1.Clinicopathological Features and Molecular Signatures of Lateral Neck Lymph Node Metastasis in Papillary Thyroid Microcarcinoma
Jinsun LIM ; Han Sai LEE ; Jin-Hyung HEO ; Young Shin SONG
Endocrinology and Metabolism 2024;39(2):324-333
Background:
The predictive factors for lateral neck lymph node metastasis (LLNM) in papillary thyroid microcarcinoma (PTMC) remain undetermined. This study investigated the clinicopathological characteristics, transcriptomes, and tumor microenvironment in PTMC according to the LLNM status. We aimed to identify the biomarkers associated with LLNM development.
Methods:
We retrospectively reviewed the medical records of patients with PTMC from two independent institutions between 2018 and 2022 (n=597 and n=467). We compared clinicopathological features between patients without lymph node metastasis (N0) and those with LLNM (N1b). Additionally, laser capture microdissection and RNA sequencing were performed on primary tumors from both groups, including metastatic lymph nodes from the N1b group (n=30; 20 primary tumors and 10 paired LLNMs). We corroborated the findings using RNA sequencing data from 16 BRAF-like PTMCs from The Cancer Genome Atlas. Transcriptomic analyses were validated by immunohistochemical staining.
Results:
Clinicopathological characteristics, such as male sex, multifocality, extrathyroidal extension, lymphatic invasion, and central node metastasis showed associations with LLNM in PTMCs. Transcriptomic profiles between the N0 and N1b PTMC groups were similar. However, tumor microenvironment deconvolution from RNA sequencing and immunohistochemistry revealed an increased abundance of tumor-associated macrophages, particularly M2 macrophages, in the N1b group.
Conclusion
Patients with PTMC who have a male sex, multifocality, extrathyroidal extension, lymphatic invasion, and central node metastasis exhibited an elevated risk for LLNM. Furthermore, infiltration of M2 macrophages in the tumor microenvironment potentially supports tumor progression and LLNM in PTMCs.
2.Changes of Parathyroid Hormone and Vitamin D Metabolites According to Estimated Glomerular Filtration Rate in Chronic Kidney Disease Patients.
Sukyong YU ; Jinhee CHO ; Namkyu LIM ; Myounghee LEE ; Jinsun PARK ; Inwhee PARK ; Gyutae SHIN ; Heungsoo KIM
Korean Journal of Nephrology 2008;27(1):28-37
PURPOSE: Disturbances of mineral metabolism are common during the course of chronic kidney disease (CKD) and may lead to serious and debilitating complications unless properly treated. The purpose of this study is to quantify the prevalence of secondary hyperparathyroidism and vitamin D deficiency in non-dialysed chronic kidney disease 3, 4, and 5 in Korea. METHODS: This study included patients who had documented eGFR<60 mL/min/1.73m2 and non-dialysed and had not received any vitamin D compounds. eGFR was calculated by simplified MDRD (Modification of Diet in Renal Disease study) equation. Blood samples were collected for serum creatinine, calcium, phosphate, intact PTH and vitamin D metabolites between May 2006 and April 2007. RESULTS: According to K/DOQI guideline, the prevalence of hyperparathyroidism was 46.9% (15/32) in stage 3 (iPTH>70 pg/mL),45.9% (17/37) in stage 4 (iPTH>110 pg/mL) and 20.5% (9/44) in stage 5 patients (iPTH>300 pg/mL). The prevalence of 25-hydroxyvitamin D deficiency (25(OH)D3<15 ng/mL) was 86.2% (25/29) in stage 3, 75.7% (28/37) in stage 4 and 88.4% (38/43) in stage 5. There was a negative correlation between eGFR and intact PTH (r=-0.531, p=0.000) and a positive correlation between eGFR and 1,25-dihydroxyvitamin D (r=0.587, p=0.000). Conclusions: So far as non-dialysed CKD patients in Korea are concerned, quantification of the prevalence of abnormality of intact PTH and vitamin D deficiency has been described in this study. More research should be conducted in the future in a prospective, multi-center community cohort study, of which subjects include the early stages like CKD 1 and 2.
Calcium
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Cohort Studies
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Creatinine
;
Diet
;
Glomerular Filtration Rate
;
Humans
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Hyperparathyroidism
;
Hyperparathyroidism, Secondary
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Kidney Failure, Chronic
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Korea
;
Parathyroid Hormone
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Prevalence
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Renal Insufficiency, Chronic
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Vitamin D
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Vitamin D Deficiency
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Vitamins
3.Different Molecular Phenotypes of Progression in BRAF- and RAS-Like Papillary Thyroid Carcinoma
Jinsun LIM ; Han Sai LEE ; Jiyun PARK ; Kyung-Soo KIM ; Soo-Kyung KIM ; Yong-Wook CHO ; Young Shin SONG
Endocrinology and Metabolism 2023;38(4):445-454
Background:
Papillary thyroid carcinoma (PTC) can be classified into two distinct molecular subtypes, BRAF-like (BL) and RASlike (RL). However, the molecular characteristics of each subtype according to clinicopathological factors have not yet been determined. We aimed to investigate the gene signatures and tumor microenvironment according to clinicopathological factors, and to identify the mechanism of progression in BL-PTCs and RL-PTCs.
Methods:
We analyzed RNA sequencing data and corresponding clinicopathological information of 503 patients with PTC from The Cancer Genome Atlas database. We performed differentially expressed gene (DEG), Gene Ontology, and molecular pathway enrichment analyses according to clinicopathological factors in each molecular subtype. EcoTyper and CIBERSORTx were used to deconvolve the tumor cell types and their surrounding microenvironment.
Results:
Even for the same clinicopathological factors, overlapping DEGs between the two molecular subtypes were uncommon, indicating that BL-PTCs and RL-PTCs have different progression mechanisms. Genes related to the extracellular matrix were commonly upregulated in BL-PTCs with aggressive clinicopathological factors, such as old age (≥55 years), presence of extrathyroidal extension, lymph node metastasis, advanced tumor-node-metastasis (TNM) stage, and high metastasis-age-completeness of resection- invasion-size (MACIS) scores (≥6). Furthermore, in the deconvolution analysis of tumor microenvironment, cancer-associated fibroblasts were significantly enriched. In contrast, in RL-PTCs, downregulation of immune response and immunoglobulin-related genes was significantly associated with aggressive characteristics, even after adjusting for thyroiditis status.
Conclusion
The molecular phenotypes of cancer progression differed between BL-PTC and RL-PTC. In particular, extracellular matrix and cancer-associated fibroblasts, which constitute the tumor microenvironment, would play an important role in the progression of BL-PTC that accounts for the majority of advanced PTCs.
4.Clinical Features of Chronic Obstructive Pulmonary Disease with High Fractional Exhaled Nitric Oxide
Seong AHN ; Tae-Ok KIM ; Jinsun CHANG ; Hong-Joon SHIN ; Yong-Soo KWON ; Sung-Chul LIM ; Yu-Il KIM
Tuberculosis and Respiratory Diseases 2020;83(3):234-241
Background:
The fractional exhaled nitric oxide (FENO) test is useful in asthma patients. However, a few studies on its usefulness in chronic obstructive pulmonary disease (COPD) patients have been reported. We analyzed the FENO level distribution and clinical characteristics according to the FENO level in COPD patients.
Methods:
From December 2014 to June 2019, COPD patients who underwent pulmonary function and FENO tests at Chonnam National University Hospital were retrospectively evaluated for FENO, comorbidities, asthma history, blood eosinophil, and pulmonary function test. The high FENO group was defined as those with FENO level>25 parts per billion (ppb).
Results:
A total of 849 COPD patients (mean age, 70.3±9.4 years) were included. The mean forced expiratory volume at 1 second was 66.5±21.7% and the mean FENO level was 24.3±20.5 ppb. Patients with FENO ≤25 ppb were 572 (67.4%) and those with FENO >25 ppb were 277 (32.6%). Blood eosinophil percentage was significantly higher (4.2±4.8 vs. 2.7±2.5, p<0.001) in patients with the high FENO group than the low FENO group. The high FENO group revealed a significantly higher frequency of patients with blood eosinophil percentage >3% (46.9% vs. 34.8%, p=0.001) and asthma history (25.6% vs. 8.6%, p<0.001) than the lower FENO group. Asthma history, blood eosinophil percentage >3%, and positive bronchodilator response (BDR) were independent risk factors for the high FENO level (adjusted odds ratio [aOR], 3.85; p<0.001; aOR, 1.46; p=0.017; and aOR, 1.57, p=0.034, respectively) in the multivariable analysis.
Conclusion
The FENO level distribution varied in COPD patients and the mean FENO value was slightly elevated. Asthma history, eosinophil percent, and positive BDR were independent risk factors for the high FENO level.
5.Occupational Exposure to Pesticides and Lung Cancer Risk: A Propensity Score Analyses
Byungmi KIM ; Eun Young PARK ; Jinsun KIM ; Eunjung PARK ; Jin-Kyoung OH ; Min Kyung LIM
Cancer Research and Treatment 2022;54(1):130-139
Purpose:
Occupational exposure to pesticides is thought to be associated with lung cancer, but studies have yielded conflicting results. We performed a propensity score (PS) based analyses to evaluate the relationship between occupational exposure to pesticides and lung cancer risk in the Korea National Cancer Center community-based cohort study (KNCCCS).
Materials and Methods:
During the follow-up period, 123 incidental lung cancer cases were identified, of the 7,471 subjects in the final statistical analysis. Information about occupational exposure to pesticides and other factors was collected at enrollment (2003-2010). Cox proportional hazards regression analyses were conducted. Four PS-based approaches (i.e., matching, stratification, inverse probability-of-treatment weighting, and the use of the PS as a covariate) were adopted, and the results were compared. PS was obtained from the logistic regression model. Absolute standardized differences according to occupational exposure to pesticides were provided to evaluate the balance in baseline characteristics.
Results:
In the Cox proportional hazards regression model, the hazard ratio (HR) for lung cancer according to occupational exposure to pesticides was 1.82 (95% confidence interval [CI], 1.11 to 2.98). With all the propensity score matching (PSM) methods, the HRs for lung cancer based on exposure to pesticides ranged from 1.65 (95% CI, 1.04 to 2.64) (continuous term with PSM) to 2.84 (95% CI, 1.81 to 4.46) (stratification by 5 strata of the PS). The results varied slightly based on the method used, but the direction and statistical significance remained the same.
Conclusion
Our results strengthen the evidence for an association between occupational exposure to pesticides and the risk of lung cancer.
6.Review of Sarcoidosis in a Province of South Korea from 1996 to 2014.
Min Seok KIM ; Cheol Kyu PARK ; Hong Joon SHIN ; Hyeong Won SEO ; Jinsun CHANG ; Seong AHN ; Tae Ok KIM ; Jung Hwan LIM ; In Jae OH ; Yong Soo KWON ; Yu Il KIM ; Sung Chul LIM ; Young Chul KIM
Tuberculosis and Respiratory Diseases 2017;80(3):291-295
BACKGROUND: Since the introduction of endobronchial ultrasound (EBUS)–guided transbronchial needle aspiration (TBNA) of mediastinal lymph nodes, the incidence of histopathologically-confirmed sarcoidosis has increased. METHODS: The electronic medical records of Chonnam National University (CNU) Hospital and CNU Hwasun Hospital (CNUHH) were searched for confirmed cases of sarcoidosis diagnosed between 1996 and 2014. Cases were selected using a combination of clinical, radiological, and pathological evidence. Of 115 cases with the relevant disease codes, 16 cases were excluded, as they had not been confirmed pathologically or had no definitive clinical features of sarcoidosis. RESULTS: Among 99 cases of confirmed sarcoidosis, only nine patients were diagnosed with sarcoidosis before 2008; the rest were diagnosed from 2008 onward, after the introduction of EBUS-TBNA. EBUS-TBNA was used in 75.8% of patients, open surgical biopsy in 13.2%, and mediastinoscopic biopsy in 5.1%. At the time of diagnosis, 42.4% of sarcoidosis cases were at stage I, 55.6% at stage II, and 2% at stage III. Spontaneous remission of sarcoidosis was observed in 33.3% of cases, and stable disease in 37.4%; systemic steroid treatment was initiated in 23.2% of cases. Of the patients treated with systemic steroids, 69.6% showed improvement. The median duration of steroid treatment was 5 months. CONCLUSION: Following the introduction of EBUS-TBNA, the number of newly diagnosed sarcoidosis patients has increased. Clinical features of sarcoidosis were similar to those previously reported. Spontaneous remission occurred in about one-third of patients, while one-fourth of patients required systemic steroid treatment.
Biopsy
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Bronchoscopy
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Diagnosis
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Electronic Health Records
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Endoscopic Ultrasound-Guided Fine Needle Aspiration
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Humans
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Incidence
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Jeollanam-do
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Korea*
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Lymph Nodes
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Needles
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Remission, Spontaneous
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Sarcoidosis*
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Steroids
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Ultrasonography