Cooperative Subtype Switch of Thyroid Hormone Receptor and Nuclear Receptor Corepressor Related Epithelial–Mesenchymal Transition in Papillary Thyroid Cancer

Background and Objectives@#Although thyroid hormones affect human cancer progression, the regulatory mechanism of thyroid hormone receptors in carcinogenesis has not been elucidated. This study aimed to evaluate the expression pattern of the thyroid hormone receptor (TR) and its corepressors, and to investigate the clinical and biological functions of TR. @*Materials and Methods@#Transcriptomic and clinical data for thyroid cancer were downloaded from The Cancer Genome Atlas. Paraffin-embedded tissue sections from patients who underwent thyroidectomy were used for immunohistochemistry. BCPAP cells were treated with T3 to investigate the thyroid hormone target genes. Thyroid hormone receptor alpha (THRA) and Thyroid hormone receptor beta (THRB) were knocked down by transient siRNA transfection. @*Results@#THRA and THRB expression was lower in thyroid cancer tissues than in normal tissues. However, strong focal staining of TRβ was observed in the invasive front. High THRB expression was associated with high Silencing Mediator for Retinoid or Thyroid hormone receptor (SMRT) expression, older age, a high MACIS (distant Metastasis, patient Age, Completeness of resection, local Invasion, and tumor Size) score, more aggressive histological subtypes, more frequent extra-thyroidal extension, and advanced TNM stage. THRB expression was positively correlated with Hypoxia Inducible Factor 1 Subunit Alpha (HIF1A), L1 Cell Adhesion Molecule (L1CAM), and Lysyl Oxidase (LOX) expression. Thyroid hormone-induced HIF1A, L1CAM, and LOX upregulation was abolished by siTHRB but not siTHRA in BCPAP cells. High SMRT and high THRB groups (SMRT/THRB) presented more aggressive clinical features and showed an upregulation of HIF1A, L1CAM, and LOX, as well as of epithelial-mesenchymal transition (EMT)-related genes, causing changes in the tumor microenvironment. @*Conclusion@#Cooperative subtype switching from NCOR1/THRA to SMRT/THRB was thus related to aggressive clinical and molecular features, possibly related to EMT and EMT-related tumor microenvironment.

Liver X Receptor β Related to Tumor Progression and Ribosome Gene Expression in Papillary Thyroid Cancer

Background@#Intracellular lipid deposition has been reported in thyroid glands in obese animal and human. To understand the regulatory mechanism of lipid metabolism in thyroid cancer, we investigated the expression status of liver X receptor (LXR) and analyzed its clinicopathological characteristics and molecular biological features. @*Methods@#Expression status of LXR and its transcriptional targets in human cancers were analyzed using The Cancer Genome Atlas (TCGA). The gene-sets related to high LXRβ expression was investigated by gene set enrichment analysis (GSEA) using Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways and gene ontology biologic process. Quantitative reverse transcription polymerase chain reaction was performed in thyroid cancer samples using our validation cohort. @*Results@#In contrast to low expression of LXRα, LXRβ was highly expressed in thyroid cancer compared to the other types of human cancers. High LXRβ expression was correlated with the expression of LXRβ transcriptional targets genes, such as apolipoprotein C1 (APOC1), APOC2, apolipoprotein E (APOE), ATP binding cassette subfamily G member 8 (ABCG8), sterol regulatory elementbinding protein 1c (SREBP1c), and SPOT14. Furthermore, High LXRβ expression group indicated poor clinicopathological characteristics and aggressive molecular biological features independently from the drive mutation status. Mechanistically, high LXRβ expression was coordinately related to ribosome-related gene sets. @*Conclusion@#The mechanistic link between LXRβ and ribosomal activity will be addressed to develop new diagnostic and therapeutic targets in thyroid cancers.

Effects of Oxytocin on Cell Proliferation in a Corticotroph Adenoma Cell Line

BACKGROUND: Oxytocin (OXT) has been reported to act as a growth regulator in various tumor cells. However, there is a paucity of data on the influence of OXT on cell proliferation of corticotroph adenomas. This study aimed to examine whether OXT affects cell growth in pituitary tumor cell lines (AtT20 and GH3 cells) with a focus on corticotroph adenoma cells. METHODS: Reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were conducted with AtT20 cells to confirm the effects of OXT on hormonal activity; flow cytometry was used to assess changes in the cell cycle after OXT treatment. Moreover, the impact of OXT on proliferating cell nuclear antigen (PCNA), nuclear factor κB, and mitogen-activated protein kinase signaling pathway was analyzed by Western blot. RESULTS: OXT treatment of 50 nM changed the gene expression of OXT receptor and pro-opiomelanocortin within a short time. In addition, OXT significantly reduced adrenocorticotropic hormone secretion within 1 hour. S and G2/M populations of AtT20 cells treated with OXT for 24 hours were significantly decreased compared to the control. Furthermore, OXT treatment decreased the protein levels of PCNA and phosphorylated extracellular-signal-regulated kinase (P-ERK) in AtT20 cells. CONCLUSION: Although the cytotoxic effect of OXT in AtT20 cells was not definite, OXT may blunt cell proliferation of corticotroph adenomas by altering the cell cycle or reducing PCNA and P-ERK levels. Further research is required to investigate the role of OXT as a potential therapeutic target in corticotroph adenomas.

Molecular Testing in Diagnosis of Thyroid Cancer / 대한내분비외과학회지

With increasing prevalence of thyroid nodules, clinicians are increasingly impelled to identify the optimal predictor of thyroid cancer, with the goal of guiding management based on assessed risk. Fine-needle aspiration cytology is the gold standard diagnostic method for thyroid nodules. However, fine-needle aspiration cytology is not perfect and adjuncts which might complement its predictive value are being investigated from several innovative perspectives. For these vigorous efforts, remarkable advances have been achieved in understanding several major biologic areas of thyroid cancer, including the molecular alterations for loss of radioiodine avidity of thyroid cancer, the pathogenic role of the MAP kinase and PI3K/Akt pathways and their related genetic alterations in thyroid tumorigenesis and pathogenesis. These exciting advances provide unprecedented opportunities for development of molecular-based novel diagnostic and therapeutic strategies for thyroid cancer. The common somatic genetic changes in thyroid cancer of follicular cell origin (RET/PTC, NTRK, RAS, BRAF, PAX8-PPARgamma) are generally mutually exclusive, with distinct genotype-histologic subtype associations of thyroid cancer. Mutation analysis in fine needle aspiration samples has been applied to improve the diagnostic accuracy. In studies regarding gene expression profiling, aberrant gene methylation and miRNA have shown significant progress toward identification of biomarkers that could improve the accuracy of fine needle aspiration cytology in the evaluation of patients with thyroid nodule and prediction of disease aggressiveness. Future clinical trials evaluating the accuracy and cost-effectiveness of applying these biomarkers in the management of thyroid neoplasm should be considered.

Circadian Rhythm Disruption and Metabolic Syndrome / 임상당뇨병

Metabolic syndrome is a complex disorder and an emerging clinical challenge. It is induced by the interplay of genetic and environmental factors. Recently, evidence has emerged to suggest that circadian rhythm disruption is a new risk factor to explain the increased incidence of metabolic syndrome. This review summarizes circadian rhythm biology and the evidence linking circadian rhythm disruptions to metabolic syndrome, as related to lipid metabolism, glucose homeostasis, and cardiovascular function. Further understanding of circadian rhythm will aid the development of novel therapeutic strategies for metabolic syndrome.

Clinical implications of follicular and Hurthle cell carcinoma in an iodine-sufficient area

No abstract available.

Follicular and Hurthle cell carcinoma of the thyroid in iodine-sufficient area: retrospective analysis of Korean multicenter data

BACKGROUND/AIMS: Follicular thyroid carcinoma (FTC) and Hurthle cell carcinoma (HCC) of the thyroid are relatively uncommon thyroid malignancies in iodine-sufficient areas. In this study we evaluated the clinical behavior, prognostic factors and treatment outcomes of FTC and HCC in Korea. METHODS: This multicenter study included 483 patients with FTC and 80 patients with HCC who underwent an initial surgery between 1995 and 2006 in one of the four tertiary referral hospitals in Korea. We evaluated clinicopathological factors associated with distant metastases and recurrence during a median of 6 years of follow-up. RESULTS: HCC patients were significantly older (49 years vs. 43 years; p < 0.001) and had more lymphovascular invasions (22% vs. 14%; p = 0.03) compared with FTC patients. Distant metastases were confirmed in 40 patients (8%) in the FTC group and in two patients (3%) in the HCC group (p = 0.07). Distant metastases were significantly associated with older age, widely invasive cancer and extrathyroidal invasion. Only 14 patients (3%) had recurrent disease and there was no significant difference between FTC and HCC groups (p = 0.38). Recurrence was associated with larger tumor size and cervical lymph node metastasis. CONCLUSIONS: HCC patients were older and had more lymphovascular invasions than FTC patients. However, FTC and HCC patients had similar initial clinicopathological features. Older age, wide invasiveness and extrathyroidal invasion were independent risk factors for predicting distant metastases in FTC and HCC patients.

Korean Thyroid Association Guidelines for Patients Undergoing Radioiodine Therapy for Differentiated Thyroid Cancers (First Edition, 2012) / 대한갑상선학회지

No abstract available.

NAD(P)H: Quinone Oxidoreductase 1 and NRH:Quinone Oxidoreductase 2 Polymorphisms in Papillary Thyroid Microcarcinoma: Correlation with Phenotype

PURPOSE: NAD(P)H:Quinone Oxidoreductase 1 (NQO1) C609T missense variant (NQO1*2) and 29 basepair (bp)-insertion/deletion (I29/D) polymorphism of the NRH:Quinone Oxidoreductase 2 (NQO2) gene promoter have been proposed as predictive and prognostic factors for cancer development and progression. The purpose of this study is to investigate the relationship between NQO1/NQO2 genotype and clinico-pathological features of papillary thyroid microcarcinoma (PTMC). MATERIALS AND METHODS: Genomic DNA was isolated from 243 patients; and clinical data were retrospectively analyzed. NQO1*2 and tri-allelic polymorphism of NQO2 were investigated by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. RESULTS: PTMC with NQO1*2 frequently exhibited extra-thyroidal extension as compared to PTMC with wild-type NQO1 (p=0.039). There was a significant relationship between I29/I29 homozygosity of NQO2 and lymph node metastasis (p=0.042). Multivariate analysis showed that the I29/I29 genotype was associated with an increased risk of lymph node metastasis (OR, 2.24; 95% CI, 1.10-4.56; p=0.026). CONCLUSION: NQO1*2 and I29 allele of the NQO2 are associated with aggressive clinical phenotypes of PTMC, and the I29 allele represents a putative prognostic marker for PTMC.

HIF-1alpha Expression in BRAF(V600E)-Positive Papillary Thyroid Microcarcinoma / 대한갑상선학회지

BACKGROUND AND OBJECTIVES: Recent studies have reported that vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1alpha are up-regulated in BRAF(V600E)-positive papillary thyroid carcinoma (PTC). We investigated whether papillary thyroid microcarcinomas (PTMCs) also exhibited increased expression of VEGF and HIF-1alpha. In addition, we analyzed the relationship between BRAF(V600E) mutation and clinicopathological parameters, as well as HIF-1alpha expression in PTMC. MATERIALS AND METHODS: We retrospectively selected 225 patients with PTMC. Immunohistochemical staining for HIF-1alpha and VEGF was performed using paraffinembedded PTMC tissue microarrays. BRAF(V600E) mutation status was analyzed by dideoxy sequencing. RESULTS: PTMCs larger than 0.5 cm tend to be related to aggressive clinicopathological features such as thyroid capsular invasion (p=0.023) and bilaterality (p=0.047). Immunoreactivity to HIF-1alpha (20.7%) and VEGF (30.2%) was more prominent in PTMCs as compared to normal follicular cells. However, HIF-1alpha and VEGF expression was not correlated with clinicopathological features. BRAF(V600E) mutation was found in 70.7% (159/225) of the PTMC cases. PTMCs harboring the BRAF(V600E) mutation exhibited larger tumor sizes as compared to PTMCs without the BRAF(V600E) mutation (p=0.038). However, BRAF(V600E) mutation status did not correlate with the expression of HIF-1alpha (p=0.623) or VEGF (p=0.990). CONCLUSION: HIF-1alpha and VEGF were more frequently detected in PTMCs as compared to normal thyroid tissues. However, BRAF(V600E) mutation status was not correlated with the expression of HIF-1alpha or VEGF in PTMCs.

Model Development of Papillary Thyroid Carcinoma by BRAFV600E Transgenic Mice / 대한갑상선학회지

BACKGROUND AND OBJECTIVES: The BRAFV600E mutation has been regarded as the leading cause of papillary thyroid cancer (PTC). However, the multi-step carcinogenic process induced by BRAFV600E has been remained to be elucidated in thyroid gland. In this study, to investigate staged development of papillary thyroid carcinoma, we observed the histo-pathological findings of thyroid gland from BRAFV600E transgenic mice with a period of 60 weeks. MATERIALS AND METHODS: We histologically inspected 3, 9, 20, 27, 39, 44, 48 and 60 week old BRAFV600E transgenic mice derived from FVB/N background mice with a bovine thyroglobulin promoter which are providing thyroid specific BRAFV600E expression. RESULTS: Thyroid glands from 3 and 9 week old BRAFV600E transgenic mice were enlarged and showed abnormal histologic feature such as distorted follicular architectures. The 20 and 27 week old BRAFV600E transgenic mice showed irregularly enlarged thyroid gland sprouting out above the carotid arteries. Thyroid gland derived from 39 week old mice showed reduced formation of intact follicular structure and increased solid area. Thyroid glands were entirely replaced by firm tumor mass composed of poorly differentiated cell at 44 weeks. Interestingly, we could observe tracheal invasion, surrounding muscle invasion in thyroid gland from 48 week old mice and detect lung metastasis in 60 week old mice. CONCLUSION: Thyroid specific expression of BRAFV600E induced staged development of thyroid cancer. This finding may support that BRAFV600E have a role in entire carcinogenic process such as tumor initiation, development and progression.

Bone Mineral Density in Prediabetic Men / 당뇨병

BACKGROUND: There are many studies regarding the effects of insulin on bone metabolism and changes in bone mineral density (BMD) in the setting of diabetes. The effect of prediabetes on BMD is not known. METHODS: A total of 802 men participated in the Korea Rural Genomic Cohort Study (in Geumsan County). According to the results of an oral glucose tolerance test, subjects were classified into normal, prediabetic, and diabetic categories. One hundred twenty-four subjects diagnosed with type 2 diabetes were excluded, leaving 678 subjects for the study inclusion. BMD was estimated with a quantitative ultrasonometer. RESULTS: The average BMD T scores of normal and prediabetic subjects were -1.34 +/- 1.42 and -1.33 +/- 1.30, respectively; there was no significant difference in the BMD T scores between these groups. The BMD T score was inversely associated with age and positively correlated with body weight, body mass index, total cholesterol, low density lipoprotein cholesterol, and HbA1c. On multiple linear regression analysis, low density lipoprotein cholesterol was the only statistically significant variable for prediabetes (beta = 0.007, P = 0.005). On the stepwise regression analysis, age (beta = -0.026, P < 0.001), the body mass index (beta = 0.079, P < 0.001), and low density lipoprotein cholesterol (beta = 0.004, P = 0.016) were significant variables for prediabetes. CONCLUSIONS: There was no significant difference in the BMD T score between the normal and prediabetic subjects. Further studies are needed regarding the association of fracture risk and changes in BMD with the development of overt diabetes.

Genetic Analyses of the Chimeric CYP11B1/CYP11B2 Gene in a Korean Family with Glucocorticoid-Remediable Aldosteronism

Glucocorticoid-remediable aldosteronism (GRA) is an autosomal-dominant inheritable form of hyperaldosteronism with early onset hypertension. GRA is caused by unequal crossing-over of the steroid 11beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes. As a result of chimeric gene duplication, aldosterone is ectopically synthesized in the adrenal zona fasciculata under the control of adrenocorticotropin. Here, we describe three cases of GRA in a Korean family. The proband-a 21-yr-old female-was incidentally found to have high blood pressure (170/108 mmHg). Her 46-yr-old father had been treated twice for cerebral hemorrhage at the ages of 29 and 39 yr. Her 15-yr-old brother had a 2-yr history of hypertension; however, he was never treated. Their laboratory test results showed normokalemia, hyporeninemia, hyperaldosteronism, and a high plasma aldosterone concentration-to-plasma renin activity ratio. Normal saline loading failed to suppress aldosterone secretion. However, dexamethasone administration effectively suppressed their plasma aldosterone concentrations. Following genetic analyses with PCR and direct sequencing to document the chimeric gene and crossover site, respectively, we identified CYP11B1/CYP11B2 and determined the breakpoint of unequal crossover to be located between intron 2 of CYP11B1 and exon 3 of CYP11B2.

A Case of Giant Cell Granulomatous Hypophysitis with Recurrent Hypoosmolar Hyponatremia

A 39-year-old woman presented with a 20 day history of recurrent hypoosmolar hyponatremia. Because her volume status seemed to be normal, the most suspected causes of her hyponatremia were adrenal insufficiency and hypothyroidism. Endocrinologic examination, including a combined pituitary function test, showed TSH and ACTH deficiency without GH deficiency, and hyperprolactinemia was also present. Sella MRI showed a pituitary mass, stalk thickening and loss of the normal neurohypophysial hyperintense signal on the T1 weighted image. Pathologic exam demonstrated granulomatous lesions and Langhans' multinucleated giant cells with inflammatory cell infiltration. After high dose methylprednisolone pulse therapy (1 g/day for 3 days) with subsequent prednisolone and levothyoxine replacement, there was no more recurrence of the hyponatremia. The sella MRI on the 6th month showed decreased mass size, narrowed stalk thickening and the reappearance of the normal neurohyphophysial hyperintense signal. She is currently in a good general condition and is receiving hormone replacement therapy.

Analysis of the mitochondrial D-loop sequence in a patient with thyroid Hurthle cell carcinoma and sacral bone metastasis / 대한내과학회지

Hurthle cell carcinoma, an oncocytic variant of follicular thyroid carcinoma, has a higher malignancy potential than well differentiated thyroid carcinomas. It has a tendency to metastasize easily to the lungs and bones, although isolated sacral bone metastasis has been rarely reported. Hurthle cell carcinoma has been characterized by increased mitotic activity and abundant abnormal mitochondria, which have profound mitochondrial DNA (mtDNA) alterations. In general, a well-known hypothesis is that genomic alteration, especially microsatellite instability of the mtDNA D-loop, might result in whole mtDNA instability as seen in Hurthle cell carcinoma. Recently, we experienced a case of Hurthle cell carcinoma that presented with extensive sacral bone metastasis. To investigate the relationship between mtDNA genomic instability and metastatic potential in this case, we performed direct sequencing of the mtDNA D-loop in samples extracted from normal thyroid tissue, thyroid carcinoma tissue, and sacral bone metastasis tissue. Here, we describe the results of mtDNA D-loop sequencing and present a literature review.

Body Mass Index is Associated with USF1 Haplotype in Korean Premenopausal Women

The upstream stimulatory factor 1 (USF1) gene has been shown to play an essential role as the cause of familial combined hyperlipidemia, and there are several association studies on the relationship between USF1 and metabolic disorders. In this study, we analyzed two single nucleotide polymorphisms in USF1 rs2073653 (306A>G) and rs2516840 (1748C>T) between the case (dyslipidemia or obesity) group and the control group in premenopausal females, postmenopausal females, and males among 275 Korean subjects. We observed a statistically significant difference in the GC haplotype between body mass index (BMI) > or =25 kg/m(2) and BMI <25 kg/m(2) groups in premenopausal females ( chi-square=4.23, p=0.04). It seems that the USF1 GC haplotype is associated with BMI in premenopausal Korean females.

The Effects of D-Chiro-Inositol on Glucose Metabolism in 3T3-L1 Cells / 당뇨병

BACKGROUND: The target of the treatment of metabolic syndrome and diabetes is an improvement of insulin resistance. D-chiro-inositol (DCI) plays a role in a phospholipid mediating intracellular insulin action. In the previous studies, the urine level of DCI were decreased in the diabetic animal with insulin resistance. Some clinical studies showed that DCI improved a glucose level and HbA1c. Therefore we studied the relationship between DCI and glucose metabolism, especially insulin resistance. METHODS: To investigate the mechanism of DCI affecting the glucose metabolism, we examined the effects of DCI on 2-deoxyglucose uptake, gene expression of adipocytokines and AMPK pathway by using RT-PCR and western blot in 3T3-L1 cells. RESULTS: Insulin-stimulated 2-deoxyglucose uptake increased in DCI-treated cells by about 1.2-fold (relative to the control) and was inhibited by phosphoinositide 3-kinase (PI3 Kinase) inhibitors (Wortmanin, LY294002) and AMPK inhibitor (STO-609). In Western blot analysis, it didn't show the difference of phosphorylation of Akt and AMPK between DCI-treated group and control in 3T3-L1 cells. However, DCI decreased the gene expression of resistin in 3T3-L1 cells. CONCLUSION: DCI may involve other pathway of insulin signaling, but not PI3 Kinase and AMPK signaling pathways and it may be useful in managing metabolic syndrome by improving insulin resistance through increasing glucose uptake and decreasing resistin relevant to insulin resistance.

Regulation of Inhibitors of Differentiation Family Proteins by Thyroid-Stimulating Hormone in FRTL-5 Thyroid Cells

Members of the inhibitors of differentiation (Id) family of helix-loop-helix (HLH) proteins are known to play important roles in the proliferation and differentiation of many cell types. Thyroid-stimulating hormone (TSH) regulates proliferation and differentiation by activating TSH receptor (TSHR) in thyrocytes. In this study, we found that Id2, one of the Id family proteins, is a major target for regulation by TSH in FRTL-5 thyroid cells. TSH rapidly increases the Id2 mRNA level in FRTL-5 thyroid cells but the Id2 protein showed biphasic regulatory patterns, being transiently reduced and subsequently induced by TSH treatment. Transient reduction of Id2 protein was noted within 2 hr of TSH treatment and was mediated by proteasomal degradation. Moreover, reduced Id2 expression correlated with the activity of the phosphatidylinositol 3 kinase pathway, which is activated by TSH. Although TSH increases the activity of the Id2 promoter, TSH-induced activation of this promoter was independent of c-Myc. Id2 did not alter TTF-1- and Pax-8-mediated effects on the regulation of the Tg promoter. Thus, in summary, we found that TSH regulates Id2 expression, but that Id2 does not alter the expression of thyroid-specific genes, such as Tg, in FRTL-5 thyroid cells.

Urinary Calculi Frequently Detected on Ultrasonography?

PURPOSE: Transabdominal sonography has been widely used in the diagnosis of suspected urinary calculi, assisted by secondary findings from urinary tract obstruction, but this method shows low specificity and relatively high incidence of false-positives. Recently, detection of stone itself with new Doppler finding and bladder distension on sonography has demonstrated high sensitivity. METHODS: We performed prospective transabdominal ultrasonography for emergency department patients with acute urinary colic pain over a 3 month period. With adequate bladder distension by intravenous hydration and initial spontaneous voiding drive, stones itself could be tracked along the entire length of urinary tract by emergency physician who received short-term education course. RESULTS: One hundred and thirty one patients enrolled; 86 received a sonographic exam and 57 showed urinary calculi. The detection rate of urinary calculi was 71.3%. The most common sonographic feature used in the diagnosis of urinary calculi was a distinct echogenic stone appearance within the dilated urinary tract with posterior acoustic shadowing. CONCLUSION: We concluded that detection of urinary calculi by transabdominal ultrasonography could be very useful in mbination with secondary sonographic finding from urinary tract obstruction in the evaluation of suspected urinary colic.

Correlation between Health-related Quality of Life Score and Injury Severity Score in Patients with Injury in Emergency Department

PURPOSE: The purpose of this study is to show the correlation between Health-related quality of life (HRQOL) score and injury severity score (ISS) in patients with injury in emergency department. METHODS: Between November 1, 2003, and March 2, 2004, 234 eligible injury patients who had visited our emergency center were enrolled in the study. HRQOL was assessed in 10 days after injury by Korean Short Form Health Survey- 36(KSF-36), Korean EuroQol 5 dimensions (KEQ-5D), and Korean Human Utility Index-3(KHUI-3). The severity of injury was measured by using the ISS. RESULTS: Of the 234 subjects, 149(63.7%) were men and 85(36.3%) were women, with mean(+/-SD) age of 46.1(+/-15.3) and mean ISS(+/-SD) of 4.54(+/-3.98). The KEQ-5D and KHUI-3 scores adjusted by ISS in patients with medical operation or hospitalization were significantly lower than those in patients without medical operation or hospitalization. All HRQOL scores except KSF-36 physical component summary (PCS) and general health (GH) score were significantly lower in patients group with high ISS than in patients group with low ISS. KEQ-5D and KHUI-3 had significant negative correlation with ISS (r=-0.58,-0.52). But there were no significant correlation between KSF-36 score and ISS. CONCLUSION: In this study, we observed that KEQ-5D and KHUI-3 scores in patients with injury were significantly correlated with ISS. However, to define the more definite feature of HRQOL in patients with injury, the study with more and large epidemiologic controlled injury group and detailed variable adjustment should be done.