1.Association of TP53 Mutation Status and Sex with Clinical Outcome in Non–Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors: A Retrospective Cohort Study
Songji CHOI ; Se Hyun KIM ; Sejoon LEE ; Jeongmin SEO ; Minsu KANG ; Eun Hee JUNG ; Sang-A KIM ; Koung Jin SUH ; Ji Yun LEE ; Ji-Won KIM ; Jin Won KIM ; Jeong-Ok LEE ; Yu Jung KIM ; Keun-Wook LEE ; Jee Hyun KIM ; Soo-Mee BANG ; Jong Seok LEE
Cancer Research and Treatment 2025;57(1):70-82
Purpose:
Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC.
Materials and Methods:
Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed.
Results:
In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT.
Conclusion
Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.
2.Association of TP53 Mutation Status and Sex with Clinical Outcome in Non–Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors: A Retrospective Cohort Study
Songji CHOI ; Se Hyun KIM ; Sejoon LEE ; Jeongmin SEO ; Minsu KANG ; Eun Hee JUNG ; Sang-A KIM ; Koung Jin SUH ; Ji Yun LEE ; Ji-Won KIM ; Jin Won KIM ; Jeong-Ok LEE ; Yu Jung KIM ; Keun-Wook LEE ; Jee Hyun KIM ; Soo-Mee BANG ; Jong Seok LEE
Cancer Research and Treatment 2025;57(1):70-82
Purpose:
Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC.
Materials and Methods:
Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed.
Results:
In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT.
Conclusion
Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.
3.Association of TP53 Mutation Status and Sex with Clinical Outcome in Non–Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors: A Retrospective Cohort Study
Songji CHOI ; Se Hyun KIM ; Sejoon LEE ; Jeongmin SEO ; Minsu KANG ; Eun Hee JUNG ; Sang-A KIM ; Koung Jin SUH ; Ji Yun LEE ; Ji-Won KIM ; Jin Won KIM ; Jeong-Ok LEE ; Yu Jung KIM ; Keun-Wook LEE ; Jee Hyun KIM ; Soo-Mee BANG ; Jong Seok LEE
Cancer Research and Treatment 2025;57(1):70-82
Purpose:
Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC.
Materials and Methods:
Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed.
Results:
In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT.
Conclusion
Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.
4.Skeletal-Related Events in Patients With Multiple Myeloma: A Comprehensive Retrospective Cohort Study
Ji Yun LEE ; Ju-Hyun LEE ; Jeongmin SEO ; Minsu KANG ; Eun Hee JUNG ; Sang-A KIM ; Koung Jin SUH ; Ji-Won KIM ; Se Hyun KIM ; Jeong-Ok LEE ; Jin Won KIM ; Yu Jung KIM ; Keun-Wook LEE ; Jee Hyun KIM ; Jong Seok LEE ; Soo-Mee BANG
Journal of Korean Medical Science 2024;39(22):e175-
Background:
Multiple myeloma (MM) patients are at risk of skeletal-related events (SREs) like spinal cord compression, pathologic fractures, bone surgery, and radiation to bone. Realworld data regarding SREs in MM are limited.
Methods:
We conducted a large, retrospective, nationwide cohort study using the Korean Health Insurance Review and Assessment Service (HIRA) database from 2007 to 2018.
Results:
Over a 12-year study period, we identified 6,717 patients who developed symptomatic MM. After a median follow-up of 35.1 months (interquartile range [IQR], 20.8–58.2 months), 43.6% of these patients experienced SREs, and 39.6% had four or more SREs. One in five patients (20.0%) experienced pathologic fractures within the first year of follow-up. The median time to first SRE was 9.6 months (IQR, 1.2–25.8 months), with 3.0 months in the group with prior SREs and 19.8 months in the group without prior SREs.During follow-up, 78.5% of patients received bisphosphonates. Multiple logistic regression analysis revealed several factors associated with an increased risk of SREs, including being female (odds ratio [OR], 1.44), aged 50 or older (OR, 1.87), having cerebrovascular disease (OR, 1.34), undergoing first-line chemotherapy regimens not containing bortezomib or lenalidomide (OR, 1.49), and being in the group with prior SREs and bisphosphonate use (OR, 5.63), compared to the group without prior SREs and without bisphosphonate use.
Conclusion
This population-based study is the first to report the incidence and risk factors of SREs in Korean MM patients, which can be used to assess their bone health.
5.Clinical Trial: Efficacy of Mosapride Controlledrelease and Nortriptyline in Patients With Functional Dyspepsia: A Multicenter, Double-placebo, Double-blinded, Randomized Controlled, Parallel Clinical Study
Chung Hyun TAE ; Ra Ri CHA ; Jung-Hwan OH ; Tae-Guen GWEON ; Jong Kyu PARK ; Ki Bae BANG ; Kyung Ho SONG ; Cheal Wung HUH ; Ju Yup LEE ; Cheol Min SHIN ; Jong Wook KIM ; Young Hoon YOUN ; Joong Goo KWON ;
Journal of Neurogastroenterology and Motility 2024;30(1):106-115
Background/Aims:
Prokinetic agents and neuromodulators are among the treatment options for functional dyspepsia (FD), but their comparative efficacy is unclear. We aimed to compare the efficacy of mosapride controlled-release (CR) and nortriptyline in patients with FD after 4 weeks of treatment.
Methods:
Participants with FD were randomly assigned (1:1) to receive mosapride CR (mosapride CR 15 mg and nortriptyline placebo) or nortriptyline (mosapride CR placebo and nortriptyline 10 mg) in double-placebo, double-blinded, randomized controlled, parallel clinical study. The primary endpoint was defined as the proportion of patients with overall dyspepsia improvement after 4 weeks treatment. The secondary endpoints were changes in individual symptom scores, anxiety, depression, and quality of life.
Results:
One hundred nine participants were recruited and assessed for eligibility, and 54 in the mosapride CR group and 50 in the nortriptyline group were included in the modified intention-to-treat protocol. The rate of overall dyspepsia improvement was similar between groups (53.7% vs 54.0%, P = 0.976). There was no difference in the efficacy of mosapride CR and nortriptyline in a subgroup analysis by FD subtype (59.3% vs 52.5% in postprandial distress syndrome, P = 0.615; 44.4% vs 40.0% in epigastric pain syndrome, P = > 0.999; 50.0% vs 59.1% in overlap, P = 0.565; respectively). Both treatments significantly improved anxiety, depression, and quality of life from baseline.
Conclusion
Mosapride CR and nortriptyline showed similar efficacy in patients with FD regardless of the subtype. Both treatments could be equally helpful for improving quality of life and psychological well-being while also relieving dyspepsia.
6.Effect of Helicobacter pylori Eradication on Body Weight: A Multicenter Propensity Score-matched Analysis in Korea
Jong Wook KIM ; Myong Ki BAEG ; Chang Seok BANG ; Jong-Kyu PARK ; Jung-Hwan OH ;
Journal of Neurogastroenterology and Motility 2023;29(3):352-359
Background/Aims:
There is growing interest in whether Helicobacter pylori eradication (HPE) can affect body weight.
Methods:
Data from 5 universities between January 2013 and December 2019 were analyzed retrospectively. H. pylori-positive subjects who had body weight measurements taken at least twice at intervals of 3 months or longer were included. Using propensity score (PS)-matched data, changes in body mass index (BMI) and the lipid profile after HPE were compared with the non-HPE group.
Results:
Among 363 eligible patients, 131 HPE patients were PS-matched to 131 non-HPE patients. The median intervals between the measurements were 610 (range, 154-1250) days and 606 (range, 154-1648) days in the HPE and non-HPE groups, respectively. In both groups, the mean BMI increased (from 24.5 kg/m2 to 24.7 kg/m2 in the HPE group, and from 24.4 kg/m2 to 24.5 kg/m2 in the non-HPE group). The 2 groups did not show significantly different changes (P = 0.921). In the lowest baseline BMI quartile, the BMI increased after HPE by 1.23 (standard deviation [SD], 3.72) kg/m2 (P = 0.060), and the non-HPE group showed a decreased BMI at the time of follow-up (by − 0.24 [SD, 5.25] kg/m2 ; P = 0.937) (between-group P = 0.214). Triglyceride levels increased after HPE (mean: 135 [SD, 78] to 153 [SD, 100] mg/dL; between-group P = 0.053).
Conclusion
The overall BMI change was not significantly different between the HPE and non-HPE groups, but patients with low BMI showed a tendency to gain weight after HPE. Triglyceride levels increased after HPE with marginal significance.
7.Modified Rectangular Loop Suture for Refractory Pupillary Optic Capture of Scleral Fixated Intraocular Lens
Sung Soo HWANG ; Ji Min KWON ; Jong Wook BANG ; Hyun Woong KIM ; Kang Yeun PAK
Journal of the Korean Ophthalmological Society 2023;64(7):598-604
Purpose:
To report a modified rectangular loop suture technique for patients with refractory pupillary optic capture after intraocular lens scleral fixation.
Methods:
A modified rectangular loop suture was performed in four patients with persistent pupillary capture despite medication and laser iridotomy. A loop suture pattern was designed in the two quadrants without the scleral fixation knot. A 2 mm loop suture point was marked 2 mm away from the corneal limbus. The suture point was similarly marked in the opposite quadrants. Small conjunctival incisions were made at a marked point and a non-absorbable 10-0 prolene long needle was passed. The needle was inserted at the 1 o’clock position through the conjunctival incision and passed between the intraocular lens and the iris plane. Then it was withdrawn using a 26-gauge (G) syringe from the 8 o’clock position in the opposite quadrant. Similarly, the needle was passed from the 7 o’clock position under the conjunctiva, and pulled out of the sclera at the 2 o’clock position. It was then passed to the 1 o’clock position under the conjunctiva and a knot was made and buried. The operation was completed without closure of the conjunctival incision.
Results:
In all four eyes, pupillary optic capture was corrected and remained stable without recurrence for an average of 7.25 months.
Conclusions
The modified rectangular loop suture may be useful for refractory pupillary capture cases. The procedure is relatively simple and minimizes scleral exposure to the conjunctival suture. It is expected that this may reduce patient discomfort.
8.Treatment Results of Treatment-naïve Neovascular Age-related Macular Degeneration in Patients Over 85 Years of Age
Ji Min KWON ; Sung Soo HWANG ; Jong Wook BANG ; Hyun Woong KIM ; Jae Wan LIM ; Sang Joon LEE ; Dong Geun KIM ; Hyun Duck KWAK ; Kang Yeun PAK
Journal of the Korean Ophthalmological Society 2023;64(9):777-783
Purpose:
To investigate the characteristics and treatment results of patients aged ≥ 85 years who were diagnosed with treatment-naïve neovascular age-related macular degeneration (nAMD).
Methods:
The medical records of patients diagnosed with treatment-naïve nAMD who were ≥ 85 years old at the time of diagnosis with at least 12 months follow-up were retrospectively reviewed. The number of intravitreal injections of anti-vascular endothelial growth factor (VEGF) and agents used during the entire period were investigated. Best-corrected visual acuity and optical coherence tomography results before and after treatment were analyzed. Visual acuity of the fellow eye was also collected.
Results:
A total of 40 eyes of 40 patients with mean age of 87.5 ± 2.4 were included in the study. The mean logarithm of the minimal angle of resolution visual acuity was 0.85 ± 0.57, and the mean of the fellow eye was 0.93 ± 0.99. Compared to before the treatment, there was no significant difference after intravitreal injection in terms of visual acuity. Central retinal thickness showed significant reduction at all time points after treatment.
Conclusions
In patients aged ≥ 85 years at the time of diagnosis, intravitreal injections of anti-VEGF prevented deterioration of visual acuity and showed successful anatomical outcomes. Especially, many had poor visual acuity in the fellow eye, suggesting the importance of maintaining visual acuity. Therefore, active treatment is necessary in the elderly.
9.Circulating Extracellular-Vesicle-Incorporated MicroRNAs as Potential Biomarkers for Ischemic Stroke in Patients With Cancer
Oh Young BANG ; Eun Hee KIM ; Mi Jeong OH ; Jaein YOO ; Gyun Sik OH ; Jong-Won CHUNG ; Woo-Keun SEO ; Gyeong-Moon KIM ; Myung-Ju AHN ; Seong Wook YANG ;
Journal of Stroke 2023;25(2):251-265
Background:
and Purpose This study aimed to evaluate whether extracellular-vesicle-incorporated microRNAs (miRNAs) are potential biomarkers for cancer-related stroke.
Methods:
This cohort study compared patients with active cancer who had embolic stroke of unknown sources (cancer-stroke group) with patients with only cancer, patients with only stroke, and healthy individuals (control groups). The expression profiles of miRNAs encapsulated in plasma exosomes and microvesicles were evaluated using microarray and validated using quantitative real-time polymerase chain reaction. The XENO-QTM miRNA assay technology was used to determine the absolute copy numbers of individual miRNAs in an external validation cohort.
Results:
This study recruited 220 patients, of which 45 had cancer-stroke, 76 were healthy controls, 39 were cancer controls, and 60 were stroke controls. Three miRNAs (miR-205-5p, miR-645, and miR-646) were specifically incorporated into microvesicles in patients with cancer-related stroke, cancer controls, and stroke controls. The area under the receiver operating characteristic curves of these three miRNAs were 0.7692–0.8510 for the differentiation of patients with cancer-stroke from cancer-controls and 0.8077–0.8846 for the differentiation of patients with cancer-stroke from stroke controls. The levels of several miRNAs were elevated in the plasma exosomes of patients with cancer, but were lower than those in plasma microvesicles. An in vivo study showed that systemic injection of miR-205-5p promoted the development of arterial thrombosis and elevation of D-dimer levels.
Conclusion
Stroke due to cancer-related coagulopathy was associated with deregulated expression of miRNAs, particularly microvesicle-incorporated miR-205-5p, miR-645, and miR-646. Further prospective studies of extracellular-vesicle-incorporated miRNAs are required to confirm the diagnostic role of miRNAs in patients with stroke and to screen the roles of miRNAs in patients with cancer.
10.Evaluation of Genetic Diversity and Population Structure Analysis among Germplasm of Agaricus bisporus by SSR Markers
Hyejin AN ; Hwa-Yong LEE ; Hyeran SHIN ; Jun Hyoung BANG ; Seahee HAN ; Youn-Lee OH ; Kab-Yeul JANG ; Hyunwoo CHO ; Tae Kyung HYUN ; Jwakyung SUNG ; Yoon-Sup SO ; Ick-Hyun JO ; Jong-Wook CHUNG
Mycobiology 2021;49(4):376-384
Agaricus bisporus is a popular edible mushroom that is cultivated worldwide. Due to its secondary homothallic nature, cultivated A. bisporus strains have low genetic diversity, and breeding novel strains is challenging. The aim of this study was to investigate the genetic diversity and population structure of globally collected A. bisporus strains using simple sequence repeat (SSR) markers. Agaricus bisporus strains were divided based on genetic distance-based groups and model-based subpopulations. The major allele frequency (MAF), number of genotypes (NG), number of alleles (NA), observed heterozygosity (HO), expected heterozygosity (HE), and polymorphic information content (PIC) were calculated, and genetic distance, population structure, genetic differentiation, and Hardy–Weinberg equilibrium (HWE) were assessed. Strains were divided into two groups by distance-based analysis and into three subpopulations by model-based analysis. Strains in subpopulations POP A and POP B were included in Group I, and strains in subpopulation POP C were included in Group II. Genetic differentiation between strains was 99%. Marker AB-gSSR-1057 in Group II and subpopulation POP C was confirmed to be in HWE. These results will enhance A. bisporus breeding programs and support the protection of genetic resources.

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