11thNPCRD2023

11th NASOPHARYNGEAL CARCINOMA Research Da & 13th NPCSM ANNUAL GENERAL MEETING Auditorium 2, NIH, Setia Alam 14th March 2023 9:00 a.m. - 5:00 p.m. Main-organiser: Co-organiser:

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EXECUTIVE COMMITTEE OF NASOPHARYNGEAL CARCINOMA SOCIETY OF MALAYSIA (2022-2023) President: Dr. Yap Lee Fah Vice President: Dr. Ng Ching Ching Secretary: Dr. Annie Chai Wai Yeeng Treasurer: Dr. Lim Yat Yuen (Eddie) Committee members: Ms. Norazlin Abdul Aziz Dr. Ronald Teow Sin Yeang Dr. Tan Geok Wee Auditors Ms. Low Chui Thean Dr. Susan Hoe Ling Ling ORGANISING COMMITTEE OF THE 11TH NASOPHARYNGEAL CARCINOMA RESEARCH DAY Co-chairpersons Dr. Annie Chai Wai Yeeng Dr. Tan Geok Wee Ms. Norazlin Abdul Aziz Members Dr. Susan Hoe Ling Ling Ms. Marini Marzuki Ms. Nor Soleha Mohd Dali Ms. Nurul Ashikin Mohamed Shahrehan

PROGRAMME 0800 - 0900 Registration and refreshment (Concourse, Level 5, Block D2) 0900 - 1145 Session 1 (Auditorium 2, Level 5, Block D1) 0900 – 0910 Welcoming address by the President of NPCSM 0910 - 0920 Speech by Director of IMR followed by Declaration of the Opening of 11th NPC Research Day 0920 - 1105 Moderator: Prof. Dr. Ian Paterson 0920 - 0955 Invited Talk session 0955 - 1030 1030 - 1105 Leveraging of Natural Killer Cell Therapeutics for Nasopharyngeal Carcinoma Assoc. Prof. Dr. Lim Chwee Ming, National University of Singapore Towards the Rational Design of Epstein Barr Nuclear Antigen 1 Inhibitors Dr. Xavier Chee, Swinburne University of Technology Parallel Genome-Wide RNA Interference Screens to Discover New Molecular Targets for NPC Prof. Dr. Leong Chee Onn, AGTC Genomics 1105 -1125 Sponsored Talk Next-Generation Sequencing in Liquid Biopsy: Cancer Screening and Early Detection Dr Tan Chye Ling, Chief Scientist, AGTC Genomics 1125 - 1145 Short presentations session 1 1125 - 1135 Classification of Nasopharyngeal Cases using DenseNet Deep 1135 - 1145 Learning Architecture Ms. Wan Siti Halimatul Munirah Wan Ahmad, Multimedia University Transcriptome Profiling of Nasopharyngeal Carcinoma from Patients with Different Ethnicities Ms. Chan Suat Ming, Universiti Malaya

PROGRAMME 1145 - 1245 13th NPCSM AGM (members only) 1245 - 1400 Lunch (Concourse, Level 5, Block D2) 1400 - 1700 Session 2 (Auditorium 2, Level 5, Block D1) 1400 - 1510 Moderator: Prof. Dr. Cheong Sok Ching 1400 - 1435 Invited Talk session 1435 - 1510 Integrative Multi-Omics Studies for Precision Oncology in Epstein-Barr Virus-associated Nasopharyngeal Carcinoma Dr. Wei Dai, The University of Hong Kong Multicellular Three-dimensional Tumor Spheroid as Potential in vitro Preclinical Model for Nasopharyngeal Carcinoma Research Prof. Ts Dr. Cheah Shiau Chuen, UCSI University 1510 - 1540 Short presentations session 2 1510 - 1520 Epigenetic Changes Associated with Cytotoxic T Lymphocytes 1520 - 1530 Resistance in Nasopharyngeal Carcinoma Ms. Evelyn Priya a/p Peter, Sunway University 1530 - 1540 An Oncogenic Role for EBV-encoded BILF1 in Nasopharyngeal Carcinoma Ms. Anna Wong Kang Chee, Universiti Malaya Does the Intake of Pickled Vegetables Play a Role in Affecting the Occurrence of Nasopharyngeal Carcinoma?? Dr. Aswir Abd Rashed, Institute for Medical Research 1540 - 1605 Break/judge deliberation 1605 - 1640 Invited Talk session (continued) 1605 - 1640 Extraction of Exosome from C666-1 Using Microfluidic Inertial Flow Developed in a Lab On-chip System Prof. Ts Dr. Lim Yang Mooi, Universiti Tunku Abdul Rahman 1640 - 1700 Prize giving and closing

SPEAKER PROFILE AND ABSTRACT Dr. Chwee Ming Lim Senior Consultant, Department of Otolaryngology- Head and Neck Surgery, SGH Director, Department of Clinical Translational Research Associate Professor Duke-Medical School Dr Lim graduated from the National University of Singapore and underwent residency in Otolaryngology. He pursued head and neck surgery as his subspeciality and was awarded the Ministry of Health Overseas Training award to undergo Head and Neck Oncologic Fellowship at the University of Pittsburgh Medical Centre in the United States of America. He is presently a senior consultant, head and neck surgeon at the Singapore General Hospital, Department of Otorhinolaryngology - Head & Neck Surgery. He serves as the Head of the Department of Clinical Translational Research SGH. He is also an adjunct clinician scientist at the Institute of Bioengineering and Bioimaging and an Associate Professor at the Duke-NUS Medical School. He serves as an executive board member of Asia Pacific Thyroid Society, board member of Singapore Society of Robotic Surgery and member of Asia Society of Head Neck Oncology. His research interests include cancer immunology and immunotherapy for head and neck cancers, robotic/minimally invasive surgery and real-time tissue analyses. Leveraging of NK Cell Therapeutics for NPC NK cells are innate lymphocytes responsible for eliminating virally transformed/mutated cells. In NPC, we have observed that NK cells are infiltrated into the NPC microenvironment which has prognostic significance. Additionally, with advances in cell therapy developments, generating large quantities of highly activated NK cells is feasible on a clinical scale. Using K562 as feeder cells and a cocktail of cytokines, robust expansion of NK cells can be manufactured for clinical translation. In this talk, I will discuss our team’s development of NK cells therapeutics in both refractory and advanced NPC. I will also discuss how this treatment can be integrated into the current standard of care treatment of advanced NPC.

SPEAKER PROFILE AND ABSTRACT Dr Xavier Chee Wezen Swinburne University of Technology (Sarawak Campus), Malaysia Xavier received his BSc in Chemistry (Hons) from the Department of Chemistry, Imperial College London, UK in 2014. Subsequently, he did his PhD with Dr Taufiq Rahman in the Department of Pharmacology, University of Cambridge, UK focusing on finding new antibiotics using computational drug discovery methods. After completing his PhD in 2017, Xavier decided to take break from research and went to teach Chemistry in an international school in his hometown Sibu. Later, he joined the School of Engineering & Science, Swinburne University of Technology Sarawak as a lecturer in 2019. ​His research interests include using computational drug discovery methods, molecular dynamics simulation and machine learning to find new chemicals compounds against different drug targets to treat diseases. Nowadays, his focus is on designing dual- inhibitors against various therapeutic targets. Towards the Rational Design of Epstein Barr Nuclear Antigen 1 Inhibitors Nasopharyngeal cancer (NPC) is a type of malignant tumour that is prevalent in Southern China and South East Asia. The latent infection of the Epstein Bar Virus (EBV) is a known etiological factor that leads to the development of NPC. Currently, the only known protein necessary for the maintenance of EBV episome in infected cells is the EBV Nuclear Antigen 1 (EBNA1) protein. In our work, we are interested to discover new small molecular drugs against EBNA1. Using supervised Molecular Dynamics simulation, we simulated the binding of VK-1248 (a known EBNA1 inhibitor) onto EBNA1. Combining the insights from our MD simulation and machine learning, we predicted and purchased potential EBNA1 inhibitors for experimental testing. Preliminary screening using these compounds showed differential effects against EBV-positive and EBV-negative NPC cells. Our current work continues on with gene expression studies to ascertain these compounds as bona fide EBNA1 inhibitors.

SPEAKER PROFILE AND ABSTRACT Professor Dr. Chee-Onn Leong PhD (Nottingham), Fellow (Harvard), FRSB, FRCS, FIBMS CEO, AGTC Genomics Dr. Leong has extensive experience in the field of genomics, having received several prestigious awards, including the FMD Fellowship (USA), the Institute of Biomedical Science President's Award (UK), and the Top Research Scientist Malaysia (TRSM). He was previously a Senior Research Fellow at Harvard Medical School and Massachusetts General Hospital in Boston, USA. Dr. Leong is currently a Fellow of the Institute of Biomedical Science (FIBMS, UK), Fellow of the Royal Society of Biology (FRSB, UK), and Fellow of the Royal Society of Chemistry (FRSC, UK). He served as a professor of genomics and Deputy Director of Research at the International Medical University, Malaysia. He is the founder and CEO of AGTC Genomics, a technology company that specializes in advanced genomics technology and also holds the position of adjunct professor and visiting fellow at the Broad Institute of Harvard and MIT. Parallel Genome-wide RNA Interference Screens to Discover New Molecular Targets for NPC Despite recent advancements in the treatment of nasopharyngeal carcinoma (NPC), targeted therapy remains difficult, particularly for patients with recurrent or metastatic disease. To find new targets for NPC treatment, we conducted parallel genome-wide functional screens and discovered essential genes crucial for NPC cell proliferation and cisplatin resistance. Our findings identified lymphocyte-specific protein tyrosine kinase (LCK) as a major vulnerability for both proliferation and cisplatin resistance. Depleting LCK or treating cells with LCK inhibitors caused tumor-specific cell death and improved cisplatin sensitivity in EBV-positive C666-1 and EBV-negative SUNE1 cells. Our analysis showed that LCK regulates proliferation and cisplatin resistance through the activation of signal transducer and activator of transcription 5 (STAT5). Our research provides a molecular basis for targeting LCK and STAT5 signaling as potential drug targets for NPC management.

SPEAKER PROFILE AND ABSTRACT Dr. Wei Dai (MD, MSc, PhD) Assistant Professor, Department of Clinical Oncology, The University of Hong Kong [2019-Present] Honorary Associate Professor, The University of Hong Kong Shen Zhen Hospital, China [2020-Prsent] Dr. Wei Dai is currently working as Assistant Professor in the Department of Clinical Oncology at the University of Hong Kong and honorary Associate Professor at the University of Hong Kong-Shenzhen Hospital. She obtained her PhD in Cancer Bioinformatics in the Department of Surgery and Cancer, Faculty of Medicine at Imperial College London in UK and received the Gordon Hamilton-Fairley Young Investigator Award from the British Association of Cancer Research (BACR). She was also nominated for the Outstanding Young Researcher Award in Hong Kong in 2020. With a multidisciplinary background, Dr. Dai is leading a research team including biologists, computer scientists and bioengineers working closely with clinical oncologists. Her research interest mainly lies in two areas: 1) application and development of bioinformatics tools to identify biomarkers and therapeutic targets in nasopharyngeal carcinoma (NPC) for precision medicine and 2) understanding the genetic basis and molecular mechanisms driving cancer metastasis and drug resistance by multi-omics approaches. Her studies and collaborative work have led to several papers published in PNAS, Nature Communications, Clinical Cancer Research, and eBioMedicine etc. Integrative Multi-Omics Studies for Precision Oncology in Epstein-Barr Virus-associated Nasopharyngeal Carcinoma (NPC) NPC has a distinct geographical distribution, endemic in Southeast Asia but rare worldwide. Epstein-Bar virus (EBV) is detected in over 90% of NPC cases in the endemic regions such as Hong Kong. Genome-wide association studies and epidemiology analyses suggest that genetic predisposition, environmental factors, and EBV high-risk subtypes are strong risk factors for NPC. To understand the molecular basis of NPC, we utilized the multi-omics approaches including whole-genome bisulfite sequencing (WGBS), assay for transposase-accessible chromatin using sequencing (ATAC-Seq), whole-exome sequencing (WES), bulk RNA sequencing and single-cell RNA sequencing (scRNA-Seq) data to characterize the molecular subtypes in EBV+ NPC. The genetic and epigenetic heterogeneity in EBV+ NPC was discovered by these multi-omics approaches. The results show that the APOBEC family plays an important role in orchestrating the genomic and epigenomic landscape in NPC. Moreover, we provide evidence that EBV infection is associated with reprogramming of the 2D regulatory epigenome and 3D genome architecture, leading to the EBV-specific cell communications between cancer and immune cells in the immune suppressive tumor microenvironment (TME). These findings link host factors, EBV-associated epigenetic dysregulation, TME, and immune evasion together, and highlight the importance of molecular subtyping for precision oncology in EBV+ NPC.

SPEAKER PROFILE Prof. Ts. Dr. Cheah Shiau Chuen Faculty of Medicine & Health Sciences, UCSI University, Malaysia. Prof. Ts. Dr Cheah Shiau-Chuen is a cancer biologist who have placed great interest in Cancer Biology and its precision medicine. Her interest mainly focusses on understanding the cancer physiology and targeted treatment, which include cancer stem cell in tumour microenvironment and cancer nanoparticles drug delivery. Dr Cheah has published 50 research papers in peer-reviewed journals and her Scopus H-index is 18. In her profession, she serves as a member of the European Association of Cancer Research and the American Society for Biochemistry and Molecular Biology. Dr Cheah’s interest in Nasopharyngeal carcinoma (NPC), one of the most aggressive head and neck cancers and frequently metastasises to distant lymph nodes and organs. NPC is a unique endemic to Southeast Asia, hence not adequately studied by most of the large- scale international cancer initiatives. The collective rationales hence urge the need to comprehensively investigate of the fundamental mechanism of metastatic NPC in this country. She is currently working with numerous groups of cancer scientists national and abroad, attempting to map the genomic and epigenomic landscape of nasopharyngeal carcinoma. As a cancer biologist, Dr Cheah hopes that one day in the near future she would be able to make significant contributions to the science through uncovering the targeted therapy specifically on cancer stem cell and tumour microenvironment and that the discoveries could be applied to the bedsides eventually.

ABSTRACT Multicellular Three-dimensional Tumor Spheroid as Potential in vitro Preclinical Model for Nasopharyngeal Carcinoma Research Prof. Ts. Dr. Cheah Shiau Chuen Nasopharyngeal carcinoma is one of the major public health problems in its endemic countries, especially Southern China. Metastasis and treatment resistance are the major causes of mortality in NPC. There is urgent need to develop effective therapeutic agents and biomarkers for early diagnosis through thorough understanding of the underlying pathogenesis in NPC. Although most of the NPC studies were relayed on two-dimensional model, but the tumor microenvironment involving cancer progression and metastasis are not recapitulated, hence the emergence of a more realistic three-dimensional (3D) cell culture model, that allows mimicry of physiological and pharmacological properties of in vivo human solid tumor. In present study, focus on how 3D model recapitulating in vivo TME including heterotypic cell-cell and extracellular matrix cross-talk and also provided comprehensive overview of its advantages, opportunities and applications in metastasis study, as well as its challenges in NPC cancer research. The potential of patient-derived 3D spheroid culture in heterogeneity studies and personalized medicine development was also discussed here. 3D co-culture spheroid is holding a great promise as next generation standard of in vitro pre-clinical model for biomarkers discovery, accelerating drug screening process, and achieving a more precise personalized treatment for cancer patients.

SPEAKER PROFILE Professor Ts. Dr. Lim Yang Mooi Universiti Tunku Abdul Rahman, Malaysia Professor Lim is a Professor of Biochemistry at the Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman (UTAR). She is the Deputy Director, Institute of Postgraduate Studies and Research, UTAR. She was the Founding Chairperson, and Chairperson of Centre for Cancer Research, FMHS UTAR (2011 – 2020). She was the President (2017-2021) and Immediate Past President (2021 – 2023) for the Malaysian Society for Biochemistry and Molecular Biology (MSBMB). Currently, she is the Executive Committee of the International Union for Biochemistry and Molecular Biology (IUBMB), the Chair of the Education and Training Committee, IUBMB, the Member of the Fellowship Committee of IUBMB. She was the Founding & Honorary Secretary and currently the Chair for the Organisation for Women in Science for the Developing World, Malaysia National Chapter. In March 2014, she was appointed as an accreditation panel member under the Malaysian Qualifications Agency (MQA), Ministry of Higher Education. In 2020, she was appointed as ASM Associate for Academy of Sciences Malaysia, and subsequently appointed as the member for Academy of Sciences Malaysia Publication Committee, the Session Editor for Academy of Sciences Malaysia Science Journal. In 2021, she was appointed as the Country Representative from Malaysia to the Federation of Asian Biotech Association (FABA). In April 2022, she was appointed as the member for Medical Research Ethic Committee (MREC), Ministry of Health. She received several professional certificates and fellowships such as she was elected as the Associate Fellow (2013) and Fellow (2015) for the Asean Academy of Engineering and Technology (AAET), respectively, Certificate Professional (CP) In Biorisk Management and Biosecurity from International Federation Biosafety Association (2017), Professional Technologist (BT) and Graduate Technologist from Malaysian Board of Technologist (2018), and the HRD Corp Accredited Trainer (2022) from Human Resource Development Corporation (HRD Corp). For the past 24 years, she has been greatly involved in R&D in the fields of phytochemistry, cancer chemoprevention, herbal medicine and syndrome differentiation study in Chinese Medicine, as well as the medicinal properties of edible bird’s nest. The current focused studies are to identify specific target genes that are regulated by 2- Methoxy-1,4-Naphthoquinone (MNQ) and Maslinic Acid (MA) and ultimately could be applied in precision treatment of cancer. And, to study the Traditional Chinese Medicine Zheng (Syndrome Differentiation) in understanding the mechanism of actions of Chinese herbal medicine in controlling and treating cancer from the holistic approach. Thus far, she has received numerous research grants, research awards, travel grants and fellowships nationally and internationally.

ABSTRACT Extraction of Exosome from C666-1 Using Microfluidic Inertial Flow Developed in a Lab On-chip System Boon Yew Teoh1, Yang Mooi Lim2,7, Wu Yi Chong3, Menaga Subramaniam7, Zi Zhang Tan1, Misni Misran4, Vicit Rizal Eh Suk4, Kwok-Wai Lo5, Poh Fong Lee6,* 1Department of Biomedical and Mechatronics Engineering, Lee Kong Chian Faculty of Engineering and Science, Universiti Tunku Abdul Rahman, Sungai Long Campus, Jalan Sungai Long, Kajang 43000, Cheras, Selangor, Malaysia 2Department of Pre-clinical Sciences, M. Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Sungai Long Campus, Jalan Sungai Long, Kajang 43000, Cheras, Selangor, Malaysia 3Photonics Research Centre, University of Malaya, 50603 Kuala Lumpur, Malaysia 4 Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur 5Department of Anatomical & Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong 6Department of Mechanical Engineering, Lee Kong Chian Faculty of Engineering and Science, Universiti Tunku Abdul Rahman, Sungai Long Campus, Jalan Sungai Long, Kajang 43000, Cheras, Selangor, Malaysia 7Centre for Cancer Research, Universiti Tunku Abdul Rahman, Sungai Long Campus, Jalan Sungai Long, Kajang 43000, Cheras, Selangor, Malaysia *Correspondence: [email protected]; Isolation of exosomes for cancer diagnosis is desired for a less time-consuming and cost- saving technology. In this study, an inertial microfluidic channel was developed to separate the nano-size exosome from C666-1 cell culture medium. Simulation was carried out to obtain the optimum flow rate for determining the dimension of the channels for the exosome separation. The optimal dimension was applied for the actual microfluidic channel fabrication, which consisted of the stages of mask printing, SU8 mould fabrication and ended with the PDMS microchannel curing process. The prototype was then used to verify the optimum flow rate by using polystyrene particles as a control for its capabilities in the actual task of particle separation. The microchip was then employed to separate the selected samples and exosomes from culture medium. The effectiveness of this prototype was compared with the conventional exosome extraction kit. The exosome extracted from both the prototype and extraction kits were characterised using zeta sizer, western blot and transmission electron microscopy (TEM). The microfluidic chip designed in this study obtained a successful separation of exosomes from culture medium with an evenly distributed exosome upon collection, while the exosomes separated through the extraction kit were found clustered together. This findings suggest that the microfluidic channel is suitable for the continuous separation of exosomes from the culture medium and could potentially applied in clinical study.

Short Presentation Abstract 1 Classification of Nasopharyngeal Cases using DenseNet Deep Learning Architecture Wan Siti Halimatul Munirah Wan Ahmad (PhD), Prof. Ir. Mohammad Faizal Ahmad Fauzi (PhD) Artificial Intelligence for Digital Pathology (AI4DP), Faculty of Engineering, Multimedia University, Cyberjaya, Malaysia. [email protected], [email protected] Abstract: Nasopharyngeal carcinoma (NPC) is one of the understudied and deadliest cancers in South East Asia. In Malaysia, the prevalence is identified mainly in Sarawak, among the ethnic of Bidayuh. NPC is often late-diagnosed because it is asymptomatic at the early stage. This paper is our first initiative to identify the difference between NPC, nasopharyngeal inflammation (NPI) and normal cases with the help of local pathologists from the prevalence state and capital state. Seven whole slide images (WSIs) with gigapixel resolutions from seven different patients and two hospitals were experimented using two test setups, consisting of different set of images. Image set 1 has 4 WSIs, and the diagnosed regions are in concordance with at least two pathologists. While image set 2 has 3 WSIs, with mixed regions of both concordance (NPC), and non-concordance (normal and NPI). The tissue regions from both image sets are patched into smaller blocks (256x256 pixels) and randomly chosen for training and testing of deep learning model. 5,000 patches from each class (with a total of 15,000 patches) are taken from image set 1 for training. For testing, two setups are proposed: Test 1 with 500 patches per class from image set 1 but not within the 15,000 training patches, and Test 2 with 500 patches per class taken from image set 2. The image patches are classified using DenseNet architecture with 21 dense layers, trained with only 5 epochs. The accuracy achieved for NPC class is 94.8% for Test 1 and 67.0% for Test 2. Following this preliminary experiment, more WSIs will be acquired with detailed annotations from the pathologists for further analysis to provide consistent and automated detection of NPC.

Short Presentation Abstract 2 Epigenetic Changes Associated With Cytotoxic T Lymphocytes Resistance in Nasopharyngeal Carcinoma Evelyn Priya A/P Peter1, Ling-Wei Hii2, Alan Soo-Beng Khoo3, 4, 5, Lu Ping Tan5, Chee-Onn Leong6, Tze Pheng Lau7, Cyrille Cuenin8, Zdenko Herceg8, Felicia Fei-Lei Chung1 1 Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia 2 Home Pharmacy Sdn Bhd (Alpro OPPS), 43300 Seri Kembangan, Selangor 3Center for Cancer and Stem Cell Research, Institute for Research, Development and Innovation (IRDI), and School of Postgraduate Studies, International Medical University, 57000 Kuala Lumpur, Malaysia. 4Department of Medical Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, , Philadelphia, PA 19107, United States. 5Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, 40170 Shah Alam, Selangor, Malaysia 6AGTC Genomics, Bukit Jalil, 57000 Kuala Lumpur, Malaysia 7Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia 8Epigenomics and Mechanisms Branch, International Agency for Research on Cancer (IARC), 25 avenue Tony Garnier CS 90627 69366 Lyon CEDEX 07 France Background Nasopharyngeal carcinoma (NPC) is relatively common in populations of Southern China, Southeast Asia, and certain parts of North Africa and Middle East. While studies have demonstrated that NPCs elicit an immune-suppressive tumour microenvironment that is characterized by the enrichment of exhausted T cell populations, the molecular changes that influence the susceptibility of NPC cells to T cell-mediated cytotoxicity has yet to be fully elucidated. Hence, this study aims to analyse the epigenetic changes that are associated with resistance to T cell-mediated cytotoxicity in NPC cells. Methodology Two EBV (Epstein Barr virus)-positive NPC cell lines were used for the study, namely, C666-1 and NPC43 cell lines. CD8+ T cell-resistant sublines of both cell lines were generated by repeatedly exposing parental lines to activated CD8+ T cells. The Illumina Infinium MethylationEPIC methylation array was used to identify genomic regions that are differentially methylated in resistant cell lines relative to that of the parental cell lines. The methylkey bioinformatics pipeline was used to identify differentially methylated regions (DMRs). Pathway enrichment analysis for genes associated with differentially methylated regions was carried out using Enrichr. Results Extensive differential methylation was observed in CTL-resistant sublines of NPC43 (6095 DMRs mapping to 2185 unique genes) and C666-1 (8454 DMRs mapping to 3582 unique genes) relative to their parental lines. The majority of the detected DMRs (>80%) exhibited hypermethylation relative to the parental lines. Of the detected DMRs, 597 were common between C666-1 and NPC43. Pathway enrichment analysis revealed that the common DMRs were enriched in cellular pathways associated with neuronal systems, O-linked glycosylation, and netrin-1 signalling. Conclusion Aberrant epigenetic regulation of the genomic regions identified in this study may be responsible for tumour-intrinsic resistance towards T cell-mediated cytotoxicity in NPCs. Future studies aimed at reversing these aberrations will be conducted to determine if targeted epigenetic modifications could reverse immune evasion in NPCs.

Short Presentation Abstract 3 An Oncogenic Role for EBV-encoded BILF1 in Nasopharyngeal Carcinoma A.K.C. Wong1, V. Rajendran1, W. Wei2, A. Bell3, G. Taylor3, L.S. Young4, K.W. Lo5, P.G. Murray6, I.C. Paterson1, L.F. Yap1 1 Department of Oral and Craniofacial Sciences, Faculty of Dentistry, University of Malaya, Malaysia. 2 Department of Biosciences, Durham University, Durham DH1 3LE, UK. 3 Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom. 4 Warwick Medical School, University of Warwick, Coventry CV4 7A, United Kingdom. 5 Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong. 6 Health Research Institute, University of Limerick, Ireland. Email: [email protected] It is well recognised that latent infection is the predominant mode of EBV infection in NPC in which a specific set of latent genes are key molecules in driving the development of the disease. However, the expression of these latent genes does not adequately explain the various transformed phenotypes of NPC cells. Using a high-throughput PCR array, we found that several EBV lytic genes were more widely expressed in primary NPC tissues than previously recognised. Among these, a lytic gene called BILF1 has been shown to act as a constitutively active G protein- coupled receptor and impair MHC class I functions. Re-examination of published RNAseq datasets and Q-PCR analysis showed that BILF1 was readily detectable in primary NPC tissues and cell lines. We demonstrated that conditioned media from BILF1-expressing cells inhibited the activity of EBV-specific cytotoxic T cells, pointing a role for BILF1 in immune evasion. Pathway analysis of the transcriptome of these BILF1-expressing cells showed the involvement of BILF1 in a number of key biological processes associated with carcinogenesis. Compellingly, re-analyses of published microarray datasets demonstrated that the profile of BILF1-regulated genes significantly overlapped with gene signatures of micro-dissected NPC, indicating that the expression of BILF1 is relevant to the pathogenesis of NPC. To examine whether BILF1 expression influenced epithelial cell behaviour, functional studies showed that BILF1 enhanced cell proliferation, migration and invasion, results that support the transcriptomic data. Furthermore, BILF1 enhanced AKT activation in the nasopharyngeal epithelial cells, a mechanism that is responsible for the changes in migration phenotype. Taken together, our data point to an oncogenic role for BILF1 in NPC and provide a strong foundation for investigating the functional significance of other lytic genes in this disease.

Short Presentation Abstract 4 Transcriptome Profiling of Nasopharyngeal Carcinoma from Patients with Different Ethnicities S.M. Chan1, I.P. Tang2, L.L. Tiong3, Z.M. Zaini4, I.C. Paterson1, L.F. Yap1 1Department of Oral and Craniofacial Sciences, Faculty of Dentistry, University of Malaya, Malaysia. 2Department of Otorhinolaryngology – Head and Neck Surgery, Faculty of Medicine, University Malaysia Sarawak, Malaysia. 3Clinical Research Centre (CRC) Sarawak General Hospital, Malaysia 4Department of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Malaysia. NPC is known to be predominant among Chinese populations. However, high incidences of NPC are also reported in other ethnicities, particularly the Bidayuh natives from Sarawak, who have the highest incidence of NPC in the world. To date, only a limited number of transcriptomic datasets of primary NPC are available and these data are solely obtained from Chinese patients. Using RNAseq, we comprehensively analysed the transcriptomic profiles of NPC tumours from Malaysian Bidayuh and re-examined a published RNAseq dataset on NPC from Chinese patients. Unsupervised clustering analysis showed that Bidayuh and Chinese NPCs are closely related. Focusing on differentially expressed genes between NPC and non-cancerous nasopharyngeal tissues in the respective ethnic group, we identified genes that are commonly deregulated in both ethnic groups, and genes predominantly deregulated in Bidayuh or Chinese patients. Our results showed that genes that are commonly upregulated in NPC from both ethnic groups mainly involve in extracellular structure organisation and DNA replication, while downregulated genes were enriched in immune response regulation. These data are generally in agreement with previous studies using various types of analyses, suggesting our results are valid. Significantly, we identified a number of important characteristics of Bidayuh NPC, including the involvement in type I interferon signalling pathways and translation process. Further, CIBERSORTx analysis showed that Bidayuh and Chinese NPCs exhibited different immune cell constitution in the tumour microenvironment. Taken together, our results suggest that while NPC from patients with different ethnicities possess similar key features, certain characteristics may predominate in NPC from Bidayuh patients compared to their Chinese counterparts. Such molecular features could be crucial in the development of tailored therapeutic interventions.

Short Presentation Abstract 5 Does the Intake of Pickled Vegetables Play a Role in Affecting the Occurrence of Nasopharyngeal Carcinoma? Aswir Abd Rashed and Mohammad Adi Mohammad Fadzil Nutrition Unit (NU), Nutrition, Metabolism and Cardiovascular Research Centre (NMCRC), Institute for Medical Research (IMR), National Institutes of Health (NIH), Ministry of Health Malaysia (MOH), No.1, Jalan Setia Murni U13/52, Seksyen U13 Setia Alam, Shah Alam 40170, Malaysia. Correspondence: [email protected] Background: The majority of cases of nasopharyngeal carcinoma (NPC), which is quite uncommon, are found in people from Southeast Asia and North Africa. Although the precise aetiology of NPC is unknown, it is thought to be influenced by a number of environmental and genetic variables, including exposure to certain chemicals and viruses such the Epstein-Barr virus. There is some evidence that diet and food consumption may play a role in the development of nasopharyngeal carcinoma (NPC). According to some research, consuming high amounts of salt- preserved foods, such as pickled vegetables, may increase the risk of developing NPC. Methods: The literature were extracted from three databases (PubMed, Scopus and Google Scholar) from the year 2013 to 2023 using the Medical subject heading (MeSH) terms “pickled vegetables”, crossed with the term “nasopharyngeal carcinoma \". Results: We found seventy-three related articles, however, only 5 studies were specifically focused on pickled vegetables. The findings of these research have been conflicting; whereas some have discovered a strong correlation between high consumption of pickled vegetables and the risk of NPC, while others have found no significant association. A study in Singapore has reported that those who consumed salted vegetables at least once a week showed a significantly increased risk of NPC than those who never or rarely consumed salted vegetables, with an OR of 4.18(95% CI 1.69–10.38; P = 0.002). However, a population-based case-control study conducted in Hong Kong found no significant association between pickled vegetable consumption and NPC risk, even after controlling for other potential confounders. It is unclear exactly how pickled vegetables may raise the risk of NPC, although it is thought that this is due to the high concentrations of nitrates and nitrites in these foods. Conclusion: It is important to note that the relationship between pickled vegetable consumption and NPC risk is still an area of active research, and more studies are needed to fully understand the relationship between these factors. Additionally, the role of diet in the development of NPC is complex and likely involves a combination of multiple factors, including genetic predisposition, environmental exposures, and other lifestyle factors.

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