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Immunohistochemical determination of the P15 protein expression in cutaneous squamous cell carcinoma

Moad AI, Lan TM, Kaur G, Hashim H, Mabruk MJ

J Cutan Pathol, 2009 Feb;36(2):183-9.
PMID: 18564286 DOI: 10.1111/j.1600-0560.2008.00989.x

The tumor suppressor gene p15(INK4b) is a cyclin-dependent kinase inhibitor, in which its inactivation has been determined in primary tumors and in several tumor-derived cell lines. The precise role of p15(INK4b) protein expression in cutaneous squamous cell carcinoma (SCC) is currently not known. In a previous study, we have shown the frequent occurrence of allelic imbalance/loss of heterozygosity in cutaneous SCC using two microsatellite markers flanking the p15(INK4b) gene. This study is a continuation of our previous study and aims to determine the possible role of p15(INK4b) protein expression in the genesis of cutaneous SCC. P15(INK4b) protein expression was determined using immunohistochemical approach in 107 cases of cutaneous SCC tissue arrays and 19 cases of normal human skin tissues. The expression of p15(INK4b) was significantly reduced in the cutaneous SCC cases as compared with normal human skin (p = 0.017 and p < 0.05). However, there were no significant relationship between clinicopathologic variables of the patients (age, sex and tumor grade) and p15(INK4b) protein expression. The absence of p15(INK4b) expression in the majority of tissue microarray cores of cutaneous SCC indicated that p15(INK4b) could possibly be involved in the pathogenesis of cutaneous SCC.
Fulltext Immunohistochemical expression of MAP1LC3A and MAP1LC3B protein in breast carcinoma tissues

Othman EQ, Kaur G, Mutee AF, Muhammad TS, Tan ML

J Clin Lab Anal, 2009;23(4):249-58.
PMID: 19623642 DOI: 10.1002/jcla.20309

Autophagy is a protein degradation process within the cell and its deregulation has been linked to various diseases and the formation of cancer. One of the important proteins involved in the autophagy process is microtubule-associated protein 1 light chain 3 (MAP1LC3). The aims of this study were to determine the MAP1LC3A and MAP1LC3B protein expression in both normal and cancer breast tissues and to determine the relationship between the expression of these proteins and type of tissues. Immunohistochemistry assessments were carried out on tissue microarrays consisting of breast tissues. MAP1LC3A expression was detected in 52/56 of normal breast tissue cores and 65/67 of breast cancer tissue cores. MAP1LC3B expression was detected in 55/56 of normal breast tissue cores and 67/67 of breast cancer tissue cores. MAP1LC3A and MAP1LC3B protein are expressed in the majority of normal and cancer breast tissues. A large number of MAP1LC3A and MAP1LC3B positive breast cancer tissues cores have high proportion of stained cells (81-100%) as compared with normal breast tissues. However, a significantly higher number of breast cancer tissues were found to express the MAP1LC3A protein with strong immunoreactivity as compared with the normal tissues, suggesting that MAP1LC3A may play a role in breast cancer development.
Fulltext In-House Packed Porous Graphitic Carbon Columns for Liquid Chromatography-Mass Spectrometry Analysis of N-Glycans

Young C, Condina MR, Briggs MT, Moh ESX, Kaur G, Oehler MK, et al.

Front Chem, 2021;9:653959.
PMID: 34178940 DOI: 10.3389/fchem.2021.653959

Protein glycosylation is a common post-translational modification that modulates biological processes such as the immune response and protein trafficking. Altered glycosylation profiles are associated with cancer and inflammatory diseases, as well as impacting the efficacy of therapeutic monoclonal antibodies. Consisting of oligosaccharides attached to asparagine residues, enzymatically released N-linked glycans are analytically challenging due to the diversity of isomeric structures that exist. A commonly used technique for quantitative N-glycan analysis is liquid chromatography-mass spectrometry (LC-MS), which performs glycan separation and characterization. Although many reversed and normal stationary phases have been utilized for the separation of N-glycans, porous graphitic carbon (PGC) chromatography has become desirable because of its higher resolving capability, but is difficult to implement in a robust and reproducible manner. Herein, we demonstrate the analytical properties of a 15 cm fused silica capillary (75 µm i.d., 360 µm o.d.) packed in-house with Hypercarb PGC (3 µm) coupled to an Agilent 6550 Q-TOF mass spectrometer for N-glycan analysis in positive ion mode. In repeatability and intermediate precision measurements conducted on released N-glycans from a glycoprotein standard mixture, the majority of N-glycans reported low coefficients of variation with respect to retention times (≤4.2%) and peak areas (≤14.4%). N-glycans released from complex samples were also examined by PGC LC-MS. A total of 120 N-glycan structural and compositional isomers were obtained from formalin-fixed paraffin-embedded ovarian cancer tissue sections. Finally, a comparison between early- and late-stage formalin-fixed paraffin-embedded ovarian cancer tissues revealed qualitative changes in the α2,3- and α2,6-sialic acid linkage of a fucosylated bi-antennary complex N-glycan. Although the α2,3-linkage was predominant in late-stage ovarian cancer, the alternate α2,6-linkage was more prevalent in early-stage ovarian cancer. This study establishes the utility of in-house packed PGC columns for the robust and reproducible LC-MS analysis of N-glycans.
Fulltext Inhalation of honey reduces airway inflammation and histopathological changes in a rabbit model of ovalbumin-induced chronic asthma

Kamaruzaman NA, Sulaiman SA, Kaur G, Yahaya B

BMC Complement Altern Med, 2014;14:176.
PMID: 24886260 DOI: 10.1186/1472-6882-14-176

Honey is widely used in folk medicine to treat cough, fever, and inflammation. In this study, the effect of aerosolised honey on airway tissues in a rabbit model of ovalbumin (OVA)-induced asthma was investigated. The ability of honey to act either as a rescuing agent in alleviating asthma-related symptoms or as a preventive agent to preclude the occurrence of asthma was also assessed.
Inhibition of L-NAME-induced hypertension by combined treatment with apocynin and catalase: the role of Nox 4 expression

Chia TY, Murugaiyah V, Khan NA, Sattar MA, Abdulla MH, Johns EJ, et al.

Physiol Res, 2021 03 17;70(1):13-26.
PMID: 33728924

Reactive oxygen species (ROS) such as superoxide (O2-) generated by NAD(P)H oxidases have emerged as important molecules in blood pressure regulation. This study investigated the effect of apocynin and catalase on blood pressure and renal haemodynamic and excretory function in an L-NAME induced hypertension model. Forty Male Wistar-Kyoto (WKY) rats (n=8 per group) were treated with either: vehicle (WKY-C); L-NAME (WKY-L, 15 mg/kg/day in drinking fluid); WKY-L given apocynin to block NAD(P)H oxidase (WKY-LApo, 73 mg/kg/day in drinking water.); WKY-L given catalase to enhance ROS scavenging (WKY-LCat, 10000 U/kg/day i.p.); and WKY-L receiving apocynin plus catalase (WKY-LApoCat) daily for 14 days. L-NAME elevated systolic blood pressure (SBP), 116+/-1 to 181±4 mmHg, reduced creatinine clearance, 1.69+/-0.26 to 0.97+/-0.05 ml/min/kg and fractional sodium excretion, 0.84+/-0.09 to 0.55+/-0.09 % at day 14. Concomitantly, plasma malondialdehyde (MDA) increased six fold, while plasma total superoxide dismutase (T-SOD), plasma nitric oxide (NO) and plasma total antioxidant capacity (T-AOC) were decreased by 60-70 % and Nox 4 mRNA expression was increased 2-fold. Treatment with apocynin and catalase attenuated the increase in SBP and improved renal function, enhanced antioxidative stress capacity and reduced the magnitude of Nox4 mRNAs expression in the L-NAME treated rats. This study demonstrated that apocynin and catalase offset the development of L-NAME induced hypertension, renal dysfunction and reduced oxidative stress status, possibly contributed by a reduction in Nox4 expression during NOS inhibition. These findings would suggest that antioxidant compounds such as apocynin and catalase have potential in treating cardiovascular diseases.
Fulltext Key Molecular Events in Cervical Cancer Development

Balasubramaniam SD, Balakrishnan V, Oon CE, Kaur G

Medicina (Kaunas), 2019 Jul 17;55(7).
PMID: 31319555 DOI: 10.3390/medicina55070384

Cervical cancer is the fourth most common cancer among women. Infection by high-risk human papillomavirus (HPV) is the main aetiology for the development of cervical cancer. Infection by high-risk human papillomavirus (HPV) and the integration of the HPV genome into the host chromosome of cervical epithelial cells are key early events in the neoplastic progression of cervical lesions. The viral oncoproteins, mainly E6 and E7, are responsible for the initial changes in epithelial cells. The viral proteins inactivate two main tumour suppressor proteins, p53, and retinoblastoma (pRb). Inactivation of these host proteins disrupts both the DNA repair mechanisms and apoptosis, leading to rapid cell proliferation. Multiple genes involved in DNA repair, cell proliferation, growth factor activity, angiogenesis, as well as mitogenesis genes become highly expressed in cervical intraepithelial neoplasia (CIN) and cancer. This genomic instability encourages HPV-infected cells to progress towards invasive carcinoma. The key molecular events involved in cervical carcinogenesis will be discussed in this review.
Lack of increased P15INK4B protein expression in basal cell carcinomas

Moad AI, Tan ML, Kaur G, Mabruk M

Asian Pac J Cancer Prev, 2012;13(12):6239-44.
PMID: 23464438

BACKGROUND: The basal cell carcinoma (BCC) is the most common non-melanoma skin cancer (NMSK). BCC might develop because of the faulty cell cycle arrest. P15INK4b is a tumor suppressor gene, involved in cell cycle arrest and inactivated in most human cancers. The role of p15INK4b protein expression in the genesis of BCC is as yet unknown. In a previous study we showed the absence of p15INK4b expression in the majority of tissue microarray cores of cutaneous squamous cell carcinoma (SCCs), another type of non-melanoma skin cancer, indicating that p15INK4b could possibly be involved in the pathogenesis of cutaneous SCC. The aim of this study was to investigate p15INK4b protein expression in BCCs.
MATERIALS AND METHOD: Protein expression of p15INK4b in 35 cases of BCC tissue arrays and 19 cases of normal human skin tissue was studied using an immunohistochemical approach.
RESULTS: The expression of p15INK4b was not significantly different in the BCC cases as compared with normal human skin (p=0.356; p>0.05). In addition, there were no significant relationship between clinicopathologic variables of patients (age and sex) and p15INK4b protein expression.
CONCLUSIONS: Our finding may indicate that p15INK4b protein expression does not play a role in the genesis of BCC.
Lymph node metastasis of primary endometrial cancers: Associated proteins revealed by MALDI imaging

Mittal P, Klingler-Hoffmann M, Arentz G, Winderbaum L, Lokman NA, Zhang C, et al.

Proteomics, 2016 06;16(11-12):1793-801.
PMID: 27061135 DOI: 10.1002/pmic.201500455

Metastasis is a crucial step of malignant progression and is the primary cause of death from endometrial cancer. However, clinicians presently face the challenge that conventional surgical-pathological variables, such as tumour size, depth of myometrial invasion, histological grade, lymphovascular space invasion or radiological imaging are unable to predict with accuracy if the primary tumour has metastasized. In the current retrospective study, we have used primary tumour samples of endometrial cancer patients diagnosed with (n = 16) and without (n = 27) lymph node metastasis to identify potential discriminators. Using peptide matrix assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI), we have identified m/z values which can classify 88% of all tumours correctly. The top discriminative m/z values were identified using a combination of in situ sequencing and LC-MS/MS from digested tumour samples. Two of the proteins identified, plectin and α-Actin-2, were used for validation studies using LC-MS/MS data independent analysis (DIA) and immunohistochemistry. In summary, MALDI-MSI has the potential to identify discriminators of metastasis using primary tumour samples.
MALDI Mass Spectrometry Imaging of Early- and Late-Stage Serous Ovarian Cancer Tissue Reveals Stage-Specific N-Glycans

Briggs MT, Condina MR, Ho YY, Everest-Dass AV, Mittal P, Kaur G, et al.

Proteomics, 2019 11;19(21-22):e1800482.
PMID: 31364262 DOI: 10.1002/pmic.201800482

Epithelial ovarian cancer is one of the most fatal gynecological malignancies in adult women. As studies on protein N-glycosylation have extensively reported aberrant patterns in the ovarian cancer tumor microenvironment, obtaining spatial information will uncover tumor-specific N-glycan alterations in ovarian cancer development and progression. matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is employed to investigate N-glycan distribution on formalin-fixed paraffin-embedded ovarian cancer tissue sections from early- and late-stage patients. Tumor-specific N-glycans are identified and structurally characterized by porous graphitized carbon-liquid chromatography-electrospray ionization-tandem mass spectrometry (PGC-LC-ESI-MS/MS), and then assigned to high-resolution images obtained from MALDI-MSI. Spatial distribution of 14 N-glycans is obtained by MALDI-MSI and 42 N-glycans (including structural and compositional isomers) identified and structurally characterized by LC-MS. The spatial distribution of oligomannose, complex neutral, bisecting, and sialylated N-glycan families are localized to the tumor regions of late-stage ovarian cancer patients relative to early-stage patients. Potential N-glycan diagnostic markers that emerge include the oligomannose structure, (Hex)6 + (Man)3 (GlcNAc)2 , and the complex neutral structure, (Hex)2 (HexNAc)2 (Deoxyhexose)1 + (Man)3 (GlcNAc)2 . The distribution of these markers is evaluated using a tissue microarray of early- and late-stage patients.
Maggot debridement therapy to treat hard-to-heal diabetic foot ulcers: a single-centre study

Nair HK, Ahmad NW, Ismail AA, Alabed AAA, Zheming BO, Kaur G, et al.

J Wound Care, 2021 12 01;30(Sup12):S30-S36.
PMID: 34882006 DOI: 10.12968/jowc.2021.30.Sup12.S30

OBJECTIVE: Maggot debridement therapy (MDT) has seen a resurgence in recent years in the treatment of hard-to-heal wounds, as a result of rising antibiotic resistance. The sterilised larvae of Lucilia cuprina have been used in MDT in Malaysia since 2003, with encouraging results for the treatment of hard-to-heal diabetic wounds. We report a case series of 30 patients selected from our clinic by convenient sampling with diabetic lower limb ulcers treated with MDT. The average age of patients receiving MDT was >50 years. Of the 30 patients in the study, nine were female and 21 were male. All patients had underlying diabetes, two patients had leg ulcers and 28 patients had diabetic foot ulcers. Sterilised Lucilia cuprina larvae were applied via a standard method of 10 maggots per square centimetre and dressed with sterile gauze. The study endpoint was defined as ≤5% coverage with slough or necrotic tissue following three successive applications of MDT. In this study, maximum debridement of wounds was achieved in 96.6% (29 patients) of our patients, with ≤5% coverage with slough or necrotic tissue, in addition to a reduction in wound-related pain, as assessed by a visual analogue scale. No adverse events were reported. The findings of this study support the use of MDT as a safe, efficacious, and cost-effective method of managing diabetic wounds.
Metastatic mucinous carcinoma of the eyelid

Kaur G, Ismail R, Harun H

Malays J Pathol, 2005 Dec;27(2):117-8.
PMID: 17191395

Metastatic eyelid tumours are rare and account for less than 2% of all eyelid neoplasms. We report a case of metastatic breast carcinoma to the eyelid in a 60-year-old Chinese lady presenting with a 2-year history of enlarging, painless nodular lower eyelid swelling. The 1 cm diameter lesion was provisionally diagnosed as a sebaceous cyst. However the excision biopsy revealed a mucinous carcinoma expressing oestrogen receptor protein. She had a past history of mastectomy one year previously and histology showed an infiltrating ductal carcinoma (oestrogen receptor status negative) without evidence of axillary lymph node metastasis. She had completed adjuvant radio- and chemotherapy. Further treatment of the current lesion involved a wide excision which did not show any residual malignancy. She had no other evidence of metastasis and was treated with letrozol. We highlight this case to create awareness among clinicians and opthalmologists on the possibility of metastatic disease as a cause of eyelid swelling, especially in patients with a history of cancer. It may also be the first sign of metastatic disease of an internal malignancy. A review of the literature is also presented.
Fulltext Minichromosome Maintenance Complex (MCM) Genes Profiling and MCM2 Protein Expression in Cervical Cancer Development

Kaur G, Balasubramaniam SD, Lee YJ, Balakrishnan V, Oon CE

Asian Pac J Cancer Prev, 2019 Oct 01;20(10):3043-3049.
PMID: 31653153 DOI: 10.31557/APJCP.2019.20.10.3043

OBJECTIVE: Minichromosome maintenance complex (MCM) proteins are essential for the process of DNA replication and cell division. This study aimed to evaluate MCM genes expression profiles and MCM2 protein in HPV-associated cervical carcinogenesis.
METHODOLOGY: MCM2, 4, 5 and 7 genes expression profiles were evaluated in three cervical tissue samples each of normal cervix, human papillomavirus (HPV)-infected low grade squamous intraepithelial lesion (LSIL), high grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC), using Human Transcriptome Array 2.0 and validated by nCounter® PanCancer Pathway NanoString Array. Immunohistochemical expression of MCM2 protein was semi-quantitatively assessed by histoscore in tissue microarrays containing 9 cases of normal cervix, 10 LSIL, 10 HSIL and 42 cases of SCC.
RESULTS: MCM2, 4, 5 and 7 genes expressions were upregulated with increasing fold change during the progression from LSIL to HSIL and the highest in SCC. MCM2 gene had the highest fold change in SCC compared to normal cervix. Immunohistochemically, MCM2 protein was localised in the nuclei of basal cells of normal cervical epithelium and dysplastic-neoplastic cells of CIN and SCC. There was a significant difference in MCM2 protein expression between the histological groups (P = 0.039), and histoscore was the highest in HSIL compared to normal cervix (P = 0.010).
CONCLUSION: The upregulation of MCM genes expressions in cervical carcinogenesis reaffirms MCM as a proliferative marker in DNA replication pathway, whereby proliferation of dysplastic and cancer cells become increasingly dysregulated and uncontrolled. A strong expression of MCM2 protein in HSIL may aid as a concatenated screening tool in detecting pre-cancerous cervical lesions.
Mismatch repair genes expression defects & association with clinicopathological characteristics in colorectal carcinoma

Kaur G, Masoud A, Raihan N, Radzi M, Khamizar W, Kam LS

Indian J Med Res, 2011 Aug;134:186-92.
PMID: 21911971

DNA mismatch repair gene (MMR) abnormalities are seen in 95 per cent of hereditary nonpolyposis colorectal cancer (HNPCC) and 10-15 per cent of sporadic colorectal cancers. There are no data on MMR abnormalities in Malaysian colorectal cancer patients. This study was aimed to determine the frequency of abnormal MMR gene protein expression in colorectal carcinoma in Northern Peninsular Malaysia using immunohistochemistry.
Fulltext Mucinous adenocarcinoma of the renal pelvis associated with lithiasis and chronic gout

Kaur G, Naik VR, Rahman MNG

Singapore Med J, 2004 Mar;45(3):125-6.
PMID: 15029415

Diffusely-infiltrating mucinous adenocarcinoma of the renal pelvis associated with lithiasis and chronic gout is reported in a 61-year-old Malay man. The patient underwent left nephrectomy and vesiculo-lithotomy. This tumour is postulated to arise in response to chronic irritation of the urothelium.
Myxoid liposarcoma of the breast in a 25-year-old female as a diagnostic pitfall in fine needle aspiration cytology: report of a rare case

Pant I, Kaur G, Joshi SC, Khalid IA

Diagn Cytopathol, 2008 Sep;36(9):674-7.
PMID: 18677756 DOI: 10.1002/dc.20913

Primary sarcomas of the breast are extremely rare comprising less than 1.0% of all malignant tumors of the breast. It is even rarer to be reported in a 25-year-old female. This can cause a diagnostic dilemma not only for the clinician but also for the cytopathologist. A 25-year-old woman presented with a well defined firm, mobile lump in her right breast. With fine needle aspiration cytology (FNAC) and ultrasonography a diagnosis of fibroadenoma was made. The patient underwent lumpectomy. Histopathologically it was diagnosed as myxoid liposarcoma. This case is reported to highlight the fact that, even though rare in young females but the possibility of a breast lump being a myxoid liposarcoma does exist. This report discusses a primary myxoid liposarcoma of female breast, considers cytologic differential diagnoses with review of the relevant literature.
N-Glycan matrix-assisted laser desorption/ionization mass spectrometry imaging protocol for formalin-fixed paraffin-embedded tissues

Briggs MT, Ho YY, Kaur G, Oehler MK, Everest-Dass AV, Packer NH, et al.

Rapid Commun Mass Spectrom, 2017 May 30;31(10):825-841.
PMID: 28271569 DOI: 10.1002/rcm.7845

RATIONALE: Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of the proteome of a tissue has been an established technique for the past decade. In the last few years, MALDI-MSI of the N-glycome has emerged as a novel MALDI-MSI technique. To assess the accuracy and clinical significance of the N-linked glycan spatial distribution, we have developed a method that utilises MALDI-MSI followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) in order to assign glycan structures to the differentiating MALDI-MSI glycan masses released from the tissue glycoproteins.
METHODS AND RESULTS: Our workflow presents a comprehensive list of instructions on how to (i) apply MALDI-MSI to spatially map the N-glycome across formalin-fixed paraffin-embedded (FFPE) clinical samples, (ii) structurally characterise N-glycans extracted from consecutive FFPE tissue sections by LC/MS/MS, and (iii) match relevant N-glycan masses from MALDI-MSI with confirmed N-glycan structures determined by LC/MS/MS.
CONCLUSIONS: Our protocol provides groups that are new to this technique with instructions how to establish N-glycan MALDI-MSI in their laboratory. Furthermore, the method assigns N-glycan structural detail to the masses obtained in the MALDI-MS image. Copyright © 2017 John Wiley & Sons, Ltd.
Fulltext N-glycan MALDI Imaging Mass Spectrometry on Formalin-Fixed Paraffin-Embedded Tissue Enables the Delineation of Ovarian Cancer Tissues

Everest-Dass AV, Briggs MT, Kaur G, Oehler MK, Hoffmann P, Packer NH

Mol Cell Proteomics, 2016 09;15(9):3003-16.
PMID: 27412689 DOI: 10.1074/mcp.M116.059816

Ovarian cancer is a fatal gynaecological malignancy in adult women with a five-year overall survival rate of only 30%. Glycomic and glycoproteomic profiling studies have reported extensive protein glycosylation pattern alterations in ovarian cancer. Therefore, spatio-temporal investigation of these glycosylation changes may unearth tissue-specific changes that occur in the development and progression of ovarian cancer. A novel method for investigating tissue-specific N-linked glycans is using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) on formalin-fixed paraffin-embedded (FFPE) tissue sections that can spatially profile N-glycan compositions released from proteins in tissue-specific regions. In this study, tissue regions of interest (e.g. tumor, stroma, adipose tissue and necrotic areas) were isolated from FFPE tissue sections of advanced serous ovarian cancers (n = 3). PGC-LC-ESI-MS/MS and MALDI-MSI were used as complementary techniques to firstly generate structural information on the tissue-specific glycans in order to then obtain high resolution images of the glycan structure distribution in ovarian cancer tissue. The N-linked glycan repertoires carried by the proteins in these tissue regions were structurally characterized for the first time in FFPE ovarian cancer tissue regions, using enzymatic peptide-N-glycosidase F (PNGase F) release of N-glycans. The released glycans were analyzed by porous graphitized carbon liquid chromatography (PGC-LC) and collision induced electrospray negative mode MS fragmentation analysis. The N-glycan profiles identified by this analysis were then used to determine the location and distribution of each N-glycan on FFPE ovarian cancer sections that were treated with PNGase F using high resolution MALDI-MSI. A tissue-specific distribution of N-glycan structures identified particular regions of the ovarian cancer sections. For example, high mannose glycans were predominantly expressed in the tumor tissue region whereas complex/hybrid N-glycans were significantly abundant in the intervening stroma. Therefore, tumor and non-tumor tissue regions were clearly demarcated solely on their N-glycan structure distributions.
Fulltext Nasopharyngeal Carcinoma (NPC) Risk Factors: A Systematic Review and Meta-Analysis of the Association with Lifestyle, Diets, Socioeconomic and Sociodemographic in Asian Region

Okekpa SI, S M N Mydin RB, Mangantig E, Azmi NSA, Zahari SNS, Kaur G, et al.

Asian Pac J Cancer Prev, 2019 Nov 01;20(11):3505-3514.
PMID: 31759378 DOI: 10.31557/APJCP.2019.20.11.3505

OBJECTIVE: Risk factors of nasopharyngeal carcinoma (NPC) have been linked with diets, life style and viral
infections. NPC is more rampant in Asian populations than non-Asian countries. Our study aims to assess the validity
of the suggestions provided by multiple case control studies demonstrating that salted fish consumption, smoking and
alcohol consumption are associated with the risk of NPC in Asia.
METHODS: Search for related literature on salted fish,
smoking and alcohol consumption were performed via Science Direct, PubMed databases and Google Scholar. Articles
included in this study were from 2009 to 2017, with specific focus on salted fish, smoking and alcohol consumption
as risk factors of NPC. This study excluded all articles published prior to 2009 and articles involving other cancers.
Data were extracted independently by two different researchers and harmonized. Meta-analysis was conducted on the
obtained data, by using R package Meta to create funnel and forest plots.
RESULTS: The meta-analysis revealed that
salted fish, smoking and alcohol consumption were significantly associated to NPC risk with random effect model score
showing OR of 1.41 at 95% confidence interval (CI) of 1.13-1.75 (P<0.01), OR of 1.89 at 95 % CI of 1.49 - 2.38, and
OR: 1.42 at 95 % CI of 1.23 - 1.65 respectively. Our results also revealed significant association of salted meat, salted
vegetables, house type, wood dust exposure associated with NPC risk with p values less than 0.05.
CONCLUSION: This
study proposes that salted fish intake, smoking and alcohol consumption might be linked to NPC risk in Asians. Further
studies are necessary to ascertain the molecular mechanisms and clarify if the associated path that could function as
therapeutic target.
Novel IEF Peptide Fractionation Method Reveals a Detailed Profile of N-Terminal Acetylation in Chemotherapy-Responsive and -Resistant Ovarian Cancer Cells

Weiland F, Arentz G, Klingler-Hoffmann M, McCarthy P, Lokman NA, Kaur G, et al.

J Proteome Res, 2016 11 04;15(11):4073-4081.
PMID: 27569743

Although acetylation is regarded as a common protein modification, a detailed proteome-wide profile of this post-translational modification may reveal important biological insight regarding differential acetylation of individual proteins. Here we optimized a novel peptide IEF fractionation method for use prior to LC-MS/MS analysis to obtain a more in depth coverage of N-terminally acetylated proteins from complex samples. Application of the method to the analysis of the serous ovarian cancer cell line OVCAR-5 identified 344 N-terminally acetylated proteins, 12 of which are previously unreported. The protein peptidyl-prolyl cis-trans isomerase A (PPIA) was detected in both the N-terminally acetylated and unmodified forms and was further analyzed by data-independent acquisition in carboplatin-responsive parental OVCAR-5 cells and carboplatin-resistant OVCAR-5 cells. This revealed a higher ratio of unacetylated to acetylated N-terminal PPIA in the parental compared with the carboplatin-resistant OVCAR-5 cells and a 4.1-fold increase in PPIA abundance overall in the parental cells relative to carboplatin-resistant OVCAR-5 cells (P = 0.015). In summary, the novel IEF peptide fractionation method presented here is robust, reproducible, and can be applied to the profiling of N-terminally acetylated proteins. All mass spectrometry data is available as a ProteomeXchange repository (PXD003547).
Nuclear and stromal expression of Manic fringe in renal cell carcinoma

Cheng WK, Kaur G, Sjöberg E, Frödin M, Egevad L, Harmenberg U, et al.

Exp Mol Pathol, 2021 Aug 08;122:104667.
PMID: 34371013 DOI: 10.1016/j.yexmp.2021.104667

Renal cell carcinoma (RCC) is the most common type of kidney cancer and has the highest mortality rate among genitourinary cancers. Despite the advances in molecular targeted therapies to treat RCC, the inevitable emergence of resistance has delineated the need to uncover biomarkers to prospectively identify patient response to treatment and more accurately predict patient prognosis. Fringe is a fucose specific β1, 3N-acetylglucosaminyltransferase that modifies the Notch receptors. Given the link between its function and aberrant Notch activation in RCC, Fringe may be implicated in this disease. The Fringe homologs comprise of Lunatic fringe (LFng), Manic fringe (MFng) and Radical fringe (RFng). MFng has been reported to play a role in cancer. MFng is also essential in the development of B cells. However, the expression profile and clinical significance of MFng, and its association with B cells in RCC are unknown. CD20 is a clinically employed biomarker for B cells. This pilot study aimed to determine if MFng protein expression can be utilized as a prospective biomarker for therapeutics and prognosis in RCC, as well as to determine its association with CD20+ B cells. Analysis of publicly available MFng gene expression datasets on The Cancer Genome Atlas Netlwork (TCGA) identified MFng gene expression to be up-regulated in Kidney Clear Cell Renal Carcinoma (KIRC) patients. However there was no significant association between the patient survival probability and the level of MFng expression in this cohort. Immunohistochemistry performed on a tissue microarray containing cores from 64 patients revealed an elevated MFng protein expression in the epithelial and stromal tissues of RCC compared to the normal kidney, suggesting a possible role in tumorigenesis. Our study describes for the first time to our knowledge, the protein expression of MFng in the nuclear compartment of normal kidney and RCC, implicating a prospective involvement in gene transcription. At the cellular level, cytoplasmic MFng was also abundant in the normal kidney and RCC. However, MFng protein expression in the malignant epithelial and stromal tissue of RCC had no positive correlation with the patients' overall survival, progression-free survival and time to metastasis, as well as the gender, age, tumor stage and RCC subtype, indicating that MFng may not be an appropriate prognostic marker. The association between CD20+ B cells and epithelial MFng was found to approach borderline insignificance. Nonetheless, these preliminary findings may provide valuable information on the suitability of MFng as a potential therapeutic molecular marker for RCC, thus warrants further investigation using a larger cohort.

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