Hypermethylation of genes on chromosome 3p as a biomarker for nasopharyngeal carcinoma diagnosis: A Vietnamese case-control study.

BACKGROUND: The crucial event driving nasopharyngeal tumorigenesis is the hypermethylation of chromosome 3p-located tumor suppressor genes. This case-control study aims to investigate the methylation characteristics of RASSF1A, Blu, ADAMTS9, and DLEC1 to potentially develop effective diagnostic biomarkers for nasopharyngeal carcinoma, either individually or in combination. METHODS: The methylation of RASSF1A, Blu, ADAMTS9, and DLEC1 in the collection of 93 biopsy samples and 100 healthy swab specimens were evaluated by Nested methylation-specific polymerase chain reaction. The strength of the correlation between candidate genes and nasopharyngeal carcinoma was estimated by the evaluation of odds ratios (ORs). RESULTS: Promoter hypermethylation of RASSF1A, Blu, ADAMTS9, and DLEC1 were found in 60.22%, 80.65%, 62.37%, and 74.19%, respectively, in nasopharyngeal carcinoma tumors. A significant association between the methylation status of candidate genes with nasopharyngeal carcinoma was reported. The methylation of candidate genes significantly increased the risk of nasopharyngeal carcinoma in cancerous samples compared with control samples (OR > 1). Based on the value of the methylation index, methylation of at least one gene was found in 95.70% of nasopharyngeal tumors. Additionally, the methylation index among 93 tumors significantly correlated with advanced stage nasopharyngeal tumors. CONCLUSION: The study explored a higher frequency of hypermethylation at least one candidate gene. Methylation of a panel of potential genes can be utilized to discriminate between nasopharyngeal carcinoma and non-cancer cells, particularly in the advanced stages of nasopharyngeal carcinoma. Thus, it could serve as a valuable marker for the diagnosis and monitoring of nasopharyngeal carcinoma.

Insights into Sucrose Metabolism and Its Ethylene-Dependent Regulation in Cucumis melo L.

The melon (Cucumis melo L.), a fruit crop of significant economic importance, is prized for its sweet and succulent fruits. Among variations of soluble sugars, sucrose, a disaccharide composed of glucose and fructose, is a key carbohydrate present in melon fruits. The sucrose content also determines the quality and value of melon fruits. However, the accumulation of sucrose is a complex process involving the coordinated actions of multiple enzymes and pathways. In melon species, there are two types of fruit ripening modes including climacteric and non-climacteric. Due to this biological characteristic, melon is emerging as a good model for studying the ripening process. Ethylene is a well-known phytohormone regulating the ripening of climacteric fruits. Recently, a few studies have elucidated a primary ethylene-dependent signaling pathway of sucrose accumulation in melon fruits. This review aims to provide a careful overview of the sucrose biosynthesis pathways in melon. It is essential to understand the molecular mechanisms of sucrose metabolism as well as its regulation mode. The information will be useful for developing molecular marker-assisted breeding as well as genetic engineering strategies aiming to improve the sucrose content and quality of melon fruits. In addition, even though limited, the impacts of genetic background and environmental factors on sucrose accumulation in melon fruits are also discussed. These are useful for practical applications in melon cultivation and quality management.

Diagnostic Value of DAPK Methylation for Nasopharyngeal Carcinoma: Meta-Analysis.

BACKGROUND: Methylation of DAPK has been reported to play a key role in the initiation and progression of nasopharyngeal cancer. However, there are differences between the studies on it. This meta-analysis was performed to evaluate the diagnostic value of DAPK promoter methylation for NPC. METHOD: The study method involves the systematic research of eligible studies based on criteria. The frequency, odds ratios (OR), sensitivity as well as specificity with the corresponding 95% confidence intervals (CIs) were used to assess the effect sizes. RESULTS: A total of 13 studies, including 1048 NPC samples and 446 non-cancerous samples, were used for the meta-analysis. The overall frequencies of DAPK methylation were 56.94% and 9.28% in NPC samples and non-cancerous samples, respectively. The association between DAPK methylation and risk of NPC was also confirmed by calculating the OR value which was 13.13 (95%CI = 54.24-40.72) based on a random-effect model (Q = 64.74; p < 0.0001; I2 = 81.47% with 95%CI for I2 = 69.39-88.78). Additionally, the study results suggest that testing for DAPK methylation in tissue samples or brushing may provide a promising method for diagnosing NPC. CONCLUSION: This is the first meta-analysis that provided scientific evidence that methylation of the DAPK gene could serve as a potential biomarker for diagnosis, prognosis, and early screening of NPC patients.

Hybridization Between the Canary Melon and a Vietnamese Non-sweet Melon Cultivar Aiming to Improve the Growth Performance and Fruit Quality in Melon (Cucumis melo L.).

Canary melon has been widely consumed as a dessert fruit due to its fragrance, sweetness, and flavorful taste. However, the cultivation of this cultivar has been challenged in Vietnam because of its weak growth performance and high susceptibility to local pathogens. In this study, we aim to generate the hybrid melon lines between the Canary melon and a local non-sweet melon that are expected to produce good quality fruits as well as to show better growth performance in the local cultivation conditions. Two crossing pairs including (1) MS hybrid (♂ non-sweet melon × â™€ Canary melon) and (2) MN-S hybrid (♂ Canary melon × â™€ non-sweet melon) were carried out and two hybrid lines were subsequently obtained. Next, different phenotypic and physiological parameters such as stem length, stem diameter, 10th leaf diameter, fruit size, fruit weight, and fruit sweetness (pH, °Brix, and soluble sugar contents) were examined and compared between the parental lines (Canary melon and non-sweet melon) and the hybrid lines (MS and MN-S). The results showed that the stem length and fruit size and weight of MS and MN-S hybrids were higher than those of Canary melon. Basically, the content of sugars (sucrose, glucose, and fructose) is a primary and important factor in determining the sweetness of the melon. The pH, °Brix, sucrose and glucose contents of MS hybrid and Canary melon fruits were higher in comparison to MN-S and non-sweet melon fruits. Accordingly, the transcript levels of different sugar metabolism-related genes including SUCROSE SYNTHASE 1 (SUS1), SUS2, UDPGLC EPIMERASE 3 (UGE3), and SUCROSE-P SYNTHASE 2 (SPS2) were examined in all studied lines. In the fruits, the expression levels of these genes were found to be highest in the Canary melon, average in the MS hybrid, and relatively low in the MN-S hybrid and non-sweet melons. Taken together, the heterosis in terms of plant and fruit size was obviously observed in this crossing approach. The relatively high fruit sweetness in the MS hybrid (the mother is Canary melon) also implies that the choice of the mother for crossing is very important since it can determine the fruit quality of the offspring.

Circulating microRNAs as the Potential Diagnostic and Prognostic Biomarkers for Nasopharyngeal Carcinoma.

microRNAs are endogenous non-coding miRNAs, 19-25 nucleotides in length, that can be detected in the extracellular environment in stable forms, named circulating miRNAs (CIR-miRNAs). Since the first discovery of CIR-miRNAs, a large number of studies have demonstrated that the abnormal changes in its expression could be used to significantly distinguish nasopharyngeal carcinoma (NPC) from healthy cells. We herein reviewed and highlighted recent advances in the study of CIR-miRNAs in NPC, which pointed out the main components serving as promising and effective biomarkers for NPC diagnosis and prognosis. Furthermore, brief descriptions of its origin and unique characteristics are provided.

Hypermethylation of the RASSF1A gene promoter as the tumor DNA marker for nasopharyngeal carcinoma.

BACKGROUND: RASSF1A is a tumor suppressor gene. The methylation of RASSF1A has been reported to be associated with nasopharyngeal tumorigenesis. However, the heterogeneity was high among different studies. A meta-analysis was performed to evaluate the value of RASSF1A methylation for the diagnosis and early screening of nasopharyngeal carcinoma. METHODS: Relevant articles were identified by searching the MEDLINE database. Frequency and odds ratio (OR) were applied to estimate the effect of CDH-1 methylation based on random-/fixed-effect models. The meta-analysis was performed by using MedCalc® software. Subgroup analyses were performed by test method, ethnicity, and source of nasopharyngeal carcinoma samples to determine likely sources of heterogeneity. RESULTS: A total of 17 studies, including 1688 samples (1165 nasopharyngeal carcinoma samples, and 523 from non-cancerous samples) were used for the meta-analysis. The overall frequencies of RASSF1A methylation were 59.68% and 2.65% in case-group and control-group, respectively. By removing the poor relative studies, the heterogeneity was not observed among the studies included. The association between RASSF1A gene methylation and the risk of nasopharyngeal carcinoma was also confirmed by calculating the OR value of 30.32 (95%CI = 18.22-50.47) in the fixed-effect model (Q = 16.41, p = 0.36,I2 = 8.62, 95% CI = 0.00-45.27). Additionally, the significant association was also found between the methylation of the RASSF1A gene and the subgroups. CONCLUSIONS: This is the first meta-analysis that has provided scientific evidence that the methylation of RASSF1A is the potential diagnosis, prognosis, and early screening biomarker for nasopharyngeal carcinoma.

Upregulation of miRNA-155 in Nasopharyngeal Carcinoma Patients.

BACKGROUND: The upregulation of miRNA-155 (miR-155) has been associated with oncogenesis of many human tumors, including nasopharyngeal carcinoma (NPC). However, the profile of miR-155 in Vietnamese NPC patients has not been investigated. The current study aimed to evaluate the miR-155 expression and assess whether miR-155 is a potential biomarker for diagnosis of NPC in Vietnamese patients. METHODS: In current case-control study, total of RNA was isolated from 60 biopsy NPC samples and 60 non-cancerous swab samples were analyzed by Reverse-transcription PCR, qualitative Real-time PCR. RESULTS: The frequency of miR-155 detection were 78.33%, 15.0% in NPC and non-cancerous samples (P<0.05), respectively. The miR-155 expression level was 4.92 times higher in tumor samples than non-cancerous sample. CONCLUSION: Taken together, miR-155 in NPC was upregulated. It may serve as a potential biomarker for NPC in the Vietnamese population.

The Role of hsa-miR-21 and Its Target Genes Involved in Nasopharyngeal Carcinoma.

OBJECTIVE: MicroRNAs (miRNAs) are key post-transcriptional regulators of protein translation in humans. They have an essential role in various cancers, including nasopharyngeal carcinoma (NPC). The abnormal expression of miR-21 has been proven to be associated with various types of cancers, including NPC, through its targets. This study provides a systematic view of the roles of miR-21 and its network of targets (hsa-miR-21-3p, hsa-miR-21-5p) that are associated with nasopharyngeal carcinoma. METHODS: Bioinformatics tools were applied to predict the targets of miR-21. Interactions among the targets of hsa-miR-21-3p/5p were found by the gene MANIA online tool. RESULTS AND CONCLUSION: It was found that the target genes are involved in vital biological processes in cancer. In detail, a total of 95 targets of miR-21 were recorded to be associated with NPC. Therefore, they may provide new insights into nasopharyngeal pathogenesis and bring about novel targets for NPC diagnosis as well as therapy in near future.

Promoter Hypermethylation of Tumor Suppressor Genes Located on Short Arm of the Chromosome 3 as Potential Biomarker for the Diagnosis of Nasopharyngeal Carcinoma.

DNA methylation, the most common epigenetic alteration, has been proven to play important roles in nasopharyngeal carcinoma (NPC). Numerous tumor suppressor genes located on the chromosome 3p, particularly in the region of 3p21, are frequently methylated in NPC, thus suggesting great potential for diagnosis of NPC. In this review, we summarize recent findings of tumor suppressor genes on chromosome 3 that likely drive nasopharyngeal tumor development and progression, based on previous studies related to the hypermethylation of these target genes. Better understanding will allow us to design further experiments to establish a potential test for diagnosis of NPC, as well as bring about methylated therapies to improve the treatment of NPC.

Data Integration Reveals the Potential Biomarkers of Circulating MicroRNAs in Osteoarthritis.

The abnormal expression of circulating miRNAs (c-miRNAs) has become an emerging field in the development of miRNAs-based diagnostic and therapeutic tools for human diseases, including osteoarthritis (OA). OA is the most common form of arthritis leading to disability and a major socioeconomic burden. The abnormal expression of miRNAs plays important roles in the pathogenesis of OA. Unraveling the role of miRNAs in the pathogenesis of OA will throw light on the potential for the development of miRNAs-based diagnostic and therapeutic tools for OA. This article reviews and highlights recent advances in the study of miRNAs in OA, with specific demonstration of the functions of miRNA, especially c-miRNA, in OA pathogenesis as well as its potential implication in the treatment of OA. Based on a systematic literature search using online databases, we figured out the following main points: (1) the integrative systematic review of c-mRNAs and its target genes related to OA pathogenesis; (2) the potential use of c-miRNAs for OA diagnosis purposes as potential biomarkers; and (3) for therapeutic purposes, and we also highlight certain remedies that regulate microRNA expression based on its target genes.

Morphological and genetic characteristics of the novel entomopathogenic fungus Ophiocordyceps langbianensis (Ophiocordycipitaceae, Hypocreales) from Lang Biang Biosphere Reserve, Vietnam.

An entomopathogenic fungus newly named Ophiocordyceps langbianensis was collected from Lang Biang Biosphere Reserve, located in Lam Dong Province, Vietnam. It is characterized as a species of Ophiocordyceps (Ophiocordycipitaceae, Hypocreales) having the unique characteristics of a cylindrical fertile part and several branched apical appendices. Each ascospore develops as two swollen, constricted part-spores. A phylogenetic analysis of multiple genes, including nrLSU, nrSSU, Rpb1, ITS and Tef, supported its systematic position in the genus of Ophiocordyceps; it is related to O. brunneipunctata. Based on morphological and phylogenetic analyses, O. langbianensis was confirmed as a new species from Vietnam.

Association Between LMP-1, LMP-2, and miR-155 Expression as Potential Biomarker in Nasopharyngeal Carcinoma Patients: A Case/Control Study in Vietnam.

Background: Epstein-Barr virus (EBV) infection and microRNA-155 (miR-155) are considered etiological factors that contribute to nasopharyngeal carcinoma (NPC). The regulation of miR-155 expression induced by EBV infection has been reported to be important in NPC tumorigenesis. Aims: This study was designed to explore the relationships among the expression levels of miR-155, LMP-1 (latent membrane protein-1), and LMP-2 (latent membrane protein-2) in tumor and nontumor specimens of Vietnamese NPC patients. The study was also designed to investigate the association between miR-155 expression and LMP-1 and LMP-2 expression in Vietnamese NPC patients. Materials and Methods: Ninety-three NPC biopsy samples and 100 noncancerous swab specimens were collected from patients and analyzed by real-time reverse transcriptase polymerase chain reaction. Results: LMP-1, LMP2, and miR-155 were significantly upregulated in 76.34%, 67.74%, and 75.27% of NPC samples, respectively, with decreased expression observed in the control group (p < 0.0001). Moreover, the statistical analysis showed that there was a close association between LMP-1 and LMP-2 expression and miR-155 expression in the NPC samples. Conclusion: miR-155 expression was upregulated and significantly associated with the expression of LMP-1 and LMP-2, in Vietnamese NPC cases.

Molecular Screening of Nasopharyngeal Carcinoma: Detection of LMP-1, LMP-2 Gene Expression in Vietnamese Nasopharyngeal Swab Samples.

Objective: This study aimed to characterize the expression of LMP-1, LMP-2 in clinical swab samples in order to find out the potential molecular based biomarker for NPC diagnosis and screening, which could offer a chance in development of rapid method for NPC diagnosis in Vietnamese population. Materials and Methods: A total of 93 nasopharyngeal carcinoma swab samples and 100 healthy nasopharyngeal swab samples were collected to evaluate LMP-1, LMP-2 expression by Real-time reversed PCR. Results: we figured out the significant association between the expression of LMP-1 (counting for 48.39%), LMP-2 (counting for 39.78%) and NPC. No LMP-1 expression was observed, and only 1 of 100 specimens was detected with LMP-2 positive in healthy samples. In the combination of LMP-1 (+) and/or LMP-2 (+), the frequency of positive was 53.76%, greater than each gene expression. Additionally, sensitivity, specificity, positive predictive value, negative predictive value of assay were 99.00%, 98.04%, 69.72%, and 77.02%, respectively. Additionally, the LMP-2 expression level was 5.50 times higher in NPC samples than non-cancerous samples. Conclusion: Our results indicated the molecular invasive method based on the expression of LMP-1, LMP-2 in swab samples would be a promising supplement in NPC diagnosis, screening in the near future in Vietnam.

Hypermethylation of DcR1 Gene-based Biomarker in Non-invasive Cancer Screening of Vietnamese Cervical Cancer Patients.

BACKGROUND: The infection of human papillomavirus (HPV) has been considered as the common cause of cervical cancer, which is the leading cause of cancer death in women, in Vietnam. Recently, hypermethylation at tumor suppressor genes (TSGs) has been also demonstrated to be an early epigenetic event and cofactor in human cancer, including cancer of cervix. This study evaluated the frequency of DcR1 gene promoter hyper-methylation status as well as whether did or not an association between patterns of DNA hypermethylation and high-risk HPV infection, led to risk of cervical cancer. METHODS: Methylation-Specific-PCR (MSP) was performed to analyze hypermethylation status from 109 liquid-based Papanicolaou test samples, archived and admitted from the Medic Medical Center and Au Lac Clinic Laboratory, Vietnam, from 2011-2014, a kind of non-invasive samples identified whether HPV/or non-HPV, high-risk/low-risk HPV infection. RESULTS: DcR1 promoter was differentially methylated in 50% cases of high-risk HPV genotype 16 and 18 infected samples. In contrast, a low frequency of hypermethylated DcR1 promoter was found in low risk HPV genotype infected sample (16.0%), and non-HPV infected sample (14.6%). A trend toward positive association was found between hypermethylation of DcR1 gene and HPV exposure was observed (P=0.0005). Moreover, the odds ratio (OR) and relative risk (RR) were found in statistical significant value (OR=5.63 (95%CI = 2.25 - 14.07, P<0.01), RR=3.31 (95%CI = 1.75 - 6.26, P<0.01)). CONCLUSION: The hypermethylation of DcR1 gene promoter is a significant characteristic of high-risk HPV infected samples in Vietnamese cervical patients. The OR and RR values showed that the strong correlation between DcR1 hypermethylation and high-risk HPV infection, in which increased the risk of cervical cancer. The combination of DcR1 hypermethylation and HPV detection based biomarker could be used in noninvasive samples obtained from high-risk cancer patients, offer significant practical advantages.

Evaluation of p16INK4α Hypermethylation from Liquid-based Pap Test Samples in Vietnamese Population.

BACKGROUND: Human papillomavirus (HPV) infection has been considered as main cause of cervical cancer. Recently, aberrant DNA methylation at tumor suppressor genes (TSGs), leading to inactivation, has also been an early epigenetic event and cofactor in cervical carcinogenesis. This study was performed to evaluate an association between the hypermethylation of p16INK4α gene's promoter and HPV exposure in non-invasive samples (liquid-based papanicolaous samples) in Vietnamese population. METHODS: 109 liquid-based papanicolaous test samples were archived and admitted from the Medic Medical Center and Au Lac Clinic Laboratory, Vietnam, from 2011-2014. Methylation-Specific-PCR (MSP) was performed to analyze methylation status from the liquid-based papanicolaous test samples identified whether HPV/or non-HPV, high-risk/low-risk HPV infection. RESULTS: An upward trend was observed concerning the p16INK4α hypermethylation frequency in high-risk HPV infection, counting for 55.6%, and the low methylation frequency in low-risk and non-HPV infected samples, counting for 22.9%, 8.0%, respectively. The significant correlation between candidate p16INK4α hypermethylation and HPV exposure was observed (P<0.0001). Moreover, the odds ratio (OR) and relative risk (RR) were found in statistical significant value. (OR=5.76, 95%CI: 2.36 - 14.04, P<0.01; RR=3.11, 95%CI: 1.75-5.53, P<0.01). CONCLUSION: Presence of p16INK4α hypermethylation was the specific characteristic of high-risk HPV infected samples in Vietnamese population. The OR and RR values showed that the strong correlation between p16INK4α hypermethylation and high-risk HPV infection, in which increased the risk of cervical cancer. The combination of p16INK4α hyper-methylation and HPV detection based biomarker could be used in non-invasive samples obtained from high-risk cancer patients, offer significant practical advantages.

Molecular Screening for Epstein-Barr virus (EBV): Detection of Genomic EBNA-1, EBNA-2, LMP-1, LMP-2 Among Vietnamese Patients with Nasopharyngeal Brush Samples

Epstein-Bar virus (EBV) is considered to be intimately associated with development of nasopharyngeal carcinoma (NPC), the most common and high incidence cancer of the head and neck in Asian countries, especially in Vietnam. In this study, we validated associations between highly conserved segments of the EBV genome, including EBNA-1, EBNA-2, LMP-1, LMP-2 and nasopharyngeal cancer, with the aim of applications with non-invasive brush samples for early diagnosis and as a prognostic biomarker. The polymerase chain reaction (PCR) was performed to assess the presence of EBNA-1, EBNA-2, LMP-1, LMP-2 in nasopharyngeal brush samples from Vietnamese NPC patients and non-cancer controls. Positive rates for EBNA-1, EBNA-2, LMP-1, LMP-2 were 46.3%, 49.5% and 45.3%, and 47.4%, respectively, in cancer cases, much higher than the low frequencies found in non-cancer samples. Notably, at least one of the four (PI ≥ 0.25) was found in 57. 9%. Significance was reached when computing the odds ratio (OR) and relative risk (RR). Our detection of candidate genes. in nasopharyngeal brush samples collected from Vietnamese patients reduces the need for invasive biopsies and fulfills the characteristics of a non-invasive, specific screening method suitable for routine, NPC risk assessment for EBV-infected populations. Notably, this procedure may be useful for confirmatory screening with large oral brush swabs.

Loss of expression of cyclin d2 by aberrant DNA methylation: a potential biomarker in vietnamese breast cancer patients.

DNA methylation of tumor suppressor gene promoters is the most frequent phenomenon leading to inactivation of function, consequently driving malignant cell transformation. Cyclin D2 is implicated in tumor suppression. In our study, we carried out the MSP assay to evaluation the methylation status at CpG islands in the cyclin D2 promoter in breast cancer cases from the Vietnamese population. The results showed that the frequency of methylation reached 62.1% (59 of 95 breast cancer tumors), but was low in non-cancer specimens at 10% (2 of 20 non-cancer specimens). Additionally, with an RR (relative risk) and OR (odd ratios) of 6.21 and 14.8, DNA hypermethylation of cyclin D2 increased the possibility of malignant transformation. Our results confirmed the cyclin D2 hypermethylation could be used as the potential biomarker which could be applied in prognosis and early diagnosis of Vietnamese breast cancer patients.

BRCA1 promoter hypermethylation signature for early detection of breast cancer in the Vietnamese population.

Breast cancer, a leading cause of death among women in most countries worldwide, is rapidly increasing in incidence in Vietnam. One of biomarkers is the disruption of the genetic material including epigenetic changes like DNA methylation. With the aim of finding hypermethylation at CpG islands of promoter of BRCA1 gene, belonged to the tumor suppressor gene family, as the biomarker for breast cancer in Vietnamese population, sensitive methyl specific PCR (MSP) was carried out on 115 samples including 95 breast cancer specimens and 20 normal breast tissues with other diseases which were obtained from Ho Chi Minh City Medical Hospital, Vietnam. The result indicated that the frequency of BRCA1 hypermethylation reached 82.1% in the cases (p<0.001). In addition, the DNA hypermethylation of this candidate gene increased the possibility to be breast cancer with high incidence via calculated odd ratios (p<0.05). In conclusion, hypermethylation of this candidate gene could be used as the promising biomarker application with Vietnamese breast cancer patients.