK, Abdullah S, Lim BK
    Rev Bras Anestesiol, 2016 09 28;67(6):647-650.
    PMID: 27687317 DOI: 10.1016/j.bjan.2016.09.003
    Anti-N-methyl-d-aspartate receptor encephalitis is a recently described neurological disorder and an increasingly recognized cause of psychosis, movement disorders and autonomic dysfunction. We report 20-year-old Chinese female who presented with generalized tonic-clonic seizures, recent memory loss, visual hallucinations and abnormal behavior. Anti-N-methyl-d-aspartate receptor encephalitis was diagnosed and a computed tomography scan of abdomen reviewed a left adnexal tumor. We describe the first such case report of a patient with anti-N-methyl-d-aspartate receptor encephalitis who was given a bilateral transversus abdominis plane block as the sole anesthetic for removal of ovarian tumor. We also discuss the anesthetic issues associated with anti-N-methyl-d-aspartate receptor encephalitis. As discovery of tumor and its removal is the focus of initial treatment in this group of patients, anesthetists will encounter more such cases in the near future.
  10. Low HIP1R mRNA and protein expression are associated with worse survival in diffuse large B-cell lymphoma patients treated with R-CHOP
    Wong KK, Ch'ng ES, Loo SK, Husin A, Muruzabal MA, Møller MB, et al.
    Exp Mol Pathol, 2015 Dec;99(3):537-45.
    PMID: 26341140 DOI: 10.1016/j.yexmp.2015.08.019
    Huntingtin-interacting protein 1-related (HIP1R) is an endocytic protein involved in receptor trafficking, including regulating cell surface expression of receptor tyrosine kinases. We have previously shown that low HIP1R protein expression was associated with poorer survival in diffuse large B-cell lymphoma (DLBCL) patients from Denmark treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). In this multicenter study, we extend these findings and validate the prognostic and subtyping utility of HIP1R expression at both transcript and protein level. Using data mining on three independent transcriptomic datasets of DLBCL, HIP1R transcript was preferentially expressed in germinal center B-cell (GCB)-like DLBCL subtype (P<0.01 in all three datasets), and lower expression was correlated with worse overall survival (OS; P<0.01) and progression-free survival (PFS; P<0.05) in a microarray-profiled DLBCL dataset. At the protein level examined by immunohistochemistry, HIP1R expression at 30% cut-off was associated with GCB-DLBCL molecular subtype (P=0.0004; n=42), and predictive of OS (P=0.0006) and PFS (P=0.0230) in de novo DLBCL patients treated with R-CHOP (n=73). Cases with high FOXP1 and low HIP1R expression frequency (FOXP1(hi)/HIP1R(lo) phenotype) exhibited poorer OS (P=0.0038) and PFS (P=0.0134). Multivariate analysis showed that HIP1R<30% or FOXP1(hi)/HIP1R(lo) subgroup of patients exhibited inferior OS and PFS (P<0.05) independently of the International Prognostic Index. We conclude that HIP1R expression is strongly indicative of survival when utilized on its own or in combination with FOXP1, and the molecule is potentially applicable for subtyping of DLBCL cases.
  11. Optimization of circular plate separators with cross flow for removal of oil droplets and solid particles
    Ngu H, Wong KK, Law PL
    Water Environ Res, 2012 Apr;84(4):299-304.
    PMID: 22834217
    A circular gravity-phase separator using coalescing medium with cross flow was developed to remove oil and suspended solids from wastewaters. Coalescence medium in the form of inclined plates promotes rising of oil droplets through coalescence and settling of solid particles through coagulation. It exhibits 22.67% higher removal of total suspended solids (TSS) compared to separators without coalescing medium. Moreover, it removed more than 70% of oil compared to conventional American Petroleum Institute separators, which exhibit an average of 33% oil removal. The flowrate required to attain an effluent oil concentration of 10 mg/L (Q(o10)) at different influent oil concentrations (C(io)) can be represented by Q(o10) x 10(-5) = -0.0012C(io) + 0.352. The flowrate required to attain an effluent TSS concentration of 50 mg/L (Q(ss50)) at different influent TSS concentrations (C(iss)) can be represented by Q(ss50) x 10(-5) = 1.0 x 10(6) C(iss)(-2.9576). The smallest removable solid particle size was 4.87 microm.
  12. Fulltext Development of an effective clustering algorithm for older fallers
    Goh CH, Wong KK, Tan MP, Ng SC, Chuah YD, Kwan BH
    PLoS One, 2022;17(11):e0277966.
    PMID: 36441703 DOI: 10.1371/journal.pone.0277966
    Falls are common and often lead to serious physical and psychological consequences for older persons. The occurrence of falls are usually attributed to the interaction between multiple risk factors. The clinical evaluation of falls risks is time-consuming as a result, hence limiting its availability. The purpose of this study was, therefore, to develop a clustering-based algorithm to determine falls risk. Data from the Malaysian Elders Longitudinal Research (MELoR), comprising 1411 subjects aged ≥55 years, were utilized. The proposed algorithm was developed through the stages of: data pre-processing, feature identification and extraction with either t-Distributed Stochastic Neighbour Embedding (t-SNE) or principal component analysis (PCA)), clustering (K-means clustering, Hierarchical clustering, and Fuzzy C-means clustering) and characteristics interpretation with statistical analysis. A total of 1279 subjects and 9 variables were selected for clustering after the data pre-possessing stage. Using feature extraction with the t-SNE and the K-means clustering algorithm, subjects were clustered into low, intermediate A, intermediate B and high fall risk groups which corresponded with fall occurrence of 13%, 19%, 21% and 31% respectively. Slower gait, poorer balance, weaker muscle strength, presence of cardiovascular disorder, poorer cognitive performance, and advancing age were the key variables identified. The proposed fall risk clustering algorithm grouped the subjects according to features. Such a tool could serve as a case identification or clinical decision support tool for clinical practice to enhance access to falls prevention efforts.
  13. Fulltext N-Acetylcysteine as Adjuvant Therapy for COVID-19 - A Perspective on the Current State of the Evidence
    Wong KK, Lee SWH, Kua KP
    J Inflamm Res, 2021;14:2993-3013.
    PMID: 34262324 DOI: 10.2147/JIR.S306849
    The looming severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a long-lasting pandemic of coronavirus disease 2019 (COVID-19) around the globe with substantial morbidity and mortality. N-acetylcysteine, being a nutraceutical precursor of an important antioxidant glutathione, can perform several biological functions in mammals and microbes. It has consequently garnered a growing interest as a potential adjunctive therapy for coronavirus disease. Here, we review evidence concerning the effects of N-acetylcysteine in respiratory viral infections based on currently available in vitro, in vivo, and human clinical investigations. The repurposing of a known drug such as N-acetylcysteine may significantly hasten the deployment of a novel approach for COVID-19. Since the drug candidate has already been translated into the clinic for several decades, its established pharmacological properties and safety and side-effect profiles expedite preclinical and clinical assessment for the treatment of COVID-19. In vitro data have depicted that N-acetylcysteine increases antioxidant capacity, interferes with virus replication, and suppresses expression of pro-inflammatory cytokines in cells infected with influenza viruses or respiratory syncytial virus. Furthermore, findings from in vivo studies have displayed that, by virtue of immune modulation and anti-inflammatory mechanism, N-acetylcysteine reduces the mortality rate in influenza-infected mice animal models. The promising in vitro and in vivo results have prompted the initiation of human subject research for the treatment of COVID-19, including severe pneumonia and acute respiratory distress syndrome. Albeit some evidence of benefits has been observed in clinical outcomes of patients, precision nanoparticle design of N-acetylcysteine may allow for greater therapeutic efficacy.
  14. Effect of the oral contraceptive pill on protein S and antithrombin-III levels in Malaysian women
    Wong KK, Ng SC, Koong PL
    Med Sci Res, 1992 Jun;20(12):439-40.
    PMID: 12288974
  15. Comparative transcriptomic profiling in HPV-associated cervical carcinogenesis: Implication of MHC class II and immunoglobulin heavy chain genes
    Balasubramaniam SD, Wong KK, Oon CE, Balakrishnan V, Kaur G
    Life Sci, 2020 Sep 01;256:118026.
    PMID: 32615187 DOI: 10.1016/j.lfs.2020.118026
    AIM: We aimed to determine the biological processes and pathways involved in cervical carcinogenesis associated with high-risk human papillomavirus (HPV) infection.

    MATERIALS AND METHODS: Total RNA was extracted from three formalin-fixed paraffin-embedded (FFPE) samples each of normal cervix, HPV-infected low-grade squamous intraepithelial lesion (LSIL), high-grade SIL (HSIL) and squamous cell carcinoma (SCC). Transcriptomic profiling by microarrays was conducted followed by downstream Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.

    RESULTS: We examined the difference in GOs enriched for each transition stage from normal cervix to LSIL, HSIL, and SCC, and found 307 genes to be differentially expressed. In the transition from normal cervix to LSIL, the extracellular matrix (ECM) genes were significantly downregulated. The MHC class II genes were significantly upregulated in the LSIL to HSIL transition. In the final transition from HSIL to SCC, the immunoglobulin heavy locus genes were significantly upregulated and the ECM pathway was implicated.

    CONCLUSION: Deregulation of the immune-related genes including MHC II and immunoglobulin heavy chain genes were involved in the transitions from LSIL to HSIL and SCC, suggesting immune escape from host anti-tumour response. The extracellular matrix plays an important role during the early and late stages of cervical carcinogenesis.

  16. Humidity versus photo-stability of metal halide perovskite films in a polymer matrix
    Manshor NA, Wali Q, Wong KK, Muzakir SK, Fakharuddin A, Schmidt-Mende L, et al.
    Phys Chem Chem Phys, 2016 Aug 21;18(31):21629-39.
    PMID: 27432518 DOI: 10.1039/c6cp03600g
    Despite the high efficiency of over 21% reported for emerging thin film perovskite solar cells, one of the key issues prior to their commercial deployment is to attain their long term stability under ambient and outdoor conditions. The instability in perovskite is widely conceived to be humidity induced due to the water solubility of its initial precursors, which leads to decomposition of the perovskite crystal structure; however, we note that humidity alone is not the major degradation factor and it is rather the photon dose in combination with humidity exposure that triggers the instability. In our experiment, which is designed to decouple the effect of humidity and light on perovskite degradation, we investigate the shelf-lifetime of CH3NH3PbI3 films in the dark and under illumination under high humidity conditions (Rel. H. > 70%). We note minor degradation in perovskite films stored in a humid dark environment whereas upon exposure to light, the films undergo drastic degradation, primarily owing to the reactive TiO2/perovskite interface and also the surface defects of TiO2. To enhance its air-stability, we incorporate CH3NH3PbI3 perovskite in a polymer (poly-vinylpyrrolidone, PVP) matrix which retained its optical and structural characteristics in the dark for ∼2000 h and ∼800 h in room light soaking, significantly higher than a pristine perovskite film, which degraded completely in 600 h in the dark and in less than 100 h when exposed to light. We attribute the superior stability of PVP incorporated perovskite films to the improved structural stability of CH3NH3PbI3 and also to the improved TiO2/perovskite interface upon incorporating a polymer matrix. Charge injection from the polymer embedded perovskite films has also been confirmed by fabricating solar cells using them, thereby providing a promising future research pathway for stable and efficient perovskite solar cells.
  17. Fulltext Influenza and Respiratory Syncytial viral infections in Malaysia: Demographic and Clinical perspective
    Rahman MM, Wong KK, Hanafiah A, Isahak I
    Pak J Med Sci, 2014 Jan;30(1):161-5.
    PMID: 24639853 DOI: 10.12669/pjms.301.4272
    Respiratory infections represent a major public health problem worldwide. The study aimed to determine the prevalence of respiratory syncytial and influenza virus infections and analyzed in respect to demography and clinical perspective. Methods : The specimens were processed by cell culture and immunofluorescent assay (IFA) and real-time reverse transcriptase-PCR (rRT-PCR) for detection of respiratory viruses. Results : Out of 505 specimens 189 (37.8%) were positive, in which RSV was positive in 124(24.8%) cases and influenza A was positive in 65(13%) cases. Positive cases for influenza virus A and RSV were analyzed based on demography: age, gender, ethnicity and clinical symptoms. There were no significant differences among gender, ethnicity and clinical symptoms in both RSV and influenza A virus infections. It was observed that children below 3 years of ages were more prone to RSV infections. On the contrary, influenza virus A infected all age groups of humans.
  18. Fulltext Influenza and respiratory syncytial viruses: Efficacy of different diagnostic assays
    Rahman MM, Wong KK, Alfizah H, Hussin S, Isahak I
    Pak J Med Sci, 2015 Jul-Aug;31(4):791-4.
    PMID: 26430404 DOI: 10.12669/pjms.314.7003
    To determine the efficacy of cell culture, immunoflourescence Assay (IFA) and real time polymerase chain reaction (rRT-PCR) in relation to diagnosis of influenza and Respiratory Syncytial Virus (RSV).
  19. Fulltext Preliminary evaluation of various rapid influenza diagnostic test methods for the detection of the novel influenza A (H1N1) in Universiti Kebangsaan Malaysia Medical Centre
    Zetti ZR, Wong KK, Haslina M, Ilina I
    Med J Malaysia, 2010 Mar;65(1):27-30.
    PMID: 21265244 MyJurnal
    We evaluated the performance of four rapid influenza diagnostic test methods (RIDT) compared to real-time reverse-transcription polymerase chain reaction (rRT-PCR), for the detection of the novel swine-origin influenza A (H1N1) virus (S-OIV) in August 2009. A total of 270 respiratory specimens were tested with rRT-PCR, where 74 of these were tested by BinaxNow (Inverness), 80 by QuickVue (Quidel), 37 by Influenza A Antigen Rapid Test (Rockeby Biomed) and 79 by Directigen (BD). The sensitivities ranged from 4.4% to 37.0%, specificities 90.9% to 100.0%, positive predictive values 75.0% to 100.0% and negative predictive values 32.3% to 75.0%. RIDT were able to detect S-OIV but the sensitivities were low. The limitations of RIDT must be considered when interpreting results for clinical management.
  20. Fulltext TRPM4 is overexpressed in breast cancer associated with estrogen response and epithelial-mesenchymal transition gene sets
    Wong KK, Hussain FA
    PLoS One, 2020;15(6):e0233884.
    PMID: 32484822 DOI: 10.1371/journal.pone.0233884
    Ion channels form an important class of drug targets in malignancies. Transient receptor potential cation channel subfamily M member 4 (TRPM4) plays oncological roles in various solid tumors. Herein, we examined TRPM4 protein expression profile by immunohistochemistry (IHC) in breast cancer cases compared with normal breast ducts, its association with clinico-demographical parameters, and its potential function in breast cancers by Gene Set Enrichment Analysis (GSEA). Data-mining demonstrated that TRPM4 transcript levels were significantly higher in The Cancer Genome Atlas series of breast cancer cases (n = 1,085) compared with normal breast tissues (n = 112) (p = 1.03 x 10-11). Our IHC findings in tissue microarrays showed that TRPM4 protein was overexpressed in breast cancers (n = 83/99 TRPM4+; 83.8%) compared with normal breast ducts (n = 5/10 TRPM4+; 50%) (p = 0.022). Higher TRPM4 expression (median frequency cut-off) was significantly associated with higher lymph node status (N1-N2 vs N0; p = 0.024) and higher stage (IIb-IIIb vs I-IIa; p = 0.005). GSEA evaluation in three independent gene expression profiling (GEP) datasets of breast cancer cases (GSE54002, n = 417; GSE20685, n = 327; GSE23720, n = 197) demonstrated significant association of TRPM4 transcript expression with estrogen response and epithelial-mesenchymal transition (EMT) gene sets (p<0.01 and false discovery rate<0.05). These gene sets were not enriched in GEP datasets of normal breast epithelium cases (GSE10797, n = 5; GSE9574, n = 15; GSE20437, n = 18). In conclusion, TRPM4 protein expression is upregulated in breast cancers associated with worse clinico-demographical parameters, and TRPM4 potentially regulates estrogen receptor signaling and EMT progression in breast cancer.
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