MyMedR

Displaying publications 1 - 20 of 58 in total

Abstract:

Sort:

Fulltext Tissue and serum samples of patients with papillary thyroid cancer with and without benign background demonstrate different altered expression of proteins

Abdullah MI, Lee CC, Mat Junit S, Ng KL, Hashim OH

PeerJ, 2016;4:e2450.
PMID: 27672505 DOI: 10.7717/peerj.2450

Papillary thyroid cancer (PTC) is mainly diagnosed using fine-needle aspiration biopsy. This most common form of well-differentiated thyroid cancer occurs with or without a background of benign thyroid goiter (BTG).
Fulltext Papillary Thyroid Cancer: Genetic Alterations and Molecular Biomarker Investigations

Abdullah MI, Junit SM, Ng KL, Jayapalan JJ, Karikalan B, Hashim OH

Int J Med Sci, 2019;16(3):450-460.
PMID: 30911279 DOI: 10.7150/ijms.29935

Papillary thyroid cancer (PTC) is the most prevalent form of malignancy among all cancers of the thyroid. It is also one of the few cancers with a rapidly increasing incidence. PTC is usually contained within the thyroid gland and generally biologically indolent. Prognosis of the cancer is excellent, with less than 2% mortality at 5 years. However, more than 25% of patients with PTC developed a recurrence during a long term follow-up. The present article provides an updated condensed overview of PTC, which focuses mainly on the molecular alterations involved and recent biomarker investigations.
Fulltext Evaluation of steroid hormones and their receptors in development and progression of renal cell carcinoma

Bennett NC, Rajandram R, Ng KL, Gobe GC

J Kidney Cancer VHL, 2014;1(2):17-25.
PMID: 28326246 DOI: 10.15586/jkcvhl.2014.9

Steroid hormones and their receptors have important roles in normal kidney biology, and alterations in their expression and function help explain the differences in development of kidney diseases, such as nephrotic syndrome and chronic kidney disease. The distinct gender difference in incidence of renal cell carcinoma (RCC), with males having almost twice the incidence as females globally, also suggests a role for sex hormones or their receptors in RCC development and progression. There was a peak in interest in evaluating the roles of androgen and estrogen receptors in RCC pathogenesis in the late 20th century, with some positive outcomes for RCC therapy that targeted estrogen receptors, especially for metastatic disease. Since that time, however, there have been few studies that look at use of steroid hormone modulators for RCC, especially in the light of new therapies such as the tyrosine kinase inhibitors and new immune therapies, which are having some success for treatment of metastatic RCC. This review summarises past and current literature and attempts to stimulate renewed interest in research into the steroid hormones and their receptors, which might be used to effect, for example, in combination with the other newer targeted therapies for RCC.
Fulltext A diabetic lady with difficulty in breathing

Cheo SW, Ng KL, Low QJ

Malays Fam Physician, 2021 Nov 30;16(3):126-128.
PMID: 34938405 DOI: 10.51866/tyk1188
Fulltext Multifocal Primary Neoplasms in Kidney Allografts: Evaluation of Two Cases

Ellis RJ, Ng KL, Samaratunga H, Del Vecchio SJ, Wood ST, Gobe GC

J Kidney Cancer VHL, 2016;3(2):14-22.
PMID: 28326280 DOI: 10.15586/jkcvhl.2016.53

Renal cell carcinoma (RCC) is the fifth most common malignancy in kidney transplant recipients, with increased risk arising due to immunosuppression. De novo RCC occurrence in kidney allografts is much less common when compared with the native kidneys. Multifocal RCC in allograft kidneys is rarely described. In this report, we discuss two cases of de novo multifocal renal neoplasms in allograft kidneys. Case 1 had three distinct neoplastic lesions of >5 mm, and case 2 had four. Using the World Health Organization 2016 classification of adult renal tumours, case 1 had one clear-cell (cc) RCC (grade 3) and two papillary adenomas; all confined to the kidney. Case 2 had a nodular lesion classified as ccRCC (grade 4) with focal rhabdoid differentiation and some infiltration of renal sinus fat; a cc tubulopapillary RCC; a multilocular cystic renal neoplasm of low malignant potential; and a mucinous tubular and spindle cell carcinoma; the last three all confined to the kidney. This is the first report of mucinous tubular and spindle cell carcinoma in a kidney allograft. When considering multifocal RCC with discordant histology, it is likely that these represent independent tumourigenic events.
Changes in antioxidant status and DNA repair capacity are corroborated with molecular alterations in malignant thyroid tissue of patients with papillary thyroid cancer

Eng ZH, Abdul Aziz A, Ng KL, Mat Junit S

Front Mol Biosci, 2023;10:1237548.
PMID: 37692064 DOI: 10.3389/fmolb.2023.1237548

Introduction: Papillary thyroid cancer (PTC) accounts for approximately 80% of all thyroid cancer cases. The mechanism of PTC tumourigenesis is not fully understood, but oxidative imbalance is thought to play a role. To gain further insight, this study evaluated antioxidant status, DNA repair capacity and genetic alterations in individuals diagnosed with benign thyroid lesion in one lobe (BTG) and PTC lesion in another. Methods: Individuals with coexisting BTG and PTC lesions in their thyroid lobes were included in this study. Reactive oxygen species (ROS) level, ABTS radical scavenging activity, ferric reducing antioxidant capacity, glutathione peroxidase and superoxide dismutase activities were measured in the thyroid tissue lysate. The expression of selected genes and proteins associated with oxidative stress defence and DNA repair were analysed through quantitative real-time PCR and Western blotting. Molecular alterations in genomic DNA were analysed through whole-exome sequencing and the potentially pathogenic driver genes filtered through Cancer-Related Analysis of Variants Toolkit (CRAVAT) analysis were subjected to pathway enrichment analysis using Metascape. Results: Significantly higher ROS level was detected in the PTC compared to the BTG lesions. The PTC lesions had significantly higher expression of GPX1, SOD2 and OGG1 but significantly lower expression of CAT and PRDX1 genes than the BTG lesions. Pathway enrichment analysis identified "regulation of MAPK cascade," "positive regulation of ERK1 and ERK2 cascade" and "negative regulation of reactive oxygen species metabolic process" to be significantly enriched in the PTC lesions only. Four pathogenic genetic variants were identified in the PTC lesions; BRAF V600E, MAP2K7-rs2145142862, BCR-rs372013175 and CD24 NM_001291737.1:p.Gln23fs while MAP3K9 and G6PD were among 11 genes that were mutated in both BTG and PTC lesions. Conclusion: Our findings provided further insight into the connection between oxidative stress, DNA damage, and genetic changes associated with BTG-to-PTC transformation. The increased oxidative DNA damage due to the heightened ROS levels could have heralded the BTG-to-PTC transformation, potentially through mutations in the genes involved in the MAPK signalling pathway and stress-activated MAPK/JNK cascade. Further in-vitro functional analyses and studies involving a larger sample size would need to be carried out to validate the findings from this pilot study.
A mutation panel comprising BRAFV600E, NRASQ61R, and NRASQ61H replicated retrospective histopathological examination findings in differentiating benign goitre from malignant papillary thyroid cancer in a cohort of Malaysian patients

Eng ZH, Ahmad Jefry MM, Ng KL, Abdul Aziz A, Mat Junit S

Malays J Pathol, 2023 Dec;45(3):375-390.
PMID: 38155379

Thyroid malignancy status is usually confirmed through histopathological examination (HPE) following thyroidectomy. In Malaysia, the application of molecular markers in pre-operative diagnosis of thyroid cancer remains unexplored. In this study, BRAF and NRAS gene mutation panel was assessed, and the results were compared with retrospective HPE findings. Malaysian patients with benign goitre (BTG: n=33) and papillary thyroid cancer (PTC: n=25; PTCa: n=20, PTCb: n=5) were recruited at Universiti Malaya Medical Centre from September 2019 to December 2022. PCR-direct DNA sequencing of BRAFV600, NRASG12, NRASG13, and NRASQ61 was conducted on DNA extracted from the patients' thyroid tissue specimens following thyroidectomy and HPE. BRAFV600E and NRASQ61R mutations showed absolute PTC-specificity with PTC-sensitivity of 32% and 28%, respectively. NRASQ61H demonstrated lower PTC-specificity (94%) but higher PTC-sensitivity (72%) compared to the BRAFV600E and NRASQ61R mutations. Although the NRASG12 and NRASG13 variants were absent in this study, a novel NRASV14D mutation was detected in a PTCa patient. Unlike PTCb, coexistence of BRAFV600E and NRASQ61 variants was commonly observed among the PTCa patients. Notably, all PTCb patients had NRASQ61H mutation with one patient carried both the NRASQ61H and BRAFV600E mutations. Association analysis revealed potential link between gender, BRAFV600E mutation and lymph node metastasis. In conclusion, mutation panel comprising BRAFV600E, NRASQ61R, and NRASQ61H did not discriminate the two PTC subtypes but replicated the retrospective HPE findings in differentiating BTG from PTC. The application of this mutation panel in pre-operative diagnosis of thyroid nodules requires further validation in a larger sample size, preferably incorporating fineneedle aspirate biopsies.
Fulltext Whole-exome sequencing and bioinformatic analyses revealed differences in gene mutation profiles in papillary thyroid cancer patients with and without benign thyroid goitre background

Eng ZH, Abdullah MI, Ng KL, Abdul Aziz A, Arba'ie NH, Mat Rashid N, et al.

Front Endocrinol (Lausanne), 2022;13:1039494.
PMID: 36686473 DOI: 10.3389/fendo.2022.1039494

BACKGROUND: Papillary thyroid cancer (PTC) is the most common thyroid malignancy. Concurrent presence of cytomorphological benign thyroid goitre (BTG) and PTC lesion is often detected. Aberrant protein profiles were previously reported in patients with and without BTG cytomorphological background. This study aimed to evaluate gene mutation profiles to further understand the molecular mechanism underlying BTG, PTC without BTG background and PTC with BTG background.
METHODS: Patients were grouped according to the histopathological examination results: (i) BTG patients (n = 9), (ii) PTC patients without BTG background (PTCa, n = 8), and (iii) PTC patients with BTG background (PTCb, n = 5). Whole-exome sequencing (WES) was performed on genomic DNA extracted from thyroid tissue specimens. Nonsynonymous and splice-site variants with MAF of ≤ 1% in the 1000 Genomes Project were subjected to principal component analysis (PCA). PTC-specific SNVs were filtered against OncoKB and COSMIC while novel SNVs were screened through dbSNP and COSMIC databases. Functional impacts of the SNVs were predicted using PolyPhen-2 and SIFT. Protein-protein interaction (PPI) enrichment of the tumour-related genes was analysed using Metascape and MCODE algorithm.
RESULTS: PCA plots showed distinctive SNV profiles among the three groups. OncoKB and COSMIC database screening identified 36 tumour-related genes including BRCA2 and FANCD2 in all groups. BRAF and 19 additional genes were found only in PTCa and PTCb. "Pathways in cancer", "DNA repair" and "Fanconi anaemia pathway" were among the top networks shared by all groups. However, signalling pathways related to tyrosine kinases were the most significantly enriched in PTCa while "Jak-STAT signalling pathway" and "Notch signalling pathway" were the only significantly enriched in PTCb. Ten SNVs were PTC-specific of which two were novel; DCTN1 c.2786C>G (p.Ala929Gly) and TRRAP c.8735G>C (p.Ser2912Thr). Four out of the ten SNVs were unique to PTCa.
CONCLUSION: Distinctive gene mutation patterns detected in this study corroborated the previous protein profile findings. We hypothesised that the PTCa and PTCb subtypes differed in the underlying molecular mechanisms involving tyrosine kinase, Jak-STAT and Notch signalling pathways. The potential applications of the SNVs in differentiating the benign from the PTC subtypes requires further validation in a larger sample size.
Decreased apoptosis repressor with caspase recruitment domain confers resistance to sunitinib in renal cell carcinoma through alternate angiogenesis pathways

Gobe GC, Ng KL, Small DM, Vesey DA, Johnson DW, Samaratunga H, et al.

Biochem Biophys Res Commun, 2016 Apr 22;473(1):47-53.
PMID: 26995091 DOI: 10.1016/j.bbrc.2016.03.048

Apoptosis repressor with caspase recruitment domain (ARC), an endogenous inhibitor of apoptosis, is upregulated in a number of human cancers, thereby conferring drug resistance and giving a rationale for the inhibition of ARC to overcome drug resistance. Our hypothesis was that ARC would be similarly upregulated and targetable for therapy in renal cell carcinoma (RCC). Expression of ARC was assessed in 85 human RCC samples and paired non-neoplastic kidney by qPCR and immunohistochemistry, as well as in four RCC cell lines by qPCR, Western immunoblot and confocal microscopy. Contrary to expectations, ARC was significantly decreased in the majority of clear cell RCC and in three (ACHN, Caki-1 and 786-0) of the four RCC cell lines compared with the HK-2 non-cancerous human proximal tubular epithelial cell line. Inhibition of ARC with shRNA in the RCC cell line (SN12K1) that had shown increased ARC expression conferred resistance to Sunitinib, and upregulated interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). We therefore propose that decreased ARC, particularly in clear cell RCC, confers resistance to targeted therapy through restoration of tyrosine kinase-independent alternate angiogenesis pathways. Although the results are contrary to expectations from other cancer studies, they were confirmed here with multiple analytical methods. We believe the highly heterogeneous nature of cancers like RCC predicate that expression patterns of molecules must be interpreted in relation to respective matched non-neoplastic regions. In the current study, this procedure indicated that ARC is decreased in RCC.
Fulltext Randomized controlled trial comparing bilateral superficial cervical plexus block and local wound infiltration for pain control in thyroid surgery

Hoh SY, Doon YK, Chong SS, Ng KL

Asian J Surg, 2019 Dec;42(12):1001-1008.
PMID: 30857862 DOI: 10.1016/j.asjsur.2019.01.017

BACKGROUD/OBJECTIVE: Multiple approaches have been devised for pain control in patients undergoing thyroid surgery, with local wound infiltration (LWI) of analgesia and bilateral superficial cervical plexus block (BSCPB) among the popular choices cited. However, the results comparing these methods had either been contradictory or equivocal. This study was carried out to assess the efficacy of BSCPB in comparison to LWI in reducing post-operative pain, as well as any additional opioid requirement in the first 24 h after thyroid surgery.
METHODS: A prospective, double-blinded randomized controlled trial comparing the post-operative pain score between BSCPB and LWI was conducted among patients undergoing thyroid surgery. Ropivacaine 0.50% was used in the study. Pain score was measured at 4, 12, 16 and 24 h after surgery using the visual analog scale (VAS). Subcutaneous injection of Tramadol was given whenever the pain score was ≥4 or requested by patients.
RESULTS: A total of 70 patients were recruited, with 35 patients on each arm. There was no statistical difference in the post-operative pain score between the two groups at 4 h (p = 0.208), 12 h (p = 0.860), 16 h (p = 0.376) and 24 h (p = 0.375) after surgery. Time to the first rescue dose of Tramadol between the two arms was also insignificant (p = 0.949). One patient in the BSCPB arm developed transient left upper limb weakness, which resolved 12 h after surgery.
CONCLUSION: LWI remains the simplest, safest and most economical method of pain management. While BSCPB is comparable, it does however, come with potential regional block related complications.
Fulltext Interventional Pulmonology and COVID-19: Experience from a Malaysian Tertiary Hospital

Huan NC, Ng KL, Tang JT, Kua HN, Daut UN, Muhammad NA, et al.

Ann Acad Med Singap, 2020 12;49(12):1013-1017.
PMID: 33463660 DOI: 10.47102/annals-acadmedsg.2020364

The ongoing pandemic of COVID-19 has presented multiple challenges to global healthcare services, dictating changes in almost every aspect of daily medical practice. Performing aerosol generating procedures (AGPs) in the field of interventional pulmonology can lead to profound formation of aerosols, leading to a high risk of infection among healthcare workers (HCWs). We share our experiences on performing AGPs in the midst of a COVID-19 pandemic by focusing on changes in AGP practices. In a pandemic, HCWs ought to adapt to the ever-changing situation and use available resources to provide the best possible healthcare to patients, ensure safety of staff, and continue medical education of future pulmonologists.
Fulltext Conservative management of airway tear as a complication of silicone endobronchial stenting in bronchomalacia secondary to endobronchial tuberculosis

Huan NC, Ng KL, Nasaruddin MZ, Muhammad NA, Daut UN, Abdul Rahaman JA

Respirol Case Rep, 2020 Dec;8(9):e00684.
PMID: 33194207 DOI: 10.1002/rcr2.684

Tracheobronchial stenosis due to tuberculosis (TSTB) is a potentially debilitating complication of endobronchial tuberculosis (EBTB). Endobronchial interventions including silicone stent insertion is an acceptable approach to improve quality of life among patients with TSTB. However, little is known about the optimal management strategy for patients with bronchomalacia secondary to EBTB (B-EBTB) and whether stent-related complication rates are higher among this group of patients. Herein, we report two patients with B-EBTB who unfortunately developed bronchial tear related to silicone endobronchial stenting. Both patients were successfully managed conservatively without the need for emergency open surgery. We hypothesize that endobronchial intervention might be more beneficial for patients with pure TSTB and might be riskier in cases of bronchomalacia with reduced airway thickness and loss of airway cartilaginous support. More future studies are needed to bridge the current gap in knowledge regarding the optimal management and role of endobronchial interventions among patients with B-EBTB.
Fulltext Topical mitomycin-C as an adjuvant to multimodal endoscopic treatment for tracheobronchial stenosis secondary to endobronchial tuberculosis

Huan NC, Ng KL, Nasaruddin MZ, Muhammad NA, Daut UN, Abdul Rahaman JA

Respirol Case Rep, 2021 Mar;9(3):e00711.
PMID: 33532074 DOI: 10.1002/rcr2.711

Tracheobronchial stenosis secondary to endobronchial tuberculosis (TSTB) is a rare but debilitating complication of endobronchial tuberculosis (EBTB). Topical mitomycin-C (TMC) has been successfully utilized to restore airway patency and to prevent recurrence of TSTB, although little is known about its exact efficacy. Here, we report the biggest case series to date involving seven patients who received TMC as part of multimodality endoscopic treatment for TSTB with varying levels of success. All patients presented with dyspnoea during or after treatment completion for pulmonary tuberculosis (PTB). Four patients had short-segment concentric membranous TSTB while two patients had concurrent bronchomalacia. Another one patient had a thick fibrotic band adjacent to luminal opening. We hypothesize that TMC is more efficacious in short membranous stenosis without concurrent bronchomalacia and/or thick fibrotic bands. More studies are needed to bridge the current gaps in knowledge regarding the optimal role and benefits of TMC for TSTB patients.
Identification of potential complementary serum biomarkers to differentiate prostate cancer from benign prostatic hyperplasia using gel- and lectin-based proteomics analyses

Jayapalan JJ, Ng KL, Razack AH, Hashim OH

Electrophoresis, 2012 Jul;33(12):1855-62.
PMID: 22740474 DOI: 10.1002/elps.201100608

Diagnosis of prostate cancer (PCa) is currently much reliant on the invasive and time-consuming transrectal ultrasound-guided biopsy of the prostate gland, particularly in light of the inefficient use of prostate-specific antigen as its biomarker. In the present study, we have profiled the sera of patients with PCa and benign prostatic hyperplasia (BPH) using the gel- and lectin-based proteomics methods and demonstrated the significant differential expression of apolipoprotein AII, complement C3 beta chain fragment, inter-alpha-trypsin inhibitor heavy chain 4 fragment, transthyretin, alpha-1-antitrypsin, and high molecular weight kininogen (light chain) between the two groups of patients' samples. Our data are suggestive of the potential use of the serum proteins as complementary biomarkers to effectively discriminate PCa from BPH, although this requires further extensive validation on clinically representative populations.
Urine of patients with early prostate cancer contains lower levels of light chain fragments of inter-alpha-trypsin inhibitor and saposin B but increased expression of an inter-alpha-trypsin inhibitor heavy chain 4 fragment

Jayapalan JJ, Ng KL, Shuib AS, Razack AH, Hashim OH

Electrophoresis, 2013 Jun;34(11):1663-9.
PMID: 23417432 DOI: 10.1002/elps.201200583

The present study was aimed at the identification of proteins that are differentially expressed in the urine of patients with prostate cancer (PCa), those with benign prostatic hyperplasia (BPH) and age-matched healthy male control subjects. Using a combination of 2DE and MS/MS, significantly lower expression of urinary saposin B and two different fragments of inter-alpha-trypsin inhibitor light chain (ITIL) was demonstrated in the PCa patients compared to the controls. However, only one of the ITIL fragments was significantly different between the PCa and BPH patients. When image analysis was performed on urinary proteins that were transferred onto NC membranes and detected using a lectin that binds to O-glycans, a truncated fragment of inter-alpha-trypsin inhibitor heavy chain 4 was the sole protein found to be significantly enhanced in the PCa patients compared to the controls. Together, these urinary peptide fragments might be useful complementary biomarkers to indicate PCa as well as to distinguish it from BPH, although further epidemiological evidence on the specificity and sensitivity of the protein candidates is required.
iTRAQ analysis of urinary proteins: Potential use of gelsolin and osteopontin to distinguish benign thyroid goiter from papillary thyroid carcinoma

Jayapalan JJ, Lee CS, Lee CC, Ng KL, Junit SM, Hashim OH

Clin Biochem, 2018 Mar;53:127-131.
PMID: 29355489 DOI: 10.1016/j.clinbiochem.2018.01.008

BACKGROUND: Benign thyroid goiter (BTG) and papillary thyroid carcinoma (PTC) are often interchangeably misdiagnosed.
METHODS: Pooled urine samples of patients with BTG (n=10), patients with PTC (n=9) and healthy controls (n=10) were subjected to iTRAQ analysis and immunoblotting.
RESULTS: The ITRAQ analysis of the urine samples detected 646 proteins, 18 of which showed significant altered levels (p<0.01; fold-change>1.5) between patients and controls. Whilst four urinary proteins were commonly altered in both BTG and PTC patients, 14 were unique to either BTG or PTC. Amongst these, four proteins were further chosen for validation using immunoblotting, and the enhanced levels of osteopontin in BTG patients and increased levels of a truncated gelsolin fragment in PTC patients, relative to controls, appeared to corroborate the findings of the iTRAQ analysis.
CONCLUSION: The data of the present study is suggestive of the potential application of urinary osteopontin and gelsolin to discriminate patients with BTG from those with PTC non-invasively. However, this needs to be further validated in studies of individual urine samples.
Salmonella thyroid abscess-two case reports

Khoo KS, Koh PS, Ng KL

Gland Surg, 2020 Dec;9(6):2198-2203.
PMID: 33447571 DOI: 10.21037/gs-20-474

Acute suppurative thyroiditis account for <1% of thyroid diseases and is uncommon because of the gland's encapsulation, iodine-rich environment, good vascular supply and extensive lymphatic drainage. It has been reported in patients with underlying goiters, thyroid cancers and in immuno-compromised patients. The usual causative organisms are Staphylococci spp. and Streptococci spp. Rarer organisms include Klebsiella spp. and Salmonella spp. Due to its rarity (as there have been only 28 cases of Salmonella thyroid abscess being reported in the literature till 2020), only case reports are available to guide management. We report two cases of thyroid abscess due to Salmonella enteritidis in our institution that may herald the re-emergence of this uncommon infection of the thyroid gland and to raise awareness for all clinicians. Both patients presented with neck swelling, dysphagia and sepsis. Surgical intervention was warranted in both patients due to the severity of the disease and failed medical therapy. Recovery was uneventful following adequate surgical intervention and antibiotic therapy according to the culture and sensitivity report of the pathogen. This case report highlights that both patients were immunocompromised, and they contracted Salmonella thyroid abscess without any gastrointestinal involvement. Thus, a high index of suspicion for Salmonella thyroid abscess in immunocompromised patients can expedite the diagnosis and appropriate management can be commenced such as antibiotic therapy, percutaneous aspiration and surgical drainage in the event of failed medical therapy.
Fulltext Utility of pre-treatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors in breast cancer

Koh CH, Bhoo-Pathy N, Ng KL, Jabir RS, Tan GH, See MH, et al.

Br. J. Cancer, 2015 Jun 30;113(1):150-8.
PMID: 26022929 DOI: 10.1038/bjc.2015.183

Peripheral blood-derived inflammation-based scores such as the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have recently been proposed as prognostic markers in solid tumours. Although evidence to support these markers as unfavourable prognostic factors is more compelling in gastrointestinal cancers, very little is known of their impact on breast cancer. We investigated the association between the NLR and PLR, and overall survival after breast cancer.
Fulltext Functional analyses of C.2268dup in thyroid peroxidase gene associated with goitrous congenital hypothyroidism

Lee CC, Harun F, Jalaludin MY, Lim CY, Ng KL, Mat Junit S

Biomed Res Int, 2014;2014:370538.
PMID: 24745015 DOI: 10.1155/2014/370538

The c.2268dup mutation in thyroid peroxidase (TPO) gene was reported to be a founder mutation in Taiwanese patients with dyshormonogenetic congenital hypothyroidism (CH). The functional impact of the mutation is not well documented. In this study, homozygous c.2268dup mutation was detected in two Malaysian-Chinese sisters with goitrous CH. Normal and alternatively spliced TPO mRNA transcripts were present in thyroid tissues of the two sisters. The abnormal transcript contained 34 nucleotides originating from intron 12. The c.2268dup is predicted to generate a premature termination codon (PTC) at position 757 (p.Glu757X). Instead of restoring the normal reading frame, the alternatively spliced transcript has led to another stop codon at position 740 (p.Asp739ValfsX740). The two PTCs are located at 116 and 201 nucleotides upstream of the exons 13/14 junction fulfilling the requirement for a nonsense-mediated mRNA decay (NMD). Quantitative RT-PCR revealed an abundance of unidentified transcripts believed to be associated with the NMD. TPO enzyme activity was not detected in both patients, even though a faint TPO band of about 80 kD was present. In conclusion, the c.2268dup mutation leads to the formation of normal and alternatively spliced TPO mRNA transcripts with a consequential loss of TPO enzymatic activity in Malaysian-Chinese patients with goitrous CH.
Fulltext Ethnicity is an independent determinant of age-specific PSA level: findings from a multiethnic Asian setting

Lim J, Bhoo-Pathy N, Sothilingam S, Malek R, Sundram M, Hisham Bahadzor B, et al.

PLoS One, 2014;9(8):e104917.
PMID: 25111507 DOI: 10.1371/journal.pone.0104917

OBJECTIVES: To study the baseline PSA profile and determine the factors influencing the PSA levels within a multiethnic Asian setting.
MATERIALS AND METHODS: We conducted a cross-sectional study of 1054 men with no clinical evidence of prostate cancer, prostate surgery or 5α-reductase inhibitor treatment of known prostate conditions. The serum PSA concentration of each subject was assayed. Potential factors associated with PSA level including age, ethnicity, height, weight, family history of prostate cancer, lower urinary tract voiding symptoms (LUTS), prostate volume and digital rectal examination (DRE) were evaluated using univariable and multivariable analysis.
RESULTS: There were 38 men (3.6%) found to have a PSA level above 4 ng/ml and 1016 (96.4%) with a healthy PSA (≤4 ng/ml). The median PSA level of Malay, Chinese and Indian men was 1.00 ng/ml, 1.16 ng/ml and 0.83 ng/ml, respectively. Indians had a relatively lower median PSA level and prostate volume than Malays and Chinese, who shared a comparable median PSA value across all 10-years age groups. The PSA density was fairly similar amongst all ethnicities. Further analysis showed that ethnicity, weight and prostate volume were independent factors associated with age specific PSA level in the multivariable analysis (p<0.05).
CONCLUSION: These findings support the concept that the baseline PSA level varies between different ethnicities across all age groups. In addition to age and prostate volume, ethnicity may also need to be taken into account when investigating serum PSA concentrations in the multiethnic Asian population.

Filters

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links