Displaying publications 1 - 20 of 97 in total

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  1. 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.
  2. Baraya YS, Wong KK, Yaacob NS
    Anticancer Agents Med Chem, 2017;17(6):770-783.
    PMID: 27539316 DOI: 10.2174/1871520616666160817111242
    Breast cancer has continued to cause high cancer death rates among women worldwide. The use of plants' natural products in breast cancer treatment has received more attention in recent years due to their potentially wider safety margin and the potential to complement conventional chemotherapeutic drugs. Plantbased products have demonstrated anticancer potential through different biological pathways including modulation of the immune system. Immunomodulatory properties of medicinal plants have been shown to mitigate breast cancer cell growth. Different immune cell types participate in this process especially cytotoxic T cells and natural killer cells, and cytokines including chemokines and tumor necrosis factor-α. Medicinal plants such as Glycyrrhiza glabra, Uncaria tomentosa, Camellia sinensis, Panax ginseng, Prunus armenaica (apricot), Allium sativum, Arctium lappa and Curcuma longa were reported to hold strong potential in breast cancer treatment in various parts of the world. Interestingly, research findings have shown that these plants possess bioactive immunomodulators as their main constituents producing the anticancer effects. These immunomodulatory compounds include ajoene, arctigenin, β-carotene, curcumin, epigallocatechin-3-gallate, ginsan, glabridin and quinic acid. In this review, we discussed the ability of these eight immunomodulators in regulating the immune system potentially applicable in breast cancer treatment via anti-inflammatory (curcumin, arctigenin, glabridin and ajoene) and lymphocytes activation (β-carotene, epigallocatechin-3-gallate, quinic acid and ginsan) properties, as well as future research direction in their use for breast cancer treatment.
  3. Perera D, Yusof MA, Podin Y, Ooi MH, Thao NT, Wong KK, et al.
    Arch Virol, 2007;152(6):1201-8.
    PMID: 17308978
    A phylogenetic analysis of VP1 and VP4 nucleotide sequences of 52 recent CVA16 strains demonstrated two distinct CVA16 genogroups, A and B, with the prototype strain being the only member of genogroup A. CVA16 G-10, the prototype strain, showed a nucleotide difference of 27.7-30.2% and 19.9-25.2% in VP1 and VP4, respectively, in relation to other CVA16 strains, which formed two separate lineages in genogroup B with nucleotide variation of less than 13.4% and less than 16.3% in VP1 and VP4, respectively. Lineage 1 strains circulating before 2000 were later displaced by lineage 2 strains.
  4. Lim CT, Wong KK, Yap YF, Sivanesaratnam V
    Asia Oceania J Obstet Gynaecol, 1992 Mar;18(1):19-22.
    PMID: 1627057
    Large ovarian cysts in the fetus are uncommon. Ultrasonography has helped in the detection of these cysts antenatally and in the newborn female infant. A case of bilateral ovarian cysts in a newborn is presented. The choice of management between conservative measures and surgical approaches remains controversial.
  5. Wong KK, Ng KH, Nah SH, Yusof K, Rajeswari K
    Asia Oceania J Obstet Gynaecol, 1994 Mar;20(1):19-23.
    PMID: 8172522
    The general lack of specialist obstetricians in a developing country such as Malaysia prompted us to develop a computer expert system for the management of fetal distress in rural hospitals. It was based on accepted production rules and implemented on a microcomputer. The clinical prototype was evaluated by 8 specialist obstetricians and 21 non-specialist doctors involved in obstetric care. The initial impression was that this type of expert system may help in diagnosis, decision-making and teaching.
  6. Sani MM, Ashari NSM, Abdullah B, Wong KK, Musa KI, Mohamud R, et al.
    Asian Pac J Allergy Immunol, 2019 Sep;37(3):138-146.
    PMID: 29981564 DOI: 10.12932/AP-191217-0220
    BACKGROUND: Terminally differentiated effector memory (TEMRA) T cells exert potent effector function after activation. The proportions of CD4+ T cell subsets especially memory cells in allergic rhinitis (AR) patients sensitized to house dust mites (HDMs) have not been extensively studied.

    OBJECTIVE: This study aimed to compare the mean percentages and absolute counts of CD4+ memory T cell subsets between: (i) non-allergic controls and AR patients; (ii) mild AR patients and moderate-severe AR patients.

    METHODS: Sensitization to Dermatophagoides farinae and Dermatophagoides pteronyssinus were determined in 33 non -allergic controls, 28 mild AR and 29 moderate-severe AR patients. Flow cytometry was used to determine the percentage of CD4+ na?ve (TN; CD45RA+CCR7+), central memory (TCM; CD45RA-CCR7+), effector memory (TEM; CD45RA-CCR7-) and TEMRA (CD45RA+CCR7-) T cells from the peripheral blood. The absolute counts of CD4+ T cell subsets were obtained by dual platform method from flow cytometer and hematology analyzer.

    RESULTS: There were no significant differences in the mean percentages and absolute counts of CD4+ T cell subsets between non-allergic controls and AR patients sensitized to HDMs. However, there were significant reduction in the mean percentage (p=0.0307) and absolute count (p=0.0309) of CD4+ TEMRA cells in moderate-severe AR patients compared to mild AR patients sensitized to HDMs and 13/24 (54.2%) moderate-severe AR patients sensitized to HDMs had persistent symptoms.

    CONCLUSION: Reduction in the mean percentage and absolute count of CD4+CD45RA+CCR7- TEMRA cells were observed in moderate-severe AR patients compared to mild AR patients in our population of AR patients sensitized to HDMs.

  7. Yaacob NS, Nik Mohamed Kamal NN, Wong KK, Norazmi MN
    Asian Pac J Cancer Prev, 2015;16(18):8135-40.
    PMID: 26745050
    BACKGROUND: Cell cycle regulatory proteins are suitable targets for cancer therapeutic development since genetic alterations in many cancers also affect the functions of these molecules. Strobilanthes crispus (S. crispus) is traditionally known for its potential benefits in treating various ailments. We recently reported that an active sub-fraction of S. crispus leaves (SCS) caused caspase-dependent apoptosis of human breast cancer MCF-7 and MDA-MB-231 cells.

    MATERIALS AND METHODS: Considering the ability of SCS to also promote the activity of the antiestrogen, tamoxifen, we further examined the effect of SCS in modulating cell cycle progression and related proteins in MCF-7 and MDA-MB-231 cells alone and in combination with tamoxifen. Expression of cell cycle- related transcripts was analysed based on a previous microarray dataset.

    RESULTS: SCS significantly caused G1 arrest of both types of cells, similar to tamoxifen and this was associated with modulation of cyclin D1, p21 and p53. In combination with tamoxifen, the anticancer effects involved downregulation of ERα protein in MCF-7 cells but appeared independent of an ER-mediated mechanism in MDA-MB-231 cells. Microarray data analysis confirmed the clinical relevance of the proteins studied.

    CONCLUSIONS: The current data suggest that SCS growth inhibitory effects are similar to that of the antiestrogen, tamoxifen, further supporting the previously demonstrated cytotoxic and apoptotic actions of both agents.

  8. 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.
  9. Islam MA, Alam F, Wong KK
    Autoimmun Rev, 2017 May;16(5):512-522.
    PMID: 28279839 DOI: 10.1016/j.autrev.2017.03.005
    BACKGROUND: Antiphospholipid antibodies (aPLs) namely anticardiolipin (aCL) antibody, anti-β2-glycoprotein I (β2GPI) antibody and lupus anticoagulant (LA) are autoantibodies produced against anionic phospholipids and proteins on plasma membranes. Migraine is a primary headache disorder which has growing evidences of autoimmune-mediated pathogenesis and previous studies suggested the presence of aPLs in migraine patients.

    AIMS: The aim of this study was to evaluate the comorbid association between aPLs (aCL, anti-β2GPI and LA) and migraine compared to healthy controls.

    METHODS: Studies were searched through PubMed, ISI Web of Science and Google Scholar databases without restricting the languages and year (up to October 2016) and were selected based on the inclusion criteria. Two authors independently extracted data from the included studies. All analyses were conducted by using random effects model to calculate the odds ratio (OR) and 95% confidence interval (CI). Quality assessment was carried out by using the modified Newcastle-Ottawa Scale (NOS). Publication bias was evaluated via visualization of funnel plots, Begg's and Egger's tests.

    RESULTS: The database searches produced 1995 articles, 13 of which were selected (912 migraineurs and 822 healthy controls). 8.59%, 15.21% and 4.11% of the migraineurs exhibited aCL, anti-β2GPI and LA which was 4.83, 1.63 and 3.03 times higher, respectively, than healthy controls. A significant presence of aCL (OR: 3.55, 95% CI: 1.59-7.95; p=0.002) or anti-β2GPI antibodies (OR: 2.02, 95% CI: 1.20-3.42; p=0.008) was observed in migraine patients, however, LA was not significantly associated (OR: 2.02, 95% CI: 0.50-8.37; p=0.320). Majority of the studies (n=10 of 13) demonstrated NOS score of 7 or above and no significant publication bias was observed.

    CONCLUSION: Migraine might be an autoimmune-associated neurologic disorder. The presence of aCL or anti-β2GPI antibodies was significant in migraine patients compared to healthy controls, suggesting an involvement of these autoantibodies in migraine attack.
  10. Yip KF, Rai V, Wong KK
    BMC Anesthesiol, 2014;14:127.
    PMID: 25587238 DOI: 10.1186/1471-2253-14-127
    There are numerous challenges in providing nutrition to the mechanically ventilated critically ill ICU patient. Understanding the level of nutritional support and the barriers to enteral feeding interruption in mechanically ventilated patients are important to maximise the nutritional benefits to the critically ill patients. Thus, this study aims to evaluate enteral nutrition delivery and identify the reasons for interruptions in mechanically ventilated Malaysian patients receiving enteral feeding.
  11. Rai V, Shariffuddin II, Chan YK, Muniandy RK, Wong KK, Singh S
    BMC Anesthesiol, 2014;14:49.
    PMID: 25002831 DOI: 10.1186/1471-2253-14-49
    BACKGROUND: Complete heart block in pregnancy has serious implications particularly during the period of delivery. This is more so if the delivery is an operative one as the presence of heart block may produce haemodynamic instability in the intra operative period. We report a unique case of a pregnant mother with complete heart block undergoing hysterostomy, complicated by placenta accreta and intrauterine death.

    CASE PRESENTATION: A 37 year old Malaysian Chinese parturient was admitted at 25 weeks gestation following a scan which suggested intrauterine death and placenta accreta. She was diagnosed to have congenital complete heart block after her first delivery eight years previously but a pacemaker was never inserted. These medical conditions make her extremely likely to experience massive bleeding and haemodynamic instability. Among the measures taken to optimise her pre-operatively were the insertion of a temporary intravenous pacemaker and embolization of the uterine arteries to minimize peri-operative blood loss. She successfully underwent surgery under general anesthesia, which was relatively uneventful and was discharged well on the fourth post-operative day.

    CONCLUSION: Congenital heart block in pregnancies in the presence of potential massive bleeding is best managed by a team, with meticulous pre-operative optimization. Suggested strategies would include insertion of a temporary pacemaker and embolization of the uterine arteries to reduce the risk of the patient getting into life threatening situations.

  12. Swaminathan A, Abd Aziz NH, Ayub NA, Wong KK, Cheah FC
    BMC Res Notes, 2021 Nov 22;14(1):420.
    PMID: 34809696 DOI: 10.1186/s13104-021-05842-y
    OBJECTIVE: Pregnant women with bacterial vaginosis due to Gardnerella vaginalis (GV) infection presents with a wide-ranging disease symptomatology. We speculate this may be due to interaction that varies between host immune response and the pathogen. We studied the oxidative burst in polymorphonuclear leukocytes (PMNL)s from maternal blood (MB) and cord blood (CB) upon phagocytosis of GV and compared against E. coli and Group B Streptococcus (GBS).

    RESULTS: The PHAGOBURST™ assay detects fluorescence from oxidized dihydrorhodamine during oxidative burst. The average percentage of PMNL showing oxidative burst was almost two-fold greater with GBS (99.5%) and E. coli (98.2%) than GV (56.9%) (p 

  13. Patel S, Murphy D, Haralambieva E, Abdulla ZA, Wong KK, Chen H, et al.
    Biomark Insights, 2014;9:77-84.
    PMID: 25232277 DOI: 10.4137/BMI.S16553
    FAS-associated protein with death domain (FADD) is a major adaptor protein involved in extrinsic apoptosis, embryogenesis, and lymphocyte homeostasis. Although abnormalities of the FADD/death receptor apoptotic pathways have been established in tumorigenesis, fewer studies have analyzed the expression and role of phosphorylated FADD (pFADD). Our identification of FADD as a lymphoma-associated autoantigen in T-cell lymphoma patients raises the possibility that pFADD, with its correlation with cell cycle, may possess role(s) in human T-cell lymphoma development. This immunohistochemical study investigated pFADD protein expression in a range of normal tissues and lymphomas, particularly T-cell lymphomas that require improved therapies. Whereas pFADD was expressed only in scattered normal T cells, it was detected at high levels in T-cell lymphomas (eg, 84% anaplastic large cell lymphoma and 65% peripheral T cell lymphomas, not otherwise specified). The increased expression of pFADD supports further study of its clinical relevance and role in lymphomagenesis, highlighting phosphorylation of FADD as a potential therapeutic target.
  14. Wong KK, Lawrie CH, Green TM
    Biomark Insights, 2019;14:1177271919846454.
    PMID: 31105426 DOI: 10.1177/1177271919846454
    Epigenetic alteration has been proposed to give rise to numerous classic hallmarks of cancer. Impaired DNA methylation plays a central role in the onset and progression of several types of malignancies, and DNA methylation is mediated by DNA methyltransferases (DNMTs) consisting of DNMT1, DNMT3A, and DNMT3B. DNMTs are frequently implicated in the pathogenesis and aggressiveness of acute myeloid leukaemia (AML) patients. In this review, we describe and discuss the oncogenic roles of DNMT1, DNMT3A, and DNMT3B in AML. The clinical response predictive roles of DNMTs in clinical trials utilising hypomethylating agents (azacitidine and decitabine) in AML patients are presented. Novel hypomethylating agent (guadecitabine) and experimental DNMT inhibitors in AML are also discussed. In summary, hypermethylation of tumour suppressors mediated by DNMT1 or DNMT3B contributes to the progression and severity of AML (except MLL-AF9 and inv(16)(p13;q22) AML for DNMT3B), while mutation affecting DNMT3A represents an early genetic lesion in the pathogenesis of AML. In clinical trials of AML patients, expression of DNMTs is downregulated by hypomethylating agents while the clinical response predictive roles of DNMT biomarkers remain unresolved. Finally, nucleoside hypomethylating agents have continued to show enhanced responses in clinical trials of AML patients, and novel non-nucleoside DNMT inhibitors have demonstrated cytotoxicity against AML cells in pre-clinical settings.
  15. Islam MA, Alam F, Kamal MA, Wong KK, Sasongko TH, Gan SH
    CNS Neurol Disord Drug Targets, 2016;15(10):1253-1265.
    PMID: 27658514 DOI: 10.2174/1871527315666160920122750
    Neurological manifestations or disorders associated with the central nervous system are among the most common and important clinical characteristics of antiphospholipid syndrome (APS). Although in the most recently updated (2006) APS classification criteria, the neurological manifestations encompass only transient ischemic attack and stroke, diverse 'non-criteria' neurological disorders or manifestations (i.e., headache, migraine, bipolar disorder, transverse myelitis, dementia, chorea, epileptic seizures, multiple sclerosis, psychosis, cognitive impairment, Tourette's syndrome, parkinsonism, dystonia, transient global amnesia, obsessive compulsive disorder and leukoencephalopathy) have been observed in APS patients. To date, the underlying mechanisms responsible for these abnormal neurological manifestations in APS remain unclear. In vivo experiments and human observational studies indicate the involvement of thrombotic events and/or high titers of antiphospholipid antibodies in the neuro-pathogenic cascade of APS. Although different types of neurologic manifestations in APS patients have successfully been treated with therapies involving anti-thrombotic regimens (i.e., anticoagulants and/or platelet antiaggregants), antineuralgic drugs (i.e., antidepressants, antipsychotics and antiepileptics) and immunosuppressive drugs alone or in combination, evidence-based guidelines for the management of the neurologic manifestations of APS remain unavailable. Therefore, further experimental, clinical and retrospective studies with larger patient cohorts are warranted to elucidate the pathogenic linkage between APS and the central nervous system in addition to randomized controlled trials to facilitate the discovery of appropriate medications for the 'non-criteria' neurologic manifestations of APS.
  16. Wong KK
    Cell Oncol (Dordr), 2020 Oct;43(5):779-792.
    PMID: 32504382 DOI: 10.1007/s13402-020-00526-4
    BACKGROUND: Pancreatic cancer or pancreatic ductal adenocarcinoma (PDAC) is one of the most devastating cancer types with a 5-year survival rate of only 9%. PDAC is one of the leading causes of cancer-related deaths in both genders. Epigenetic alterations may lead to the suppression of tumor suppressor genes, and DNA methylation is a predominant epigenetic modification. DNA methyltransferase 1 (DNMT1) is required for maintaining patterns of DNA methylation during cellular replication. Accumulating evidence has implicated the oncogenic roles of DNMT1 in various malignancies including PDACs.

    CONCLUSIONS: Herein, the expression profiles, oncogenic roles, regulators and inhibitors of DNMT1 in PDACs are presented and discussed. DNMT1 is overexpressed in PDAC cases compared with non-cancerous pancreatic ducts, and its expression gradually increases from pre-neoplastic lesions to PDACs. DNMT1 plays oncogenic roles in suppressing PDAC cell differentiation and in promoting their proliferation, migration and invasion, as well as in induction of the self-renewal capacity of PDAC cancer stem cells. These effects are achieved via promoter hypermethylation of tumor suppressor genes, including cyclin-dependent kinase inhibitors (e.g., p14, p15, p16, p21 and p27), suppressors of epithelial-mesenchymal transition (e.g., E-cadherin) and tumor suppressor miRNAs (e.g., miR-148a, miR-152 and miR-17-92 cluster). Pre-clinical investigations have shown the potency of novel non-nucleoside DNMT1 inhibitors against PDAC cells. Finally, phase I/II clinical trials of DNMT1 inhibitors (azacitidine, decitabine and guadecitabine) in PDAC patients are currently underway, where these inhibitors have the potential to sensitize PDACs to chemotherapy and immune checkpoint blockade therapy.

  17. Islam MA, Alam F, Gan SH, Cavestro C, Wong KK
    Cephalalgia, 2018 03;38(3):568-580.
    PMID: 28952322 DOI: 10.1177/0333102417694881
    Background The occurrence of antiphospholipid antibodies (aPLs) and headache comorbidity in the presence or absence of underlying autoimmune diseases remains unclear. Aim The aim of this review was to summarize the relationship between headache and aPLs based on evidences from cohort studies and case reports, in addition to examining the treatment strategies that resolved headache in aPLs-positive individuals.
    Methods A comprehensive literature search was conducted through PubMed, ISI Web of Science and Google Scholar. A total of 559 articles were screened and the appropriate articles were selected based on quality and level of evidence.
    Results Cohort studies (n = 27) from Europe, North America and Asia demonstrated comorbidity of aPLs and headache in antiphospholipid syndrome, systemic lupus erythematosus (SLE) and neuropsychiatric SLE patients. Significantly higher association between migraine and aPLs was observed (n = 170/779; p 
  18. Wong KK, Lee CK, Low KS, Haron MJ
    Chemosphere, 2003 Jan;50(1):23-8.
    PMID: 12656225
    A study on the modification of rice husk by various carboxylic acids showed that tartaric acid modified rice husk (TARH) had the highest binding capacities for Cu and Pb. The carboxyl groups on the surface of the modified rice husk were primarily responsible for the sorption of metal ions. A series of batch experiments using TARH as the sorbent for the removal of Cu and Pb showed that the sorption process was pH dependent, rapid and exothermic. The sorption process conformed to the Langmuir isotherm with maximum sorption capacities of 29 and 108 mg/g at 27 +/- 2 degrees C for Cu and Pb, respectively. The uptake increased with agitation rate. Decrease in sorbent particle size led to an increase in the sorption of metal ions and this could be explained by an increase in surface area and hence binding sites. Metal uptake was reduced in the presence of competitive cations and chelators. The affinity of TARH for Pb is greater than Cu.
  19. Chua SW, Mustapha M, Wong KK, Ami M, Mohd Zahidin AZ, Nasaruddin RA
    Clin Ophthalmol, 2021;15:3147-3152.
    PMID: 34326630 DOI: 10.2147/OPTH.S320987
    Purpose: The objectives of this study were to determine the prevalence of microbial contamination of multi-user preserved ophthalmic drops (POD) in Ophthalmology Outpatient Clinic (OOC), to compare the rate of contamination between the dropper tip and the residual contents in the bottle, and to identify the contaminating organisms.

    Methods: This was an observational cross-sectional study using a convenience sampling method conducted in the OOC of Universiti Kebangsaan Malaysia Medical Center, Malaysia. The samples of POD bottles were divided into groups obtained after 14 days (T14) and after 30 days (T30) of use. The contamination rate at the dropper tip and in the residual contents was determined and the contaminating organisms were identified.

    Results: A total of 140 of 149 extended-use POD bottles were included. The prevalence of contamination was 30%. There was a statistically significant difference in the rate of contamination between samples T14 and T30 (19% and 11%, respectively; p=0.046). Proparacaine and tropicamide showed higher contamination rates in the T14 samples (p=0.027 and p=0.497, respectively) than in the T30 samples. The site of contamination was higher at the dropper tip than in the residual contents (p>0.05). Coagulase-negative Staphylococcus species were the most frequently identified contaminants (89%).

    Conclusion: The dropper tip was more contaminated than the residual contents, and coagulase-negative Staphylococcus species, which are common commensal flora of the ocular conjunctiva and skin, were the most frequently identified organisms.

  20. Wong KK
    Comput Biol Chem, 2023 Aug;105:107897.
    PMID: 37247573 DOI: 10.1016/j.compbiolchem.2023.107897
    Immunotherapy development against colorectal cancer (CRC) is hindered by the lack of cell surface target highly expressed in cancer cells but with restricted presence in normal tissues to minimize off-tumor toxicities. In this in silico analysis, a longlist of genes (n = 13,488) expressed in CRCs according to the Human Protein Atlas (HPA) database were evaluated to shortlist for potential surface targets based on the following prerequisites: (i) Absent from the brain and lung tissues to minimize the likelihood of neurologic and pulmonary toxicities; (ii) Restricted expression profile in other normal human tissues; (iii) Genes that potentially encode cell surface proteins and; (iv) At least moderately expressed in CRC cases. Fifteen potential targets were shortlisted and subsequently ranked according to the combination of their transcript and protein expression levels in CRCs derived from multiple datasets (i.e. DepMap, TCGA, CPTAC-2, and HPA CRCs). The top-ranked target with the highest and homogenous expression in CRCs was cadherin 17 (CDH17). Downstream analysis of CRC transcriptomics and proteomics datasets showed that CDH17 was significantly correlated with carcinoembryonic antigen expression. Moreover, CDH17 expression was significantly lower in CRC cases with high microsatellite instability, as well as negatively associated with immune response gene sets and the expression of MHC class I and II molecules. CDH17 represents an optimal target for therapeutic development against CRCs, and this study provides a novel framework to identify key cell surface targets for therapeutic development against other malignancies.
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