1.The Role of ISL1 and LHX5 LIM Homeobox Genes in Bladder Tumourigenesis
Mohd Khairul Anuar Md Akhir ; Chan Soon Choy ; Maizaton Atmadini Abdullah ; Fauzah Abd Ghan ; Abhi Veerakumarasiv ; Huzlinda Hussin
Malaysian Journal of Medical Sciences 2020;27(1):37-45
Introduction: Lin-11, Isl-1 and Mec-3 domains (LIM) homeobox genes are among the most
important sub-families of homeobox genes. These genes are thought to play an important role in
cancer. In this study, the protein expression of these genes was examined in urothelial carcinoma
of the bladder. The expression pattern of Islet-1 (ISL1) and LIM homeobox 5 (LHX5) across
different cancer stages and grades, as well as the association between the protein expression of
these genes and patient demographics and clinicopathological features, were examined.
Methods: A total of 100 formalin-fixed paraffin-embedded urothelial carcinoma tissues
were selected from the Department of Pathology, Hospital Kuala Lumpur and the protein
expression of ISL1 and LHX5 was determined using immunohistochemistry.
Results: Positive expression of ISL1 and LHX5 was detected in 94% and 98% of the
samples, respectively. There were no distinct LHX5 expression patterns associated with different
cancer stages, but the proportion of high-expressing tumours was higher in high-grade tumours.
In addition, there was a significant association between the expression of LHX5 and tumour grade.
The proportion of tumours expressing high levels of ISL1 was found to be highest in later stage
tumours.
Conclusion: The high percentage of tumours expressing both these genes suggests that
ISL1 and LHX5 play an important role in bladder tumourigenesis across multiple stages.
2.Immunohistochemical expression of NANOG in urothelial carcinoma of the bladder
Mohd Khairul Anuar Md Akhir ; Huzlinda HUSSIN ; Abhimanyu VEERAKUMARASIVAM ; Chan Soon CHOY ; Maizaton Atmadini ABDULLAH ; Fauzah Abdul GHANI
The Malaysian Journal of Pathology 2017;39(3):227-234
Urothelial carcinoma is a common malignant neoplasm that has a poor prognosis and a high frequencyof recurrence and metastasis. Constant disease surveillance with periodic and long term cystoscopyexamination is necessary for management of the disease. However, the monitoring and therapyregimen is expensive, incurring a massive burden to patients and the government. Therefore, thedevelopment of specific biomarkers for urothelial carcinoma at an early stage and recurrence detectionbecomes a priority. Homeobox genes are a family of genes that are involved in tumourigenesis.They might be potential prognostic markers for urothelial carcinoma. The study investigated theexpression pattern of NANOG which is one of a homeobox gene in different stages and grades ofurothelial carcinoma. NANOG expressions were also correlated with patient demographic factors andclinicopathological parameters. The expression of NANOG in 100 formalin-fixed paraffin-embeddedurothelial carcinoma tissues was determined by immunohistochemistry. Immunohistochemistryshowed positive expression of NANOG in all specimens with detection in the cytoplasm, nucleiand the nuclear membrane of the cancer cells. The immunohistochemical expression of NANOGincreased across stages and grades of the tumour. The expression of NANOG was not significantlyassociated with demographic factors; gender (p = 0.376), race (p = 0.718) and age (p = 0.058) aswell as with most of the clinicopathological parameters; pathological stage (p = 0.144), grade (p =0.625), lymph node involvement (p = 0.174) and distant metastasis (p = 0.228). However, NANOGexpression showed significant correlation with tumour invasion (p = 0.019). We concluded thatNANOG might be a potential biomarker for early diagnosis of urothelial carcinoma of the bladder.
3.Matrix Metallopeptidase 3 Polymorphisms: Emerging genetic Markers in Human Breast Cancer Metastasis
Shafinah Ahmad SUHAIMI ; Soon Choy CHAN ; Rozita ROSLI
Journal of Breast Cancer 2020;23(1):1-9
Matrix metallopeptidase 3 or MMP3, is a zinc-dependent proteolytic enzyme that is involved in various physiological processes via modification of the extracellular matrix. In particular, its over-expression has been associated with cancer metastasis and tumor growth in various cancers including breast cancer. MMP3 gene expression is regulated by several factors such as DNA polymorphisms which also serve as risk factors for breast cancer. As such, DNA polymorphisms of MMP3 have the potential to be utilized as genetic biomarkers for prediction and prognosis of metastatic breast cancer. Presently, genome-wide association studies of MMP3 gene polymorphisms which are associated with breast cancer risk and patient survival in a variety of populations are reviewed. In order to understand the potential role of MMP3 polymorphisms as genetic markers for breast cancer metastasis, the domain structure of MMP3, the regulation of its expression and its role in breast cancer metastasis are also briefly discussed in this review. The emergence of MMP3 gene polymorphisms as prognostic biomarker candidates for breast cancer metastasis may contribute towards improving targeted therapies and categorization of breast cancer cases in order to provide a better and more accurate prognosis.
4.Multiple SNPs Downregulate Gene Expression of Matrix Metallopeptidase 2 in MCF7 Breast Cancer Cells
Shafinah Ahmad Suhaimi ; Chan Soon Choy ; Chong Pei Pei ; Chau De Ming ; Norazalina Saad ; Rozita Rosli
Malaysian Journal of Medicine and Health Sciences 2024;20(No.1):30-37
Introduction: On a global scale, breast cancer contributes the highest cancer-related deaths in women due to metastasis which renders the treatments ineffective and non-targeted. The members of Matrix Metallopeptidases, particularly Matrix Metallopeptidase 2 (MMP2), are among the key players in breast cancer metastasis. In most cases,
MMP2 was markedly upregulated and linked to poor prognosis. In a previous study, in silico analyses revealed that
several coding single nucleotide polymorphisms (SNPs) of MMP2 were shown to reduce gene expression and mRNA
stability of MMP2 in Malaysian breast cancer patients. Therefore, to validate the in silico predictions, the objective of
this study was to determine the effects of multiple coding SNPs of MMP2 on the gene expression and mRNA stability
of MMP2 in breast cancer cells. Methods: In the current study, breast adenocarcinoma MCF7 cells were transfected
with MMP2 wild type and variant containing the coding SNPs. After confirmation of transfection by DNA sequencing, the gene expression level of MMP2 was evaluated by quantitative reverse transcription polymerase chain reaction (RT-qPCR) whereas mRNA stability of MMP2 was determined following treatment with actinomycin D. Results:
MMP2 wild type and variant were successfully transfected in MCF7 cells based on sequencing and PCR analysis.
It was found that the presence of coding SNPs lowered the gene expression level of MMP2, but not the stability of
MMP2 mRNA. Conclusion: This study supports the in silico effects of MMP2 coding SNPs on its gene expression in
an in vitro model.