High vegetable consumption and regular exercise are associated with better quality of life in patients with gout.

Background/Aims: The Gout Impact Scale (GIS), a part of the Gout Assessment Questionnaire 2.0, is used to measure gout-specific health-related quality of life (HRQOL). Although several studies have been conducted on the factors affecting the HRQOL of patients with gout, few have focused on lifestyle factors. This study aimed to investigate the correlation between lifestyle habits and HRQOL using the GIS in patients with gout. Methods: We used data from the Urate-Lowering TheRApy in Gout (ULTRA) registry, a prospective cohort of Korean patients with gout treated at multiple centers nationwide. The patients were aged ≥18 years and met the 2015 American College of Rheumatology/European League Against Rheumatism gout classification criteria. They were asked to complete a GIS and questions regarding their lifestyle habits at enrollment. Results: The study included 232 patients. 'Gout concern overall' scores in the GIS were significantly lower in patients who exercised more frequently and consumed soft drinks and meat less, and 'well-being during attack' scores were significantly lower in patients who consumed vegetables and exercised more frequently. The frequency of vegetable consumption had a negative linear relationship with the 'well-being during attack' and 'gout concern during attack' scores (p = 0.01, p = 0.001, respectively). The frequency of exercise had a negative linear relationship with the 'gout concern overall' and 'gout concern during attack' scores (p = 0.04 and p = 0.002, respectively). Conclusions: Patients with gout who frequently consumed vegetables and exercised regularly experienced less impact of gout, exhibiting a better GIS that represented HRQOL.

Approval status of essential therapeutic drugs for systemic sclerosis versus that of drugs for rheumatoid arthritis.

Objective: Systemic sclerosis, a rare disease characterized by chronic multisystem fibrosis, requires lifelong management, necessitating enough insurance coverage for the patient. Official drug approval is the first step to ensuring that the drug is covered by insurance. In this study, we investigated the approval status of essential therapeutic drugs for systemic sclerosis across eight countries and compared it with that of drugs for rheumatoid arthritis. Methods: The essential therapeutic drug lists for systemic sclerosis and rheumatoid arthritis were taken from the guidelines of the American College of Rheumatology and the European Alliance of Associations for Rheumatology. Official drug approval status for the selected drugs was confirmed by searching representative Internet databases from eight countries: the United States, the United Kingdom, Germany, France, Italy, Switzerland, Japan, and the Republic of Korea. Results: A total of 21 and 16 drugs were selected for systemic sclerosis and rheumatoid arthritis, respectively. The drug approval rates of the 21 drugs for systemic sclerosis varied among countries. Most drugs used to treat pulmonary arterial hypertension, which were developed recently and are expensive, are approved by most countries; however, most older drugs-which are still essential for management of Raynaud's phenomenon, digital ulcers, interstitial lung disease, and skin fibrosis-are not approved by most countries. By contrast, almost all of the 16 drugs used to treat rheumatoid arthritis, whether old or new, are approved by most countries. Conclusion: Approval rates for drugs used to treat systemic sclerosis, a rare disease, are much lower than those for drugs used to treat rheumatoid arthritis. Thus, approval rates of essential therapeutic drugs for systemic sclerosis need to improve, which will benefit patients by increasing the number of drugs covered by insurance.

Prediction of osteoporosis in patients with rheumatoid arthritis using machine learning.

Osteoporosis is a serious health concern in patients with rheumatoid arthritis (RA). Machine learning (ML) models have been increasingly incorporated into various clinical practices, including disease classification, risk prediction, and treatment response. However, only a few studies have focused on predicting osteoporosis using ML in patients with RA. We aimed to develop an ML model to predict osteoporosis using a representative Korean RA cohort database. The KORean Observational study Network for Arthritis (KORONA) database, established by the Clinical Research Center for RA in Korea, was used in this study. Among the 5077 patients registered in KORONA, 2374 patients were included in this study. Four representative ML algorithms were used for the prediction: logistic regression (LR), random forest, XGBoost (XGB), and LightGBM. The accuracy, F1 score, and area under the curve (AUC) of each model were measured. The LR model achieved the highest AUC value at 0.750, while the XGB model achieved the highest accuracy at 0.682. Body mass index, age, menopause, waist and hip circumferences, RA surgery, and monthly income were risk factors of osteoporosis. In conclusion, ML algorithms are a useful option for screening for osteoporosis in patients with RA.

Factors for achieving target serum uric acid levels after initiating urate-lowering therapy in patients with gout: results from the ULTRA registry.

Achieving target serum uric acid (SUA) levels is important in gout management. Guidelines recommend lowering SUA levels to < 6 mg/dL; however, many patients fail to reach this target, even with uric acid-lowering therapy (ULT). This study investigated clinical characteristics of target SUA achievers among Korean patients with gout. This study used data from the ULTRA registry, a nationwide inception cohort established in September 2021 that enrolls patients with gout who initiate ULT. Demographic, clinical, and laboratory data were collected at baseline; the 6-month follow-up. Patients were divided into two groups: target achievers (SUA level < 6 mg/dL at 6 months) and non-achievers. The mean participant (N = 117) age was 56.1 years, and 88.0% were male. At 6 months, 83 patients (70.9%) reached target SUA levels. Target achievers had better drug adherence (≥ 80%) to ULT (97.6% vs. 76.5%; p < 0.01) than non-achievers. Target non-achievers had a higher percentage of a family history of gout (32.4% vs. 10.8%; p < 0.01) and less antihypertensive agent use (38.2% vs. 59.0%; p = 0.03) than target achievers. Multivariate regression analysis revealed that good adherence to ULT, the absence of a family history of gout, and antihypertensive agent use were key factors associated with achieving target SUA levels at 6 months.

Unmet Needs of Patients With Chronic Urticaria: A Survey in Korea.

Chronic urticaria (CU) is a common problem with a high disease burden that has a significant negative impact on quality of life. Many patients are undertreated, and awareness of management strategies is low among clinicians. The present study aimed to improve understanding of CU from the patients' perspective, including the disease burden and current healthcare system use. Adult patients who presented to our referral hospital for CU treatment completed self-report questionnaires about demographics, clinical characteristics of CU, the impact of CU on daily life, unmet needs, and the history of medical service usage. This self-report survey included 127 participants (females, 57.0%; mean age, 42.0 ± 13.6 years; mean CU duration, 1.8 ± 3.4 years); 51.6% reported frequent discomfort with CU in daily life, including 44.1% of those who reported a good response to medication. More than half of the respondents reported a depressed mood and anxiety. Although 46.4% of the respondents reported that urticaria completely disappeared while on medication, only 10% were satisfied with the CU management provided by primary care hospitals. The principal cause of dissatisfaction was that they did not know the cause of CU (68.4% of patients). In total, 55% of the patients visited 2 or more hospitals before presenting to our referral hospital and 6.3% had tried folk remedies. In conclusion, most patients report that CU is not adequately controlled. Therefore, in addition to appropriate medication, information on the cause of CU, long-term treatment plan, medication safety, and expected prognosis is required to meet patients' needs.

Reliability and Validity of the Korean Version of the Gout Impact Scale.

BACKGROUND: The Gout Impact Scale (GIS), part of the Gout Assessment Questionnaire 2.0, measures gout-specific health-related quality of life (HRQOL). This study aimed to translate the GIS into Korean and validate the Korean version (K-GIS) using generic HRQOL measures. METHODS: The GIS was translated into Korean and back-translated into English. We asked patients aged 18 years or older who met the 2015 gout classification criteria to fill out the questionnaires (from January 2022 to June 2022); the K-GIS (5 scales [0-100 scores each]), along with the Korean version of Health Assessment Questionnaire (HAQ) and EuroQol-5 dimension (EQ-5D). We investigated the internal consistency, construct validity, and discriminative validity for gout characteristics of K-GIS. The K-GIS form was administrated to patients 4 weeks later to assess the test-retest reliability using the intraclass correlation coefficient (ICC). RESULTS: One hundred patients completed the questionnaire. The mean ± standard deviation age of the patients was 53.0 ± 15.1 years, and 99.0% of the patients were men. All scales had high degree of internal consistency (Cronbach's α = 0.59 to 0.96) and test-retest reliability (n = 18, ICC = 0.83 to 0.94, all P < 0.001), except for unmet gout treatment needs. Weak-to-moderate correlations were observed between the K-GIS scales and HAQ or EQ-5D (r = 0.21 to 0.46). The K-GIS scores were significantly higher in the presence of bone erosion, absence of urate-lowering therapy, serum urate levels > 6 mg/dL, frequent gout flares in the past year, and fewer comorbidities. In contrast, neither the HAQ nor the EQ-5D could discern these subsets of patients. CONCLUSION: The K-GIS is a reliable and valid HRQOL measure for patients with gout. Higher K-GIS scores were associated with clinical characteristics leading to unfavorable outcomes, which were not demonstrated by the HAQ and EQ-5D.

Assessing Quality of Life in Patients With Chronic Urticaria Through Comparisons With Patients Having Other Common Chronic Diseases.

BACKGROUND: Chronic urticaria (CU) is a common chronic inflammatory disease, but the burden on quality of life (QOL) has been underestimated. OBJECTIVE: To compare QOL among patients with CU and those with other chronic diseases. METHODS: Adult patients who visited a referral hospital for CU were enrolled. Patients completed self-reported questionnaires including clinical characteristics of chronic urticaria and the short form 36 health survey. As a comparative group, patients with rheumatoid arthritis, patients with diabetes treated with insulin, patients on maintenance hemodialysis, and healthy controls were enrolled and completed the short form 36 health survey. RESULTS: In all, 119 patients with CU were enrolled and their short form 36 scores were not significantly different from those of healthy controls. However, patients with CU with poor responses to treatment showed impaired QOL to a degree similar to that of patients with rheumatoid arthritis or insulin-treated diabetes. The patients with CU showed various clinical characteristics with respect to treatment response, accompanying symptoms, and aggravating factors. Among these factors, pain at the urticarial lesion and symptom aggravation during exercise and after the consumption of certain foods were related with lower QOL. CONCLUSIONS: Patients with CU with an incomplete response to treatment had significantly low QOL, comparable to that of patients with rheumatoid arthritis or insulin-treated diabetes. To minimize this effect, clinicians should aim to control symptoms and aggravating factors.

Cardiovascular Risks in Korean Patients with Gout: Analysis Using a National Health Insurance Service Database.

Although several epidemiologic studies have shown the association between gout and cardiovascular outcomes, specific risk factors for developing cardiovascular diseases in Asian patients with gout are undisclosed. Thus, the purpose of this study was to investigate risks of cardiovascular outcomes and its related factors in Korean patients with gout. This retrospective clinical study used sampled cohort data from the National Health Insurance Service in Korea. Patients with gout were defined as subjects enlisted with an ICD-10 code (M10). Control patients were selected by frequency matching for age, sex, and index year. Primary outcomes included ischemic heart disease (IHD), congestive heart failure, cerebrovascular disease (CVD), or transient ischemic attack. We calculated the hazard ratio (HR) using Cox regression, adjusting potential confounders including age, sex, lifestyle habits, laboratory results, and medication. We identified 3306 patients with gout and an equal number of matched controls. Multivariate Cox regression analysis showed that gout patients had increased risks of IHD (HR: 1.860, 95% CI: 1.446-2.392), acute myocardial infarction (HR: 3.246, 95% CI: 1.460-7.217), and CVD (HR: 1.552, 95% CI: 1.177-2.036). Old age, current smoking, frequent alcohol intake, high low-density lipoprotein, and diabetes mellitus increased the risk of cardiovascular outcomes, yet hypouricemic agents decreased the risk of cerebrovascular diseases. Our data corroborate that it is crucial to identify and manage traditional cardiovascular risk factors alongside lowering urate levels in patients with gout.

Analysis of treatment pattern of anti-dementia medications in newly diagnosed Alzheimer's dementia using OMOP CDM.

Anti-dementia medications are widely prescribed to patients with Alzheimer's dementia (AD) in South Korea. This study investigated the pattern of medical management in newly diagnosed patients with AD using a standardized data format-the Observational Medical Outcome Partnership Common Data Model from five hospitals. We examined the anti-dementia treatment patterns from datasets that comprise > 5 million patients during 2009-2019. The medication utility information was analyzed with respect to treatment trends and persistence across 11 years. Among the 8653 patients with newly diagnosed AD, donepezil was the most commonly prescribed anti-dementia medication (4218; 48.75%), followed by memantine (1565; 18.09%), rivastigmine (1777; 8.98%), and galantamine (494; 5.71%). The rising prescription trend during observation period was found only with donepezil. The treatment pathways for the three cholinesterase inhibitors combined with N-methyl-D-aspartate receptor antagonist were different according to the drugs (19.6%; donepezil; 28.1%; rivastigmine, and 17.2%; galantamine). A 12-month persistence analysis showed values of approximately 50% for donepezil and memantine and approximately 40% for rivastigmine and galantamine. There were differences in the prescribing pattern and persistence among anti-dementia medications from database using the Observational Medical Outcome Partnership Common Data Model on the Federated E-health Big Data for Evidence Renovation Network platform in Korea.

Epidemiology and Treatment of Systemic Sclerosis in Korea.

Systemic sclerosis (SSc), a rare, chronic progressive systemic autoimmune disease of unknown etiology, is characterized by autoimmunity, tissue fibrosis, and obliterative vasculopathy. SSc can affect all major organs including the skin, blood vessels, lung, heart, kidneys, and gastrointestinal tract. Our understanding of its pathogenesis has increased over the past few decades, leading to improved diagnosis and treatment. However, the mortality rate of SSc remains considerable, mainly due to cardiopulmonary causes. A growing body of evidence suggests that geographical, regional, and ethnic differences could affect the epidemiology, clinical characteristics and prognosis of SSc. Although Korean data of this issue are lacking, a considerable amount of research has been published by many Korean researchers. To establish treatment strategies for Korean patients, extensive Korean research data are needed. This review summarizes the prevalence, incidence, mortality, and clinical and laboratory manifestations of Korean patients with SSc and discusses the current trends in evidence-based treatment and recommendations.

Cancer risk in Korean patients with gout.

BACKGROUND/AIMS: Using a nationwide cohort, we investigated the cancer risk in Korean patients with gout. METHODS: Data were obtained from the Korean National Health Insurance Service Database. Patients with gout were defined as those aged ≥ 20 years who were diagnosed with gout and received anti-gout medication (allopurinol, colchicine, and benzbromarone) between 2008 and 2010. Patients with nail disorders were randomly assigned to a control group (1:1 ratio) after frequency matching for age and sex. Cancer incidence was then investigated between 2012 and 2018. Cox proportional hazard regression analysis was used to investigate the association between gout and cancer after adjusting for concomitant diseases. RESULTS: This study included 179,930 patients with gout and an equal number of matched controls. The incidence of overall cancer was higher in patients with gout than in controls (incidence rate ratio, 1.08). Cox proportional hazards regression analysis showed that gout was associated with a hazard ratio of 1.053 (95% confidence interval ,1.031 to 1.077) after adjusting for concomitant diseases. CONCLUSION: Gout was associated with a significantly high risk of cancer, especially esophageal, stomach, colon, liver, pancreatic, lung, ovarian, renal, and bladder cancers.

Patient Perspectives and Preferences Regarding Gout and Gout Management: Impact on Adherence.

BACKGROUND: Patient-centered management is becoming increasingly important in gout, but there are limited studies exploring patients' perspectives and preferences. We aimed to investigate patients' perspectives and preferences regarding gout and gout management, and their impacts on adherence to urate lowering therapy (ULT). METHODS: A paper-based survey was performed in patients with gout seen at the rheumatology outpatient clinics of 16 tertiary hospitals. The survey included questions regarding demographics, comorbidities, gout attacks, current treatment and adherence, and patients' perspectives and preferences regarding gout and gout management. Multivariate regression analysis was performed to determine the factors associated with ULT adherence. RESULTS: Of 809 surveyed patients with gout, 755 (94.5%) were using ULT. Among those using ULT, 89.1% had ≥ 80% adherence to ULT. Majority of the patients knew management strategies to some extent (94.8%), perceived gout as a life-long disease (91.2%), and were making efforts toward practicing at least one lifestyle modification (89.2%). Most patients (71.9%) obtained information about gout management during their clinic visits. Approximately half of the patients (53.6%) preferred managing their disease with both ULT and lifestyle modification, 28.4% preferred ULT only, and 17.4% preferred lifestyle modification only. Adherence was better in patients with older age (odds ratio [OR], 1.03), those with better knowledge of gout management strategies (OR, 3.56), and those who had preference for ULT (OR, 2.07). CONCLUSION: Patients' perspectives and management preferences had high impacts on adherence to ULT in gout. Consideration of patients' perspectives and preferences is important for achieving the desired clinical outcome in gout.

Quality Indicators for Evaluating the Health Care of Patients with Rheumatoid Arthritis: a Korean Expert Consensus.

BACKGROUND: There is increasing interest in the quality of health care and considerable efforts are being made to improve it. Rheumatoid arthritis (RA) is a disease that can result in favorable outcomes when appropriate diagnosis and treatment are provided. However, several studies have shown that RA is often managed inappropriately. Therefore, the Korean College of Rheumatology aimed to develop quality indicators (QIs) to evaluate and improve the health care of patients with RA. METHODS: Preliminary QIs were derived based on the existing guidelines and QIs for RA. The final QIs were determined through two separate consensus meetings of experts. The consensus was achieved through a panel of experts who voted using the modified Delphi method. RESULTS: Fourteen final QIs were selected among 70 preliminary QIs. These included early referral to and regular follow-up with a rheumatologist, radiographs of the hands and feet, early initiation and maintenance of disease-modifying anti-rheumatic drug (DMARD) therapy, periodic assessment of disease activity, screening for drug safety and comorbidities, including viral hepatitis and tuberculosis before biologic DMARD therapy, periodic laboratory testing, supplementation with folic acid, assessment of the risk for cervical spine instability before general anesthesia, patient education, and specialized nurse. CONCLUSION: These QIs can be used to assess and improve the quality of health care for patients with RA.

Presence of tophi is associated with a rapid decline in the renal function in patients with gout.

We aimed to compare clinical characteristics of patients with and without tophi at the time of the diagnosis of gout and investigate the association of tophi and renal function in gout patients. The patients who were first diagnosed with gout at the Kangwon National University Hospital were retrospectively studied. Patients were divided into 2 groups according to the presence of tophi at the diagnosis. We compared clinical characteristics and the progression of renal dysfunction between the two groups. Of 276 patients, 66 (25.5%) initially presented with tophi. Tophi group was older, had a longer symptom duration, and a higher prevalence of multiple joint involvement than those without tophi. In multivariate logistic regression analysis, prolonged symptom duration and multiple joint involvement were significantly associated with increased risk of formation of tophi. The decline in the eGFR was more prominent in patients with tophi than in those without (- 4.8 ± 14.5 vs. - 0.7 ± 11.9 ml/min/1.73 m2/year, respectively; P = 0.039). The presence of tophi was significantly associated with a rapid decline in the eGFR (ß = - 0.136; P = 0.042). In conclusion, the presence of tophi was associated with a rapid declining renal function. Therefore, an early diagnosis and closely monitoring of renal function might be important in gout patients with tophi.

A clinical comparison of an endothelin receptor antagonist and phosphodiesterase type 5 inhibitors for treating digital ulcers of systemic sclerosis.

OBJECTIVES: To assess the efficacy of an endothelin receptor antagonist (ERA) and phosphodiesterase type5 inhibitors (PDE5is) for treating SSc-related digital ulcers (DUs). METHODS: This prospective, multicentre, observational cohort study recruited patients with active SSc-related DUs from 13 medical centres in South Korea. The primary outcome was time to cardinal ulcer (CU) healing. A secondary outcome was time to new DU occurrence. Patients were followed up 4, 8, 12 and 24 weeks after treatment initiation. RESULTS: Sixty-three patients were analysed. Their mean age was 49.9 years (s.d. 11.4) and 49 were female. Twenty-eight had limited SSc. Forty-nine patients received ERA, 11 received a PDE5i (9 sildenafil, 1 udenafil and 1 tadalafil) and 3 received other medication. The hazard ratio (HR) for time to CU healing in the ERA group vs the PDE5i group was 0.75 (95% CI 0.35, 1.64; P = 0.47) in an unadjusted model and 0.80 (95% CI 0.36, 1.78; P = 0.59) in a model adjusted for age, sex, use of calcium channel blockers (CCBs), total DU number and initial CU area. The HR for new DU development in the ERA group vs the PDE5i group was 0.39 (95% CI 0.16, 0.93; P = 0.03) in an unadjusted model and 0.32 (95% CI 0.13, 0.81; P = 0.02) in an adjusted model. No patients receiving CCBs developed new DUs at 24 weeks. CONCLUSION: Time to CU healing is comparable for ERA and PDE5i. ERAs are more effective in reducing new DU occurrence than PDE5is. CCBs may be effective as a background medication.

Role of Synovial Exosomes in Osteoclast Differentiation in Inflammatory Arthritis.

This study aimed to investigate the characteristics of exosomes isolated from synovial fluid and their role in osteoclast differentiation in different types of inflammatory arthritis. Exosomes isolated from synovial fluid of rheumatoid arthritis (RA), ankylosing spondylitis (AS), gout, and osteoarthritis (OA) patients were co-incubated with CD14+ mononuclear cells from healthy donors without macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL). Osteoclast differentiation was evaluated via tartrate-resistant acid phosphatase (TRAP) staining and activity and F-actin ring formation. RANKL expression on synovial exosomes was assessed using flow cytometry and an enzyme-linked immunosorbent assay (ELISA). Synovial exosomes were the lowest in OA patients; these induced osteoclastogenesis in the absence of M-CSF and RANKL. Osteoclastogenesis was significantly higher with more exosomes in RA (p = 0.030) than in OA patients, but not in AS or gout patients. On treating macrophages with a specified number of synovial exosomes from RA/AS patients, exosomes induced greater osteoclastogenesis in RA than in AS patients. Synovial exosomal RANKL levels were significantly higher in RA (p = 0.035) than in AS patients. Synovial exosome numbers vary with the type of inflammatory arthritis. Synovial exosomes from RA patients may bear the disease-specific "synovial signature of osteoclastogenesis."

Patient perspectives on biological treatments for inflammatory arthritis: A multi-center study in Korea.

Objectives: The aim of this study was to evaluate the patient's perception of the use of biological disease-modifying anti-rheumatic drugs (bDMARDs) and provide a basis for physicians to understand the patient's perspective. Patients and methods: Between December 2018 and June 2019, a total of 307 patients (162 males, 145 females; mean age: 48 years; range, 18 to 81 years) were included in this investigator-initiated, multi-center, observational, and cross-sectional study in six rheumatology centers. We asked patients using bDMARDs to treat rheumatoid arthritis (RA) or ankylosing spondylitis (AS) to complete a questionnaire regarding major considerations and satisfaction with bDMARDs, preferred administration route, knowledge about bDMARDs, experiences of adverse events, non-adherence, and expectations of their healthcare provider. The satisfaction of physician and clinical information on the patient's disease and treatment were also collected. Results: Of the patients, 139 had RA and 168 had AS. Median disease duration was six years in RA and five years in AS. A total of 80.1% of the patients and 77.1% of the physicians indicated being satisfied or very satisfied with the therapeutic effect of the current bDMARD. Most patients were open to intravenous or subcutaneous injection, with the most preferred route of administration being subcutaneous (41.3%), followed by intravenous (32.0%), and oral (26.7%). The patients considered therapeutic effect to be more important than cost or convenience while choosing a bDMARD (69.3%), and most were willing to be educated about therapeutic effects (46.1%). Only 35.2% of the patients reported well and/or very well knowledge about the therapeutic effects, side effects, and administration methods of their current bDMARD, and 86.6% cited their physician as the primary source of information about biological treatment. Conclusion: Patients value therapeutic effect more than cost or convenience while selecting a bDMARD, and consider their physicians to be the primary information source. Therefore, it is important for physicians to provide appropriate education and encourage patients to cooperate actively with treatment.

CD99-PTPN12 Axis Suppresses Actin Cytoskeleton-Mediated Dimerization of Epidermal Growth Factor Receptor.

The epidermal growth factor receptor (EGFR), a member of ErbB receptor tyrosine kinase (RTK) family, is activated through growth factor-induced reorganization of the actin cytoskeleton and subsequent dimerization. We herein explored the molecular mechanism underlying the suppression of ligand-induced EGFR dimerization by CD99 agonists and its relevance to tumor growth in vivo. Epidermal growth factor (EGF) activated the formation of c-Src/focal adhesion kinase (FAK)-mediated intracellular complex and subsequently induced RhoA-and Rac1-mediated actin remodeling, resulting in EGFR dimerization and endocytosis. In contrast, CD99 agonist facilitated FAK dephosphorylation through the HRAS/ERK/PTPN12 signaling pathway, leading to inhibition of actin cytoskeletal reorganization via inactivation of the RhoA and Rac1 signaling pathways. Moreover, CD99 agonist significantly suppressed tumor growth in a BALB/c mouse model injected with MDA-MB-231 human breast cancer cells. Taken together, these results indicate that CD99-derived agonist ligand inhibits epidermal growth factor (EGF)-induced EGFR dimerization through impairment of cytoskeletal reorganization by PTPN12-dependent c-Src/FAK inactivation, thereby suppressing breast cancer growth.