Browsing by Author "Yang, Shun-Fa"

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A Three-MicroRNA Signature as a Potential Biomarker for the Early Detection of Oral Cancer
(2018-03-01)
Chang, Yi-An
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Weng, Shun-Long
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Yang, Shun-Fa
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Chou, Chih-Hung
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Huang, Wei-Chih
Oral squamous cell carcinoma (OSCC) is often diagnosed at a late stage and may be malignantly transformed from oral leukoplakia (OL). This study aimed to identify potential plasma microRNAs (miRNAs) for the early detection of oral cancer. Plasma from normal, OL, and OSCC patients were evaluated. Small RNA sequencing was used to screen the differently expressed miRNAs among the groups. Next, these miRNAs were validated with individual samples by quantitative real-time polymerase chain reaction (qRT-PCR) assays in the training phase (n = 72) and validation phase (n = 178). The possible physiological roles of the identified miRNAs were further investigated using bioinformatics analysis. Three miRNAs (miR-222-3p, miR-150-5p, and miR-423-5p) were identified as differentially expressed among groups; miR-222-3p and miR-423-5p negatively correlated with T stage, lymph node metastasis status, and clinical stage. A high diagnostic accuracy (Area under curve = 0.88) was demonstrated for discriminating OL from OSCC. Bioinformatics analysis reveals that miR-423-5p and miR-222-3p are significantly over-expressed in oral cancer tissues and involved in various cancer pathways. The three-plasma miRNA panel may be useful to monitor malignant progression from OL to OSCC and as potential biomarkers for early detection of oral cancer.
Bacterial alterations in salivary microbiota and their association in oral cancer
(2017-11-28)
Lee, Wei-Hsiang
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Chen, Hui-Mei
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Yang, Shun-Fa
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Liang, Chao
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Peng, Chih-Yu
Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity and the fourth leading malignancy and cause of cancer-related death in the male population of Taiwan. Most cases are detected at advanced stages, resulting in poor prognosis. Therefore, improved detection of early oral health disorders is indispensable. The involvement of oral bacteria in inflammation and their association with OSCC progression provide a feasible target for diagnosis. Due to the nature of oral neoplasms, the diagnosis of epithelial precursor lesions is relatively easy compared with that of other types of cancer. However, the transition from an epithelial precursor lesion to cancer is slow and requires further and continuous follow-up. In this study, we investigated microbiota differences between normal individuals, epithelial precursor lesion patients, and cancer patients with different lifestyle habits, such as betel chewing and smoking, using next-generation sequencing. Overall, the oral microbiome compositions of five genera, Bacillus, Enterococcus, Parvimonas, Peptostreptococcus, and Slackia, revealed significant differences between epithelial precursor lesion and cancer patients and correlated with their classification into two clusters. These composition changes might have the potential to constitute a biomarker to help in monitoring the oral carcinogenesis transition from epithelial precursor lesion to cancer.
Blepharitis as an early sign of metabolic syndrome: a nationwide population-based study
(2018-09-01)
Lee, Chia-Yi
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Chen, Hung-Chi
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Lin, Hui-Wen
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Huang, Jing-Yang
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Chao, Shih-Chun
Background To investigate the relationship between blepharitis and metabolic syndrome (MetS) by using the Longitudinal Health Insurance Database (LHID) of Taiwan. Methods This retrospective cohort study was conducted using data collected from the LHID for the period from 2009 to 2013. This study enrolled patients who received a diagnosis of blepharitis according to the International Classification of Diseases, Ninth Revision, diagnostic code. The exclusion criteria were legal blindness, eyeball removal, ocular tumours prior to the diagnosis of blepharitis, and patients diagnosed with blepharitis and initiated antibiotic treatment concurrently. An age-matched, gender-matched and disease-matched population without blepharitis served as the control group. Multivariate analysis with a multiple Cox regression model was applied to analyse the data. Results In this study, a total of 10 093 patients with blepharitis were included in the study group, and another 40 372 participants without blepharitis were included in the control group. Conditional logistic regression revealed a higher cumulative probability of hyperlipidaemia and coronary arterial disease. After adjustment, patients with blepharitis had a higher probability of developing new MetS than controls. According to subgroup analysis, hyperlipidaemia and coronary artery diseases were significantly correlated with the prior development of blepharitis. However, hypertension and diabetes mellitus and insulin resistance showed no correlation with blepharitis. Conclusion Blepharitis is significantly related to MetS and can serve as an early sign of MetS. Additional studies should examine the relationship between blepharitis and MetS in terms of severity.
Compositional and functional variations of oral microbiota associated with the mutational changes in oral cancer
(2018-02-01)
Yang, Shun-Fa
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Huang, Hsien-Da
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Fan, Wen-Lang
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Jong, Yuh-Jyh
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Chen, Mu-Kuan
Objectives: Both genetic and environmental factors are conceivably required to assess the prognosis of oral squamous cell carcinoma (OSCC), yet little is known regarding the relationship between oral microbiome and the mutational spectrum of OSCC. Materials and methods: Here, we used 16S rRNA amplicon sequencing to study the composition of oral microorganisms in OSCC patients, whose cancer mutational profiles were previously defined by whole-exome sequencing, to evaluate the relationship between oral microbiome and the mutational changes in OSCC. Results: Analyzing the contributions of the five mutational signatures extracted from the primary tumors revealed three groups of OSCC (mutational signature cluster, MSC1-3) that were significantly associated with demographic and clinical features. Taxonomic analysis of the predominant phyla in salivary samples showed variation in the relative abundance of Firmicutes and Bacteroidetes in the three MSC groups. In addition, significant differences in bacterial species richness (alpha diversity) and slight sample-to-sample dissimilarities in bacterial community structures (beta diversity) were noted among different MSC groups. Further, predicting the functional capabilities of microbial communities by reconstruction of unobserved states showed that many pathways related to cell motility were differentially enriched among the three MSC groups. Conclusion: Collectively, these results indicate a potential association of oral microbiome with the mutational changes in OSCC.
Concurrent injection of dexamethasone intravitreal implant and anti-angiogenic agent in patients with macular edema A retrospective cohort study
(2017-11-01)
Lin, Hung-Yu
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Lee, Chia-Yi
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Huang, Jing-Yang
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Yang, Shun-Fa
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Chao, Shih-Chun
To evaluate the safety and efficiency in macular edema patients who concurrently received a single injection of a dexamethasone intravitreal implant (DEX, 0.7mg) and ranibizumab (2.3 mg). A retrospective cohort study was conducted, and medical records from 2012 to 2016 were reviewed. Patients who received concurrent DEX and ranibizumab injections with a follow-up period of at least 3 months were enrolled in the study group. An age and gender-matched group received ranibizumab injections and was designated the control group. The best-corrected visual acuity (BCVA), central macular thickness (CMT) and intraocular pressure (IOP) were included in the analysis. Steroid-induced ocular hypertension (SIOH) is defined as either an elevation of more than 10 mmHg from baseline or a single IOP measurement of more than 30 mmHg. A total of 26 patients were enrolled in the current study with 13 patients in each group. Both the BCVA (P=.04) and CMT (P<.01) achieved significant improvement after the follow-up period in the study group. The IOP increased after the injection but no significant elevation was observed throughout the follow-up period in the study group (P=.15). For SIOH, 1 patient in the study group had an elevated IOP of 10 mmHg (7.7%) at 2 postoperative months, and no single IOP measurement of more than 30 mmHg was obtained. Five patients (38.5%) in the study group received medical treatment that successfully retarded their IOP elevation, and no individuals required surgical management. In the control group, there were no significant fluctuations concerning BCVA, CMT, and IOP, and no ocular hypertension was observed. According to the inter-group analysis, the CMT and BCVA recovered more significantly in the study group than in the control group. Concurrent injection of DEX and ranibizumab is a preliminary method that shows effectiveness in treating ME. Furthermore, safety is also guaranteed, with moderate levels of severity and transient IOP elevation being observed. A future large-scale study is necessary to evaluate the long-term effects and safety of this combined treatment.
Effect of Uveitis on the Development of Keratopathy: A Population-Based Cohort Study
(2018-10-01)
Nien, Chan-Wei
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Lee, Chia-Yi
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Chao, Shih-Chun
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Hsu, Hung-Jui
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Huang, Jing-Yang
PURPOSE. The purpose of this study was to evaluate the effect of uveitis on the development of various keratopathies via the use of the National Health Insurance Research Database (NHIRD) in Taiwan. METHODS. Approximately 1 million patients were randomly sampled from the registry of the NHIRD. Patients diagnosed with uveitis by ophthalmologists were enrolled in the study group after exclusion. Each individual in the study group was age and sex matched to four nonuveitis individuals who serve as the control group. In addition to keratopathy, other possible risk factors and medications were included in the multivariate model, and the effects of different subtypes of uveitis for developing keratopathies were also analyzed. RESULTS. A total of 4773 uveitis patients (2662 male and 2111 female) and 19,092 non-uveitis patients (10,648 male and 8444 female) were enrolled. There were 406 events of keratopathy in the study group, and another 764 events occurred in the control group. A higher incidence rate was found in the study group after adjustment (adjusted hazard ratio [aHR]: 1.772), with a greater cumulative probability (P < 0.0001). For the subgroup analysis, anterior uveitis (aHR = 1.765) and panuveitis (aHR = 3.386) increased the risk of developing keratopathies. Moreover, male sex was associated with a higher aHR than female sex for developing keratopathies in the study group. CONCLUSIONS. The presence of uveitis significantly elevates the risk for developing keratopathy.
Enterotype-based Analysis of Gut Microbiota along the Conventional Adenoma-Carcinoma Colorectal Cancer Pathway
(2019-07-29)
Yang, Tzu-Wei
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Lee, Wei-Hsiang
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Tu, Siang-Jyun
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Huang, Wei-Chih
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Chen, Hui-Mei
The dysbiosis of human gut microbiota is strongly associated with the development of colorectal cancer (CRC). The dysbiotic features of the transition from advanced polyp to early-stage CRC are largely unknown. We performed a 16S rRNA gene sequencing and enterotype-based gut microbiota analysis study. In addition to Bacteroides-and Prevotella-dominated enterotypes, we identified an Escherichia-dominated enterotype. We found that the dysbiotic features of CRC were dissimilar in overall samples and especially Escherichia-dominated enterotype. Besides a higher abundance of Fusobacterium, Enterococcus, and Aeromonas in all CRC faecal microbiota, we found that the most notable characteristic of CRC faecal microbiota was a decreased abundance of potential beneficial butyrate-producing bacteria. Notably, Oscillospira was depleted in the transition from advanced adenoma to stage 0 CRC, whereas Haemophilus was depleted in the transition from stage 0 to early-stage CRC. We further identified 7 different CAGs by analysing bacterial clusters. The abundance of microbiota in cluster 3 significantly increased in the CRC group, whereas that of cluster 5 decreased. The abundance of both cluster 5 and cluster 7 decreased in the Escherichia-dominated enterotype of the CRC group. We present the first enterotype-based faecal microbiota analysis. The gut microbiota of colorectal neoplasms can be influenced by its enterotype.
Overexpression of urokinase-type plasminogen activator in pterygia and pterygium fibroblasts
(2011-01-06)
Chao, Shih-Chun
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Hu, Dan-Ning
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Yang, Pei-Yu
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Lin, Ching-Yang
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Yang, Shun-Fa
Purpose: Urokinase-type plasminogen activator (uPA) is a protease involved in tissue remodeling and cell migration. Little is known about the expression of uPA in pterygium. The purpose of this study was to investigate the expression of uPA mRNA and activities in various stages of surgically excised pterygia specimens and cultured pterygium fibroblasts and to compare them with normal conjunctival tissues and fibroblasts. Methods: The expression of uPA mRNA and activity in 15 pterygium tissues and cultured fibroblasts from pterygium were measured using quantitative RT-PCR and zymography. Five normal conjunctiva specimens and cultured conjunctival fibroblasts were tested as the controls. Results: The expression of uPA mRNA and activities in pterygia and pterygium fibroblasts were significantly greater than those of the normal samples (p<0.05) and were closely related to the progression of pterygium. The amounts of uPA mRNA and activities in early, moderate, and advanced pterygia were 100%, 208%, and 311% and 100%, 157%, and 280% of the early stage specimens, respectively. The amounts of uPA mRNA and the activities in cultured pterygium fibroblasts isolated from early, moderate, and advanced pterygium specimens were 100%, 219%, and 457% and 100%, 198% and 355% of early stage fibroblasts, respectively. Conclusions: Overexpression of uPA was present in pterygium and their fibroblasts. The expression of uPA by pterygium increased significantly following the progression of the pterygium. The increased expression of uPA may covert plasminogen to plasmin, degrade extracellular matrixes, stimulate cell migration, induce angiogenesis, and plays an important role in the development and progression of pterygium.
Ultraviolet-A Irradiation Upregulated Urokinase-Type Plasminogen Activator in Pterygium Fibroblasts through ERK and JNK Pathways
(2013-02-01)
Chao, Shih-Chun
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Hu, Dan-Ning
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Yang, Pei-Yu
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Lin, Ching-Yang
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Nien, Chan-Wei
PURPOSE. Effects of ultraviolet (UV) B on the pterygium and its cells have been studied previously, whereas little is known on the effects of UVA. Urokinase-type plasminogen activator (uPA) is a protease involved in tissue remodeling and cell migration, and its levels are increased in pterygium. The purpose of our study was to investigate the effects of UVA on the expression of uPA in cultured pterygium fibroblasts. METHODS. Cultured fibroblasts from early-stage pterygia and normal conjunctiva were irradiated with different dosages of UVA and compared to nonirradiated cells. uPA activities in the medium and uPA mRNA in the cells were measured by casein zymography and RT-PCR, respectively. Total and phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular signal-related kinase (ERK), and c-Jun N-terminal kinase (JNK) levels of cells treated with and without UVA were measured by Western blotting. Inhibitors of p38 (SB203580), ERK (UO1026), and JNK (SP600125) were added before the irradiation of UVA to test their effects. RESULTS. UVA irradiation increased the uPA mRNA levels in pterygium fibroblasts and the uPA activities in cultured medium, which was accompanied with an increase in phosphorylated ERK and JNK. The ERK and JNK inhibitor, but not p38 MAPK inhibitors, significantly decreased the UVA-induced expression of uPA by pterygium fibroblasts. Normal conjunctival fibroblasts were less sensitive to UVA irradiation compared to the pterygium fibroblasts. CONCLUSIONS. UVA stimulated the production of uPA, a key factor in the modulation of extracellular matrixes, inflammatory processes, and angiogenesis. This may have a role in the development and progression of pterygium. (Invest Ophthalmol Vis Sci. 2013;54:999-1007) DOI:10.1167/iovs.12-10469
Y The Correlation of Central Serous Chorioretinopathy and Subsequent Cardiovascular Diseases of Different Types: A Population-Based Cohort Study
(2019-12-02)
Hsu, Hung-Jui
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Lee, Chia-Yi
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Chao, Shih-Chun
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Nien, Chan-Wei
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Tzeng, Shih-Hao
The aim of the present study was to survey the relationship between central serous chorioretinopathy (CSC) and several cardiovascular diseases (CVDs) with different severities using the National Health Insurance Research Database. A retrospective cohort study was conducted. Subjects with CSC were enrolled according to the relevant diagnostic codes, and an age- and gender-matched population was used as the control group with a 1:4 ratio. The main outcome being considered was the development of CVD after CSC exposure. Cox proportional hazard regression was applied to calculate the adjusted hazard ratio (aHR) of CSC and CVD of different types. A total of 2865 patients that were diagnosed with CSC were enrolled in the study group, while another 11,460 non-CSC subjects were selected as the control group. There were 171 events of CVD which occurred in the study group, while another 557 cases were found in the control group. No significant differences were observed among the CVD cases between the study and control group, whether they had an acute or chronic form, according to the aHR. In the subgroup analysis, there was a significantly higher risk of CVD development in the male population aged from 40 to 59 years (aHR: 1.351, confidence interval (CI): 1.063-1.716), which was mainly due to the higher risk of mild CVD (aHR: 1.391, CI: 1.062-1.822). On the contrary, there was no significant difference in CVD development in any of the age subgroups of the female population. In conclusion, the existence of CSC is correlated with a higher rate of chronic CVD occurrence in the middle-aged male population.