1.A 10-Gene Signature to Predict the Prognosis of Early-Stage Triple-Negative Breast Cancer
Chang Min KIM ; Kyong Hwa PARK ; Yun Suk YU ; Ju Won KIM ; Jin Young PARK ; Kyunghee PARK ; Jong-Han YU ; Jeong Eon LEE ; Sung Hoon SIM ; Bo Kyoung SEO ; Jin Kyeoung KIM ; Eun Sook LEE ; Yeon Hee PARK ; Sun-Young KONG
Cancer Research and Treatment 2024;56(4):1113-1125
Purpose:
Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal-type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies.
Materials and Methods:
In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing.
Results:
By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor β diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores.
Conclusion
Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.
2.Impact of Evolutionary Changes in Nonalcoholic Fatty Liver Disease on Lung Function Decline
Hyun Woo LEE ; Goh Eun CHUNG ; Bo Kyung KOO ; Hyungtai SIM ; Murim CHOI ; Dong Hyeon LEE ; Seung Ho CHOI ; Soo Heon KWAK ; Deog Kyeom KIM ; Won KIM ; On behalf of the Innovative Target Exploration of NAFLD (ITEN) consortium
Gut and Liver 2023;17(1):139-149
Background/Aims:
A relationship between fatty liver and lung function impairment has been identified, and both are independently associated with metabolic dysfunction. However, the temporal relationship between changes in fatty liver status and lung function and their genome-wide association remain unclear.
Methods:
This longitudinal cohort consisted of subjects who received serial health check-ups, including liver ultrasonography and spirometry, for ≥3 years between 2003 and 2015. Lung func-tion decline rates were classified as “slow” and “accelerated” and compared among four different sonographic changes in steatosis status: “normal,” “improved,” “worsened,” and “persistent.” A genome-wide association study was conducted between the two groups: normal/improved steatosis with a slow decline in lung function versus worsened/persistent steatosis with an accelerated decline in lung function.
Results:
Among 6,149 individuals, the annual rates of decline in forced vital capacity (FVC) and forced expiratory volume measured in the first second of exhalation (FEV 1 ) were higher in the worsened/persistent steatosis group than in the normal/improved steatosis group. In multivariable analysis, persistent or worsened status of fatty liver was significantly associated with accelerated declines in FVC (persistent status, odds ratio [OR]=1.22, 95% confidence interval [CI]=1.04–1.44; worsened status, OR=1.30, 95% CI=1.12–1.50), while improved status of fatty liver was significantly associated with slow declines in FEV 1 (OR=0.77, 95% CI=0.64–0.92). The PNPLA3 risk gene was most strongly associated with steatosis status change and accelerated declines in FVC (rs12483959, p=2.61×10 -7 ) and FEV 1(rs2294433, p=3.69×10 -8 ).
Conclusions
Regression of fatty liver is related to lung function decline. Continuing efforts to improve fatty liver may preserve lung function, especially for subjects with a high genetic risk.
3.Inhaled Corticosteroids in Asthma and the Risk of Pneumonia
Min Hye KIM ; Chin Kook RHEE ; Ji Su SHIM ; So Young PARK ; Kwang Ha YOO ; Bo Yeon KIM ; Hye Won BAE ; Yun Su SIM ; Jung Hyun CHANG ; Young Joo CHO ; Jin Hwa LEE
Allergy, Asthma & Immunology Research 2019;11(6):795-805
PURPOSE: Asthma is a common disease that is expensive and burdensome for patients. Inhaled corticosteroids (ICS) are the most important drugs for asthma treatment and are often prescribed long-term. However, the use of ICS has been reported to increase pneumonia, though this remains controversial. We evaluated whether the use of ICS increases the risk of pneumonia in asthmatic patients using the Health Insurance Review and Assessment Service (HIRA) database in Korea. METHODS: The Asthma Management Adequacy Assessment was performed by the HIRA in Korea. Patients with claimed insurance benefits for asthma disease codes and who were prescribed asthma medications more than 2 times were enrolled. Patient demographics, asthma medications, healthcare use, and complications were analyzed. RESULTS: The total number of asthma patients was 831,613. Patients using ICS were older and had more comorbidities than those not using ICS; they also visited outpatient clinics and emergency departments, and were more often hospitalized. Pneumonia and other complications occurred more often in patients using ICS, and they used more respiratory medications, except for theophylline. Multiple logistic regression analysis showed that ICS prescription was associated with pneumonia (odds ratio, 1.38; 95% confidence interval, 1.36-1.41). Age, sex, medical care, use of secondary and tertiary hospitals, and hospitalization due to asthma in the previous year were also associated with pneumonia. CONCLUSIONS: ICS use was associated with increasing pneumonia in asthmatic patients in Korea. Therefore, it is critical to acknowledge that the use of ICS may increase the risk of pneumonia and should be meticulously monitored in asthmatics.
Adrenal Cortex Hormones
;
Ambulatory Care Facilities
;
Asthma
;
Comorbidity
;
Delivery of Health Care
;
Demography
;
Emergency Service, Hospital
;
Hospitalization
;
Humans
;
Insurance Benefits
;
Insurance, Health
;
Korea
;
Logistic Models
;
Pneumonia
;
Prescriptions
;
Steroids
;
Tertiary Care Centers
;
Theophylline
4.Comparative Evaluation of Hormones and Hormone-Like Molecule in Lineage Specification of Human Induced Pluripotent Stem Cells
Seon A CHOI ; Ju Hyun AN ; Seung Hwan LEE ; Geun Hui LEE ; Hae Jun YANG ; Pil Soo JEONG ; Jae Jin CHA ; Sanghoon LEE ; Young Ho PARK ; Bong Seok SONG ; Bo Woong SIM ; Young Hyun KIM ; Ji Su KIM ; Yeung Bae JIN ; Jae Won HUH ; Sang Rae LEE ; Jong Hee LEE ; Sun Uk KIM
International Journal of Stem Cells 2019;12(2):240-250
BACKGROUND AND OBJECTIVES: Proficient differentiation of human pluripotent stem cells (hPSCs) into specific lineages is required for applications in regenerative medicine. A growing amount of evidences had implicated hormones and hormone-like molecules as critical regulators of proliferation and lineage specification during in vivo development. Therefore, a deeper understanding of the hormones and hormone-like molecules involved in cell fate decisions is critical for efficient and controlled differentiation of hPSCs into specific lineages. Thus, we functionally and quantitatively compared the effects of diverse hormones (estradiol 17-β (E2), progesterone (P4), and dexamethasone (DM)) and a hormone-like molecule (retinoic acid (RA)) on the regulation of hematopoietic and neural lineage specification. METHODS AND RESULTS: We used 10 nM E2, 3 μM P4, 10 nM DM, and 10 nM RA based on their functional in vivo developmental potential. The sex hormone E2 enhanced functional activity of hematopoietic progenitors compared to P4 and DM, whereas RA impaired hematopoietic differentiation. In addition, E2 increased CD34⁺CD45⁺ cells with progenitor functions, even in the CD43⁻ population, a well-known hemogenic marker. RA exhibited lineage-biased potential, preferentially committing hPSCs toward the neural lineage while restricting the hematopoietic fate decision. CONCLUSIONS: Our findings reveal unique cell fate potentials of E2 and RA treatment and provide valuable differentiation information that is essential for hPSC applications.
Dexamethasone
;
Humans
;
Induced Pluripotent Stem Cells
;
Pluripotent Stem Cells
;
Progesterone
;
Regenerative Medicine
;
Tretinoin
5.Usefulness of Inflammatory Markers for the Prediction of Postherpetic Neuralgia in Patients with Acute Herpes Zoster.
Jun Young KIM ; Gyeong Hun PARK ; Min Ji KIM ; Hyun Bo SIM ; Weon Ju LEE ; Seok Jong LEE ; Shin Woo KIM ; Young Hoon JEON ; Yong Hyun JANG ; Do Won KIM
Annals of Dermatology 2018;30(2):158-163
BACKGROUND: Increasing evidence suggests a pivotal role for neuronal inflammation in response to replicating varicella zoster virus in the development of postherpetic neuralgia (PHN). OBJECTIVE: In this study, we investigated the value of serum levels of various inflammatory markers in acute herpes zoster (HZ) as predictors for the development of PHN. METHODS: A total of 116 patients with acute HZ were enrolled in this study. We measured scores on the pain visual analogue scale (VAS) at baseline and at 1, 3, and 6 months after diagnosis of HZ. We defined PHN as pain greater than 1 on the VAS lasting for more than 6 months. Serum samples for laboratory assay, including complete blood count were obtained at the initial visit. Correlations between the levels of each inflammatory marker and the development of PHN were evaluated. RESULTS: Levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), lymphocyte count, and albumin showed significant correlations with development of PHN in univariate analysis. Levels of ESR, CRP, and lymphocyte count also showed significant correlations in multivariate analysis. ESR level showed stronger correlations with development of PHN than levels of CRP and lymphocyte count. CONCLUSION: In this study, we confirmed that elevated ESR was an independent and significant predictor of PHN in patients with acute HZ. To validate these results, further well-designed, randomized clinical trials are needed.
Blood Cell Count
;
Blood Sedimentation
;
C-Reactive Protein
;
Diagnosis
;
Herpes Zoster*
;
Herpesvirus 3, Human
;
Humans
;
Inflammation
;
Lymphocyte Count
;
Multivariate Analysis
;
Neuralgia, Postherpetic*
;
Neurons
6.Deep Benign Fibrous Histiocytoma Showing Multiple Metastases.
Hyun Bo SIM ; Min Ji KIM ; Soo Yuhl CHAE ; Weon Ju LEE ; Seok Jong LEE ; Do Won KIM ; Yong Hyun JANG
Korean Journal of Dermatology 2017;55(5):301-304
Some morphological variants of benign fibrous histiocytoma (dermatofibroma) present with distinct clinical features. In particular, atypical, aneurysmal, and cellular fibrous histiocytoma are associated with a significant risk of local recurrence. Furthermore, very rarely, cutaneous fibrous histiocytoma can lead to metastatic disease. Deep benign fibrous histiocytoma is an uncommon and poorly recognized clinical subtype that arises in subcutaneous or deep soft tissue. Deep benign fibrous histiocytoma has many histologic features in common with cellular fibrous histiocytoma. Deep benign fibrous histiocytoma recurs in approximately 20% of cases and may rarely metastasize. We report a rare case of deep benign fibrous histiocytoma with metastatic potential in a 38-year-old man who presented with a 2-year history of a recurrent hard mass on his left shoulder.
Adult
;
Aneurysm
;
Histiocytoma, Benign Fibrous*
;
Humans
;
Neoplasm Metastasis*
;
Recurrence
;
Shoulder
7.House Dust Mite Sensitization Is Inversely Associated with Plasma 25-Hydroxyvitamin D3 Levels in Patients with Severe Atopic Dermatitis.
Yong Hyun JANG ; Hyun Bo SIM ; Sun Young MOON ; Weon Ju LEE ; Seok Jong LEE ; Meiling JIN ; Sang Hyun KIM ; Do Won KIM
Annals of Dermatology 2017;29(4):400-406
BACKGROUND: The relationship between atopic dermatitis (AD) and low vitamin D levels has been studied. Emerging evidence has implicated vitamin D as a critical regulator of immunity, playing a role in both the innate and cell-mediated immune systems. However, the effect of vitamin D on house dust mite (HDM) sensitization in patients with AD has not been established. OBJECTIVE: We investigated the association between vitamin D levels and HDM sensitization according to AD severity. METHODS: In total, 80 patients (43 men and 37 women) with AD were included. We classified AD severity using Rajka and Langeland scores. Laboratory tests included serum 25-hydroxyvitamin D3, total immunoglobulin E (IgE), and specific IgE antibody titer against Dermatophagoides farinae and D. pteronyssinus. RESULTS: There were no differences in vitamin D levels between the mild or moderate AD and severe AD groups. In the severe AD group, high HDM sensitization group had lower serum vitamin D levels compared to low HDM sensitization group with statistical significance. In addition, a significant negative correlation was found between vitamin D levels and HDM sensitization in the severe AD group. CONCLUSION: Our results demonstrate that low vitamin D levels may link to high HDM sensitization in patients with the severe AD. Further elucidation of the role of vitamin D in HDM sensitization may hold profound implications for the prevention and treatment of AD.
Calcifediol*
;
Dermatitis, Atopic*
;
Dermatophagoides farinae
;
Dermatophagoides pteronyssinus
;
Dust*
;
Humans
;
Immune System
;
Immunoglobulin E
;
Immunoglobulins
;
Male
;
Plasma*
;
Pyroglyphidae*
;
Vitamin D
8.A Case of Sebaceoma on the Cymba Concha.
Soo Yuhl CHAE ; Hyun Bo SIM ; Min Ji KIM ; Yong Hyun JANG ; Seok Jong LEE ; Do Won KIM ; Weon Ju LEE
Korean Journal of Dermatology 2016;54(5):389-390
No abstract available.
9.Skin Infection due to Trichophyton tonsurans Still Occurs in People in Korea but not as Outbreaks.
Weon Ju LEE ; Hyun Bo SIM ; Yong Hyun JANG ; Seok Jong LEE ; Do Won KIM ; Jae Bok JUN ; Yong Jun BANG
Journal of Korean Medical Science 2016;31(2):296-300
Since 1995, Trichophyton tonsurans has been one of the causative agents of dermatophytosis in Korea. Herein we evaluate 77 patients infected with T. tonsurans who visited an outpatient clinic between 2004 and 2014. Infections due to T. tonsurans were diagnosed by mycological examination, which included direct microscopic examination using 15% KOH and culture in potato dextrose agar complemented with 0.5% chloramphenicol. The annual prevalence of infection due to T. tonsurans was the highest in 2014 (15 cases) but remained constant in non-gladiators between 2004 and 2014. The ratio of male to female patients was 1:0.3. The spring season presented the highest incidence compared with other seasons, with 27 cases. The incidence of infections due to T. tonsurans among gladiators was highest in spring compared with the other seasons whereas the incidence in non-gladiators was the highest in the winter. The body site most commonly affected was the face. Tinea corporis was the most common subtype of dermatophytosis caused by T. tonsurans. Herein, we demonstrate that the prevalence of infection with T. tonsurans remain constant throughout the study period in Korea.
Adolescent
;
Adult
;
Aged
;
Child
;
Child, Preschool
;
Disease Outbreaks
;
Female
;
Humans
;
Infant
;
Male
;
Middle Aged
;
Prevalence
;
Republic of Korea/epidemiology
;
Retrospective Studies
;
Seasons
;
Tinea/*diagnosis/epidemiology/microbiology
;
Trichophyton/*isolation & purification
;
Young Adult
10.The Longitudinal Trend of Cardiac Surgery in Korea from 2003 to 2013.
Kyeong Soo LEE ; Chang Suk KIM ; Jong Heon PARK ; Tae Yoon HWANG ; Sang Won KIM ; Sung Bo SIM ; Kun Sei LEE
The Korean Journal of Thoracic and Cardiovascular Surgery 2016;49(Suppl 1):S1-S13
BACKGROUND: The purpose of this study was to investigate longitudinal changes of the utilization of operational and surgical medical care inside and outside a metropolitan area over 10 years, analyzing the residential areas of patients and the locations of medical facilities for major cardiovascular surgery. METHODS: Data analysis was conducted by classifying the addresses of patients and the locations of medical care facilities of metropolitan cities and provinces, using data from the National Health Insurance Corporation from January 2003 to December 2013. RESULTS: There is serious concentration of major heart surgery to medical facilities in Seoul; this problem has not improved over time. There were differences in percentages of surgical procedures performed in the metropolitan areas according to major diseases. In the case of Busan and Daegu provinces, at least 50% of the patients underwent surgery in medical facilities in the city, but there are other regions where the percentage is less than 50%. In the case of provinces, the percentage of surgical procedures performed in medical facilities in Seoul or nearby metropolitan cities is very high. CONCLUSION: Policies to strengthen the regional capabilities of heart surgery and to secure human resources are required to mitigate the concentration of patients in the capital area. Many regional multi-centers must be designated to minimize unnecessary competition among regional university hospitals and activate a win-win partnership model for medical services.
Busan
;
Coronary Artery Bypass
;
Daegu
;
Health Facilities
;
Hospitals, University
;
Humans
;
Korea*
;
National Health Programs
;
Seoul
;
Statistics as Topic
;
Thoracic Surgery*

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