MyMedR

Displaying publications 41 - 48 of 48 in total

Abstract:

Sort:

Downregulation of CRNN gene and genomic instability at 1q21.3 in oral squamous cell carcinoma

Salahshourifar I, Vincent-Chong VK, Chang HY, Ser HL, Ramanathan A, Kallarakkal TG, et al.

Clin Oral Investig, 2015 Dec;19(9):2273-83.
PMID: 25846277 DOI: 10.1007/s00784-015-1467-7

OBJECTIVES: This study includes the direct sequencing of cornulin (CRNN) gene to elucidate the possible mechanism of CRNN downregulation and explore the genetic imbalances at 1q21.3 across oral squamous cell carcinoma (OSCC) samples.
MATERIALS AND METHODS: In mutation screening of CRNN gene, gDNA from OSCC tissues were extracted, amplified, and followed by direct sequencing. OSCC samples were also subjected to fragment analysis on CRNN gene to investigate its microsatellite instability (MSI) and loss of heterozygosity (LOH). Immunohistochemistry was performed to validate CRNN downregulation in OSCC samples.
RESULTS: No pathogenic mutation was found in CRNN gene, while high frequency of allelic imbalances was found at 1q21.3 region. MSI was found more frequent (25.3 %) than LOH (9.3 %). Approximately 22.6 % of cases had high MSI which reflects higher probability of inactivation of DNA mismatch repair genes. MSI showed significant association with no betel quid chewing (p = 0.003) and tongue subsite (p = 0.026). LOH was associated with ethnicity (p = 0.008) and advanced staging (p = 0.039). The LOH at 1q21.3 was identified to be as an independent prognostic marker in OSCC (HRR = 7.15 (95 % CI, 1.41-36.25), p = 0.018). Downregulation of CRNN was found among MSI-positive OSCCs and was associated with poor prognosis (p = 0.044).
CONCLUSION: This study showed a significant correlation between LOH/MSI at 1q21.3 with clinical outcomes and that downregulation of CRNN gene could be considered as a prognostic marker of OSCC.
CLINICAL RELEVANCE: Insights of the downregulation mode of CRNN gene lays the basis of drug development on this gene as well as revealing its prognostic value.
Survival of Oral Cancer Patients in Different Ethnicities

Ghani WMN, Ramanathan A, Prime SS, Yang YH, Razak IA, Abdul Rahman ZA, et al.

Cancer Invest, 2019;37(7):275-287.
PMID: 31307249 DOI: 10.1080/07357907.2019.1635614

Previous studies found that ethnicity influences oral cancer patients' survival; however, most studies were limited to certain ethnic groups particularly from the West, thus of limited relevance to Asians where the disease is most prevalent. We investigated the relationship between ethnicity and patient survival in multi-racial Malaysia. 5-year survival rate was 40.9%. No statistically significant difference was observed in survival between Malays, Chinese, Indians and Indigenous peoples (45.7%, 44.0%, 41.3%, 27.7% respectively). Increased tumor size, lymph node involvement and advanced tumor were predictive of poor survival. We conclude that ethnicity has no effect on survival or its prognostic indicators.
m-Health for Early Detection of Oral Cancer in Low- and Middle-Income Countries

Haron N, Zain RB, Ramanathan A, Abraham MT, Liew CS, Ng KG, et al.

Telemed J E Health, 2020 03;26(3):278-285.
PMID: 31081720 DOI: 10.1089/tmj.2018.0285

Background:
Up to 86% of oral cancer (OC) patients present at the late stage where survival is dismal. Limited access to specialist diagnosis is a significant factor for late presentation. The increasing use of smartphones presents an opportunity to use digital technology to facilitate early detection of OC.
Aim:
To evaluate the feasibility of using Mobile Mouth Screening Anywhere (MeMoSA®) to facilitate early detection of OC.
Methods:
A mobile phone app named MeMoSA was developed and the feasibility of integrating this for documentation of oral lesions, and communication between dentists and specialists for management decisions were evaluated. The experience of dentists and specialists in using MeMoSA was determined using qualitative questionnaires.
Results:
Communication between specialist and dentists using MeMoSA stratified cases and streamlined referral of patients. Twelve of 48 patients were found to have oral lesions or signs suspicious of cancer and 3 required referrals. The patient's compliance for referral was tracked with MeMoSA. All dentists agreed that MeMoSA could facilitate early detection of OC and believed that MeMoSA could assist in the identification of oral mucosal lesions through direct communication with specialists and continuous learning in the recognition of high-risk lesions.
Conclusions:
MeMoSA has the potential to be used to promote equitable health care and streamline patient management that could result in early detection of OC.
Fulltext Genome wide profiling in oral squamous cell carcinoma identifies a four genetic marker signature of prognostic significance

Vincent-Chong VK, Salahshourifar I, Woo KM, Anwar A, Razali R, Gudimella R, et al.

PLoS One, 2017;12(4):e0174865.
PMID: 28384287 DOI: 10.1371/journal.pone.0174865

BACKGROUND: Cancers of the oral cavity are primarily oral squamous cell carcinomas (OSCCs). Many of the OSCCs present at late stages with an exceptionally poor prognosis. A probable limitation in management of patients with OSCC lies in the insufficient knowledge pertaining to the linkage between copy number alterations in OSCC and oral tumourigenesis thereby resulting in an inability to deliver targeted therapy.
OBJECTIVES: The current study aimed to identify copy number alterations (CNAs) in OSCC using array comparative genomic hybridization (array CGH) and to correlate the CNAs with clinico-pathologic parameters and clinical outcomes.
MATERIALS AND METHODS: Using array CGH, genome-wide profiling was performed on 75 OSCCs. Selected genes that were harboured in the frequently amplified and deleted regions were validated using quantitative polymerase chain reaction (qPCR). Thereafter, pathway and network functional analysis were carried out using Ingenuity Pathway Analysis (IPA) software.
RESULTS: Multiple chromosomal regions including 3q, 5p, 7p, 8q, 9p, 10p, 11q were frequently amplified, while 3p and 8p chromosomal regions were frequently deleted. These findings were in confirmation with our previous study using ultra-dense array CGH. In addition, amplification of 8q, 11q, 7p and 9p and deletion of 8p chromosomal regions showed a significant correlation with clinico-pathologic parameters such as the size of the tumour, metastatic lymph nodes and pathological staging. Co-amplification of 7p, 8q, 9p and 11q regions that harbored amplified genes namely CCND1, EGFR, TPM2 and LRP12 respectively, when combined, continues to be an independent prognostic factor in OSCC.
CONCLUSION: Amplification of 3q, 5p, 7p, 8q, 9p, 10p, 11q and deletion of 3p and 8p chromosomal regions were recurrent among OSCC patients. Co-alteration of 7p, 8q, 9p and 11q was found to be associated with clinico-pathologic parameters and poor survival. These regions contain genes that play critical roles in tumourigenesis pathways.
Accelerated implementation of teleconsultation services for the monitoring of oral potentially malignant disorders as a result of the COVID-19 pandemic

Rajendran S, Mohamad Zaini Z, Lim YZ, Kallarakkal TG, Ramanathan A, Chan SW, et al.

Oral Oncol, 2022 Feb 14;126:105730.
PMID: 35176655 DOI: 10.1016/j.oraloncology.2022.105730
Fulltext Collagen Induces a More Proliferative, Migratory and Chemoresistant Phenotype in Head and Neck Cancer via DDR1

Lai SL, Tan ML, Hollows RJ, Robinson M, Ibrahim M, Margielewska S, et al.

Cancers (Basel), 2019 Nov 09;11(11).
PMID: 31717573 DOI: 10.3390/cancers11111766

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and includes squamous cell carcinomas of the oropharynx and oral cavity. Patient prognosis has remained poor for decades and molecular targeted therapies are not in routine use. Here we showed that the overall expression of collagen subunit genes was higher in cancer-associated fibroblasts (CAFs) than normal fibroblasts. Focusing on collagen8A1 and collagen11A1, we showed that collagen is produced by both CAFs and tumour cells, indicating that HNSCCs are collagen-rich environments. We then focused on discoidin domain receptor 1 (DDR1), a collagen-activated receptor tyrosine kinase, and showed that it is over-expressed in HNSCC tissues. Further, we demonstrated that collagen promoted the proliferation and migration of HNSCC cells and attenuated the apoptotic response to cisplatin. Knockdown of DDR1 in HNSCC cells demonstrated that these tumour-promoting effects of collagen are mediated by DDR1. Our data suggest that specific inhibitors of DDR1 might provide novel therapeutic opportunities to treat HNSCC.
Fulltext Genome wide analysis of chromosomal alterations in oral squamous cell carcinomas revealed over expression of MGAM and ADAM9

Vincent-Chong VK, Anwar A, Karen-Ng LP, Cheong SC, Yang YH, Pradeep PJ, et al.

PLoS One, 2013;8(2):e54705.
PMID: 23405089 DOI: 10.1371/journal.pone.0054705

Despite the advances in diagnosis and treatment of oral squamous cell carcinoma (OSCC), mortality and morbidity rates have not improved over the past decade. A major drawback in diagnosis and treatment of OSCC is the lack of knowledge relating to how genetic instability in oral cancer genomes affects oral carcinogenesis. Hence, the key aim of this study was to identify copy number alterations (CNAs) that may be cancer associated in OSCC using high-resolution array comparative genomic hybridization (aCGH). To our knowledge this is the first study to use ultra-high density aCGH microarrays to profile a large number of OSCC genomes (n = 46). The most frequently amplified CNAs were located on chromosome 11q11(52%), 2p22.3(52%), 1q21.3-q22(54%), 6p21.32(59%), 20p13(61%), 7q34(52% and 72%),8p11.23-p11.22(80%), 8q11.1-q24.4(54%), 9q13-q34.3(54%), 11q23.3-q25(57%); 14q21.3-q31.1(54%); 14q31.3-q32.33(57%), 20p13-p12.3(54%) and 20q11.21-q13.33(52%). The most frequently deleted chromosome region was located on 3q26.1 (54%). In order to verify the CNAs from aCGH using quantitative polymerase chain reaction (qPCR), the three top most amplified regions and their associated genes, namely ADAM5P (8p11.23-p11.22), MGAM (7q34) and SIRPB1 (20p13.1), were selected in this study. The ADAM5P locus was found to be amplified in 39 samples and deleted in one; MGAM (24 amplifications and 3 deletions); and SIRPB1 (12 amplifications, others undetermined). On the basis of putative cancer-related annotations, two genes, namely ADAM metallopeptidase domain 9 (ADAM9) and maltase-glucoamylase alpha-glucosidase (MGAM), that mapped to CNA regions were selected for further evaluation of their mRNA expression using reverse transcriptase qPCR. The over-expression of MGAM was confirmed with a 6.6 fold increase in expression at the mRNA level whereas the fold change in ADAM9 demonstrated a 1.6 fold increase. This study has identified significant regions in the OSCC genome that were amplified and resulted in consequent over-expression of the MGAM and ADAM9 genes that may be utilized as biological markers for OSCC.
High referral accuracy for oral cancers and oral potentially malignant disorders using telemedicine

Haron N, Rajendran S, Kallarakkal TG, Zain RB, Ramanathan A, Abraham MT, et al.

Oral Dis, 2023 Mar;29(2):380-389.
PMID: 33914993 DOI: 10.1111/odi.13892

OBJECTIVE: To evaluate the accuracy of MeMoSA®, a mobile phone application to review images of oral lesions in identifying oral cancers and oral potentially malignant disorders requiring referral.
SUBJECTS AND METHODS: A prospective study of 355 participants, including 280 with oral lesions/variants was conducted. Adults aged ≥18 treated at tertiary referral centres were included. Images of the oral cavity were taken using MeMoSA®. The identification of the presence of lesion/variant and referral decision made using MeMoSA® were compared to clinical oral examination, using kappa statistics for intra-rater agreement. Sensitivity, specificity, concordance and F1 score were computed. Images were reviewed by an off-site specialist and inter-rater agreement was evaluated. Images from sequential clinical visits were compared to evaluate observable changes in the lesions.
RESULTS: Kappa values comparing MeMoSA® with clinical oral examination in detecting a lesion and referral decision was 0.604 and 0.892, respectively. Sensitivity and specificity for referral decision were 94.0% and 95.5%. Concordance and F1 score were 94.9% and 93.3%, respectively. Inter-rater agreement for a referral decision was 0.825. Progression or regression of lesions were systematically documented using MeMoSA®.
CONCLUSION: Referral decisions made through MeMoSA® is highly comparable to clinical examination demonstrating it is a reliable telemedicine tool to facilitate the identification of high-risk lesions for early management.