Integrated analysis of fine-needle-aspiration cystic fluid proteome, cancer cell secretome, and public transcriptome datasets for papillary thyroid cancer biomarker discovery.

Thyroid ultrasound and ultrasound-guided fine-needle aspiration (USG/FNA) biopsy are currently used for diagnosing papillary thyroid carcinoma (PTC), but their detection limit could be improved by combining other biomarkers. To discover novel PTC biomarkers, we herein applied a GeLC-MS/MS strategy to analyze the proteome profiles of serum-abundant-protein-depleted FNA cystic fluid from benign and PTC patients, as well as two PTC cell line secretomes. From them, we identified 346, 488, and 2105 proteins, respectively. Comparative analysis revealed that 191 proteins were detected in the PTC but not the benign cystic fluid samples, and thus may represent potential PTC biomarkers. Among these proteins, 101 were detected in the PTC cell line secretomes, and seven of them (NPC2, CTSC, AGRN, GPNMB, DPP4, ERAP2, and SH3BGRL3) were reported in public PTC transcriptome datasets as having 4681 elevated mRNA expression in PTC. Immunoblot analysis confirmed the elevated expression levels of five proteins (NPC2, CTSC, GPNMB, DPP4, and ERAP2) in PTC versus benign cystic fluids. Immunohistochemical studies from near 100 pairs of PTC tissue and their adjacent non-tumor counterparts further showed that AGRN (n = 98), CTSC (n = 99), ERAP2 (n = 98) and GPNMB (n = 100) were significantly (p < 0.05) overexpressed in PTC and higher expression levels of AGRN and CTSC were also significantly associated with metastasis and poor prognosis of PTC patients. Collectively, our results indicate that an integrated analysis of FNA cystic fluid proteome, cancer cell secretome and tissue transcriptome datasets represents a useful strategy for efficiently discovering novel PTC biomarker candidates.

Incidences of cancers in diabetic and non-diabetic hospitalized adult patients in Taiwan.

BACKGROUND: The study was to investigate the relationship between diabetes mellitus ( DM), specific cancers, age, and gender. METHODS: This was a retrospective study that examined the frequency of different forms of cancer among male and female patients with or without DM admitted to a single hospital in Taiwan between January 2009 and June 2010. RESULTS: Of 101,002 study patients admitted to the hospital, 15,901 (15.74%) were diagnosed with DM and 16,748 (16.58%) with a malignancy. The frequency of DM differed between males and females (17.5% vs 14.2%; P<0.001), and males had a higher cancer incidence than females (20.2% vs 13.5%; P<0.001). Patients with DM had a greater frequency of cancer diagnosis than non-DM patients (18.1% vs 16.3%, respectively), with pancreatic, liver, uterine, urinary tract, lung, and secondary cancers being more frequent in DM compared with non-DM patients. In contrast, the proportion of patients with thyroid, esophagus, breast, NPC, and other cancers was lower in DM versus non-DM patients. CONCLUSIONS: This study found that DM was associated with the incidence of specific cancers and that males had a higher frequency of cancer than females. The association of DM and cancer depended upon cancer type, gender, and age.

Acute aortic dissection presenting as case of accidental falling with flaccidity of left lower extremity.

Aortic dissection is often a catastrophic, life-threatening condition that may not always present with symptoms. Without intensive treatment, the mortality within the first 2 weeks of onset is reportedly as high as 80%. Acute aortic dissection classically presents with the symptoms of abrupt chest pain that sometimes radiates to the back, abdominal pain, or back pain alone. The patient may be cool and clammy, which is indicative of a shock syndrome. It can be associated with neurologic sequelae in as many as one third of all patients. Painless dissection occurs in approximately 5% of patients, and the diagnosis may often be delayed. We report a case of aortic dissection where the patient presented with a history of accidental fall and a new onset of flaccidity of the left lower limb.

Serum uric acid and leptin levels in metabolic syndrome: a quandary over the role of uric acid.

This study investigates the impact of uric acid (UA) on the risk factors associated with metabolic syndrome. In addition, this study explores the relationship between UA and insulin resistance and serum leptin levels in metabolic syndrome. A total of 470 subjects (252 women and 218 men) were recruited from the Department of Health Management at Chang Gung Medical Center (Linkou, Taiwan). Metabolic syndrome was defined using a modified Adult Treatment Panel III (ATP III) definition. The formula for the homeostasis model assessment of insulin resistance (HOMA-IR) is as follows: fasting serum insulin (microU/mL) x fasting plasma glucose (mmol/L)/22.5. Diabetes mellitus was diagnosed in 45 subjects (9.6%); 82 subjects (17.4%) had hypertension. Hyperuricemia was diagnosed in 144 subjects (30.6%). Of these subjects, 115 (63 females and 52 males) (24.5%) were diagnosed as having metabolic syndrome. Patients with hyperuricemia had increased body mass index, waist-to-hip ratio, and triglyceride (Tg) level. The subjects also had lower high-density lipoprotein and greater hypertension. Hormone assays showed an elevation of leptin, immunoreactive insulin (IRI), and HOMA-IR in the hyperuricemia group. Uric acid appeared to be better correlated with Tg, blood pressure (both systolic and diastolic), obesity, immunoreactive insulin, and HOMA-IR. Uric acid did not correlate with leptin or blood glucose levels. Metabolic syndrome and Tg/high-density lipoprotein ratio showed a statistically significant difference in HOMA-IR using 3.8 as a cutoff value. Otherwise, there was no difference in leptin value. In conclusion, serum UA is significantly related to risk factors of metabolic syndrome except for blood glucose. Waist-to-hip ratio and HOMA-IR were statistically different in subjects with and without metabolic syndrome.

An aberrant autocrine activation of the platelet-derived growth factor alpha-receptor in follicular and papillary thyroid carcinoma cell lines.

Platelet-derived growth factor receptor (PDGFR) can bind to its ligand and consequently possess a kinase activity, and which is associated with the carcinogenesis of different cell types, including astrocytomas, oligodendrogliomas, and glioblastoma. In a cDNA microarray analysis, we observe the over-expressed mRNA of both PDGF-A and PDGF-alpha receptor in thyroid carcinoma cells. And the elevated protein expressions of PDGF-A and PDGF-alpha receptor in thyroid carcinoma cells were also confirmed by a Western blot analysis. The phosphorylation of PDGF-alpha receptor evaluated by an antibody against Tyr 720-phosphate was found in thyroid carcinoma cells. The tyrosine kinase activity of PDGF-alpha receptor was inhibited by tyrphostin AG1295 and showed a dose-dependent inhibition for the proliferation of thyroid carcinoma cells. These findings imply that autocrine activation of PDGF-alpha receptor plays a crucial role in the carcinogenesis of thyroid cells.

Association of hematological factors with components of the metabolic syndrome in older and younger adults.

BACKGROUND AND AIMS: This study retrospectively examined the characteristics of metabolic syndrome in an aged population and assessed the risk factors for these subjects. METHODS: A total of 1332 aged subjects (> or =65 years; mean age 71.0+/-5.0 years) were enrolled from 6903 subjects recruited from the Department of Health Management at Chang Gung Medical Center. Of these 6903 subjects, 1665 (814 females and 851 males) were diagnosed with metabolic syndrome. Whole body three-dimensional (3- D) laser scanning was employed for anthropometric measurements. Furthermore, health index (HI) was derived by the following equation: HI = (body weight x 2 x waist area) / [body height2 x (breast area + hip area)]. RESULTS: Among the 6903 subjects, no significant difference in gender was noted between groups with and without metabolic syndrome (p=0.142). For subjects >64 years, the incidence of metabolic syndrome in females is higher than in males. Subjects are categorized into four groups based on age and whether they had metabolic syndrome. Group A (4402 cases) consists of subjects <65 years old without metabolic syndrome. Group B (836 cases) comprises subjects >64 years old and without metabolic syndrome. Group C (1169 cases) contains subjects <65 years old with metabolic syndrome and group D (496 cases) is composed of subjects >64 years old with metabolic syndrome. Of the aged 1332 subjects, 595 were females (mean age, 70.6+/-4.6 years) and 737 were males (mean age, 71.3+/-5.3years), 37.2% (496/1332) had metabolic syndrome, 19.9% had DM and 21.8% had hypertension. These subjects had decreased BMI with age. Additionally, WHR peaked at an age range of 75-79 years. Of the aged subjects, also overweight, 42.8% and 33.6% were diagnosed with hypertension and DM, respectively; both ratios higher than those for non-overweight subjects (25.3% and 26.2%, respectively). Of the four groups in this study, the ratios for DM, hypertension, and WHR, HI, and LDL levels progressively increased through groups A to D. WBC count differs statistically significantly between these groups. Statistical analysis of WBC count, RBC and hemoglobin (Hb) with different parameters demonstrates significant elevation of WBC counts with the components of metabolic syndrome in aged subjects. CONCLUSIONS: WBC count, RBC count and Hb are associated with metabolic syndrome components in younger and old adults of both genders. The incidence of metabolic syndrome marker increased after menopause onset in the female population in this study.

Diagnosis and therapeutic strategy for papillary thyroid microcarcinoma.

HYPOTHESIS: Total thyroidectomy followed by radioactive iodine I 131 treatment is effective in papillary thyroid microcarcinoma (PTM) with lymph node or extrathyroid invasion. DESIGN: Retrospective study. SETTING: Chang Gung Medical Center, Linkou, Taiwan. PATIENTS: A total of 227 patients with PTM, categorized into high-risk (n = 12) and low-risk (n = 215) groups according to age, metastases, extent, and size criteria. INTERVENTIONS: Diagnosis and treatment of PTM. MAIN OUTCOME MEASURES: Time and method of diagnosis, operative method, metastases, and survival. RESULTS: In 51 patients, PTM was identified on preoperative fine-needle aspiration cytology; in 75 patients, diagnosed in frozen sections during operation; and in 101 patients, diagnosed incidentally in the final histopathological examination. Among these 3 groups, 18% (9/51), 17% (13/75), and 78% (79/101), respectively, underwent subtotal thyroidectomy or lobectomy for tumors. Four cases (1.8%) displayed distant metastases at diagnosis. Only 0.9% of patients with PTM (2 of 227) died of thyroid cancer. One hundred eighty-nine cases of PTM were confined to the thyroid, 22 had lymph node metastases, and 16 showed extrathyroid extension, including soft-tissue invasion and distant metastases. Sex, operative methods, follow-up status, and mortality showed differences in these groups. Five of 227 patients remained in non-disease-free status at follow-up. CONCLUSIONS: Approximately 10% of PTMs exhibited progressive clinical courses, while less than 1% resulted in mortality. Age, sex, and postoperative thyroglobulin level were the main prognostic factors in the high-risk group of patients with PTM. Conservative treatment of the incidental finding of PTM after suitable postoperative assessment is justified.

Correlation of the dysmetabolic risk factors with different anthropometric measurements.

Metabolic syndrome is a common disorder in Taiwan. For this study 431 subjects were randomly selected from visitors to the Department of Health Management. Blood pressure, blood glucose, lipid, uric acid levels and anthropometric measurements with immunoreactive insulin (IRI) and leptin levels were all correlated. We randomly selected 431 subjects who visited the Department of Health Management. Whole body three-dimensional (3-D) laser scanner scans were employed for the anthropometric measurements. The metabolic index (MI) was designed using anthropometric parameters. Of the 431 subjects, 50% had displayed a body mass index (BMI) equal to or exceeding 25 kg/m2. Pearson correlation coefficient and multiple regression analysis revealed that MI constituted another index for correlating metabolic parameters by comparing MI with BMI and waist circumference to hip circumference ratio (WHR). Most data related to metabolic syndrome showed statistically significant differences between high and low IRI groups, comprising uric acid, total cholesterol, fasting plasma glucose, triglyceride, LDL, Chol/HDL ratio, and LDL/HDL ratio. Both IRI and leptin revealed statistical association with BMI, WHR, waist cross section area to hip cross section area ratio (WHAR), and MI in the study. Hypercholesterolemia appeared in 14.6% of the subjects. Elevated low-density lipoprotein (> or = 130 mg/dL) affected 36.9% of the subjects. In conclusion, MI calculated from 3-D body scanner correlated with many important metabolic risk factors and associated with clinical disorders like DM, hyperlipidemia, hyperuricemia and hypertension.

Comparison of three-dimensional anthropometric body surface scanning to waist-hip ratio and body mass index in correlation with metabolic risk factors.

In this study, we used a three-dimensional (3D) body scanner to evaluate subjects with central obesity. These measurements were correlated with blood pressure, blood glucose, lipid, and uric acid levels. We randomly selected 1,204 subjects who visited the Department of Health Management at Chang Gung Medical Center in Linkou. The health index (HI) was calculated as HI = (body weight x 2 x waist profile area)/[body height(2) x (breast profile area + hip profile area)]. Among the 1,204 subjects, body mass index (BMI) equal to or greater than 30 kg/m(2) was found in 8.3% of the subjects. Pearson correlation coefficient studies revealed that HI was a better index for correlating metabolic parameters than BMI and waist-to-hips girth ratio. Of the 1,204 subjects, 9.5% (114) had diabetes mellitus, according to American Diabetes Association criteria. The percentages of men and women with total cholesterol greater than or equal to 245 mg/dL were almost the same (11.0% vs. 11.1%). Elevated low-density lipoprotein (> or =130 mg/dL) was found in 36.9% (444) of subjects. In conclusion, HI as determined by 3D scanning, is another method to predict these metabolic abnormalities. Further prospective long-term follow-up study is needed to determine the relationships of 3D body scanning data and HI to blood pressure, blood glucose, lipid, and uric acid levels.

Significance of postoperative serum thyroglobulin levels in patients with papillary and follicular thyroid carcinomas.

BACKGROUND AND OBJECTIVES: Although there are many factors that affect postoperative serum levels of thyroglobulin (Tg), such levels have been previously used to detect recurrence of papillary and follicular thyroid carcinomas. This study was conducted to elucidate the significance of postoperative levels of Tg in patients with clinical presentations of papillary thyroid carcinoma, follicular thyroid carcinomas, or both. METHODS: To collect data pertaining to patients with thyroid cancer who were treated in Chang Gung Medical Center in Linkou, Taiwan, records relating to a total of 847 patients with pathologically verified papillary or follicular thyroid cancer, all of whom received total thyroidectomy and thyroid remnant ablation with radioactive iodide ((131)I), were studied. To evaluate the clinical significance of postoperative levels of Tg, the patients were categorized into three groups based on postoperative Tg level. Group A was classified as those demonstrating a 1-month postoperative Tg levels less than 1 ng/ml. Group B patients were classified as those displaying a 1-month postoperative Tg levels greater than or equal to 1 ng/ml, but less than 10 ng/ml. Group C patients were classified as those exhibiting a 1-month postoperative Tg levels great than or equal to 10 ng/ml. RESULTS: Of the patients in group A, none presented with distant metastases at the time of diagnosis or during the follow-up period. In group B, 15 patients (3.5%) died of thyroid cancer. In this group, tumor size was an important factor in cancer-related mortality, diagnostic clinical class, and follow-up status. Of the 491 patients in group C, 49 (10.0%) patients died of thyroid cancer. Among the patients in group C, age, histopathologic type, stage of diagnosis, and follow-up Tg values were important factors. Among groups A, B, and C, there were 161 (95.8%), 253 (76.4%), and 129 (37.1%) patients, respectively, with disease-free status at the end of 1998. CONCLUSIONS: Postoperative serum Tg levels can be used as a prognostic indicator in patients with papillary and follicular thyroid cancer. For patients with Tg levels greater than or equal to 10 ng/ml, Tg levels are a useful marker to predict prognosis.