1.p27 Cell Cycle Inhibitor and Survival in Luminal-Type Breast Cancer:Gene Ontology, Machine Learning, and Drug Screening Analysis
In Ah PARK ; Yung-Kyun NOH ; Kyueng-Whan MIN ; Dong-Hoon KIM ; Jeong-Yeon LEE ; Byoung Kwan SON ; Mi Jung KWON ; Myung-Hoon HAN ; Joon Young HUR ; Jung Soo PYO
Journal of Breast Cancer 2024;27(5):305-322
Purpose:
A widely distributed cell cycle inhibitor, p27, regulates cyclin-dependent kinase-cyclin complexes. Although the prognostic value of p27 has been established for various types of carcinomas, its role in luminal breast cancer remains poorly understood. This study aimed to explore the functional enrichment of p27 and identify potential drug targets in patients with luminal-type breast cancer.
Methods:
Clinicopathological data were collected from 868 patients with luminal-type breast cancer. Additionally, publicly available data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (1,500 patients) and the Gene Expression Omnibus database (855 patients) were included in the analysis. Immunohistochemical staining for p27, differential gene expression analysis, disease ontology analysis, survival prediction modeling using machine learning (ML), and in vitro drug screening were also performed.
Results:
Low p27 expression correlated with younger age, advanced tumor stage, estrogen receptor/progesterone receptor negativity, decreased cluster of differentiation 8+ T cell count, and poorer survival outcomes in luminal-type breast cancer. The METABRIC data revealed that reduced cyclin-dependent kinase inhibitor 1B (CDKN1B) expression (encoding p27) was associated with cell proliferation-related pathways and epigenetic polycomb repressive complex 2. Using ML, p27 emerged as the second most significant survival factor after N stage, thereby enhancing survival model performance. Additionally, luminal-type breast cancer cell lines with low CDKN1B expression demonstrated increased sensitivity to specific anticancer drugs such as voxtalisib and serdemetan, implying a potential therapeutic synergy between CDKN1B-targeted approaches and these drugs.
Conclusion
The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer.
2.p27 Cell Cycle Inhibitor and Survival in Luminal-Type Breast Cancer:Gene Ontology, Machine Learning, and Drug Screening Analysis
In Ah PARK ; Yung-Kyun NOH ; Kyueng-Whan MIN ; Dong-Hoon KIM ; Jeong-Yeon LEE ; Byoung Kwan SON ; Mi Jung KWON ; Myung-Hoon HAN ; Joon Young HUR ; Jung Soo PYO
Journal of Breast Cancer 2024;27(5):305-322
Purpose:
A widely distributed cell cycle inhibitor, p27, regulates cyclin-dependent kinase-cyclin complexes. Although the prognostic value of p27 has been established for various types of carcinomas, its role in luminal breast cancer remains poorly understood. This study aimed to explore the functional enrichment of p27 and identify potential drug targets in patients with luminal-type breast cancer.
Methods:
Clinicopathological data were collected from 868 patients with luminal-type breast cancer. Additionally, publicly available data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (1,500 patients) and the Gene Expression Omnibus database (855 patients) were included in the analysis. Immunohistochemical staining for p27, differential gene expression analysis, disease ontology analysis, survival prediction modeling using machine learning (ML), and in vitro drug screening were also performed.
Results:
Low p27 expression correlated with younger age, advanced tumor stage, estrogen receptor/progesterone receptor negativity, decreased cluster of differentiation 8+ T cell count, and poorer survival outcomes in luminal-type breast cancer. The METABRIC data revealed that reduced cyclin-dependent kinase inhibitor 1B (CDKN1B) expression (encoding p27) was associated with cell proliferation-related pathways and epigenetic polycomb repressive complex 2. Using ML, p27 emerged as the second most significant survival factor after N stage, thereby enhancing survival model performance. Additionally, luminal-type breast cancer cell lines with low CDKN1B expression demonstrated increased sensitivity to specific anticancer drugs such as voxtalisib and serdemetan, implying a potential therapeutic synergy between CDKN1B-targeted approaches and these drugs.
Conclusion
The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer.
3.JAK2 Loss Arising From Tumor-SpreadThrough-Air-Spaces (STAS) Promotes Tumor Progression by Suppressing CD8+ T Cells in Lung Adenocarcinoma:A Machine Learning Approach
Soohwan CHOI ; Hyung Suk KIM ; Kyueng-Whan MIN ; Yung-Kyun NOH ; Jeong-Yeon LEE ; Ji-Yong MOON ; Un Suk JUNG ; Mi Jung KWON ; Dong-Hoon KIM ; Byoung Kwan SON ; Jung Soo PYO ; Sun Kyun RO
Journal of Korean Medical Science 2024;39(2):e16-
Background:
Tumor spread through air spaces (STAS) is a recently discovered risk factor for lung adenocarcinoma (LUAD). The aim of this study was to investigate specific genetic alterations and anticancer immune responses related to STAS. By using a machine learning algorithm and drug screening in lung cancer cell lines, we analyzed the effect of Janus kinase 2 (JAK2) on the survival of patients with LUAD and possible drug candidates.
Methods:
This study included 566 patients with LUAD corresponding to clinicopathological and genetic data. For analyses of LUAD, we applied gene set enrichment analysis (GSEA), in silico cytometry, pathway network analysis, in vitro drug screening, and gradient boosting machine (GBM) analysis.
Results:
The patients with STAS had a shorter survival time than those without STAS (P < 0.001). We detected gene set-related downregulation of JAK2 associated with STAS using GSEA. Low JAK2 expression was related to poor prognosis and a low CD8+ T-cell fraction. In GBM, JAK2 showed improved survival prediction performance when it was added to other parameters (T stage, N stage, lymphovascular invasion, pleural invasion, tumor size). In drug screening, mirin, CCT007093, dihydroretenone, and ABT737 suppressed the growth of lung cancer cell lines with low JAK2 expression.
Conclusion
In LUAD, low JAK2 expression linked to the presence of STAS might serve as an unfavorable prognostic factor. A relationship between JAK2 and CD8+ T cells suggests that STAS is indirectly related to the anticancer immune response. These results may contribute to the design of future experimental research and drug development programs for LUAD with STAS.
4.Local ablation for hepatocellular carcinoma: 2024 expert consensus-based practical recommendation of the Korean Liver Cancer Association
Seungchul HAN ; Pil Soo SUNG ; Soo Young PARK ; Jin Woong KIM ; Hyun Pyo HONG ; Jung-Hee YOON ; Dong Jin CHUNG ; Joon Ho KWON ; Sanghyeok LIM ; Jae Hyun KIM ; Seung Kak SHIN ; Tae Hyung KIM ; Dong Ho LEE ; Jong Young CHOI ;
Journal of Liver Cancer 2024;24(2):131-144
Local ablation for hepatocellular carcinoma (HCC), a non-surgical option that directly targets and destroys tumor cells, has advanced significantly since the 1990s. Therapies with different energy sources, such as radiofrequency ablation, microwave ablation, and cryoablation, employ different mechanisms to induce tumor necrosis. The precision, safety, and effectiveness of these therapies have increased with advances in guiding technologies and device improvements. Consequently, local ablation has become the firstline treatment for early-stage HCC. The lack of organized evidence and expert opinions regarding patient selection, pre-procedure preparation, procedural methods, swift post-treatment evaluation, and follow-up has resulted in clinicians following varied practices. Therefore, an expert consensus-based practical recommendation for local ablation was developed by a group of experts in radiology and hepatology from the Research Committee of the Korean Liver Cancer Association in collaboration with the Korean Society of Image-guided Tumor Ablation to provide useful information and guidance for performing local ablation and for the pre- and posttreatment management of patients.
5.Risk of mortality and cause of death according to kidney function parameters: a nationwide observational study in Korea
Sehyun JUNG ; Soojin LEE ; Yaerim KIM ; Semin CHO ; Hyuk HUH ; Yong Chul KIM ; Seung Seok HAN ; Hajeong LEE ; Jung Pyo LEE ; Kwon Wook JOO ; Chun Soo LIM ; Yon Su KIM ; Dong Ki KIM ; Kyungdo HAN ; Sehoon PARK
Kidney Research and Clinical Practice 2024;43(2):202-215
Further study is warranted to determine the association between estimated glomerular filtration rate (eGFR) or albuminuria and the risk of death from diverse causes. Methods: We screened >10 million general health screening examinees who received health examinations conducted in 2009 using the claims database of Korea. After the exclusion of those previously diagnosed with renal failure and those with missing data, 9,917,838 individuals with available baseline kidney function measurements were included. The primary outcome was mortality and cause-specific death between 2009 and 2019 identified through death certificates based on the diagnostic codes of International Classification of Diseases, 10th revision. Multivariable Cox regression analysis adjusted for various clinicodemographic and social characteristics was used to assess mortality risk. Results: The hazard ratio of death was significantly high in both the eGFR <60 mL/min/1.73 m2 and in the eGFR ≥120 mL/ min/1.73 m2 groups in univariable and multivariable regression analyses when compared to those within the reference range (eGFR of 90–120 mL/min/1.73 m2). The results were similar for death by cardiovascular, cancer, infection, endocrine, respiratory, and digestive causes. We also found that albuminuria was associated with higher risk of death regardless of eGFR range, and those in the higher categories of dipstick albuminuria showed higher risk. Conclusion: We reconfirmed the significant association between eGFR, albuminuria, and mortality. Healthcare providers should keep in mind that albuminuria and decreased eGFR as well as kidney hyperfiltration are independent predictors of mortality.
6.Local Ablation for Hepatocellular Carcinoma: 2024Expert Consensus-Based Practical Recommendations of the Korean Liver Cancer Association
Seungchul HAN ; Pil Soo SUNG ; Soo Young PARK ; Jin Woong KIM ; Hyun Pyo HONG ; Jung-Hee YOON ; Dong Jin CHUNG ; Joon Ho KWON ; Sanghyeok LIM ; Jae Hyun KIM ; Seung Kak SHIN ; Tae Hyung KIM ; Dong Ho LEE ; Jong Young CHOI ; Research Committee of the Korean Liver Cancer Association
Korean Journal of Radiology 2024;25(9):773-787
Local ablation for hepatocellular carcinoma (HCC), a non-surgical option that directly targets and destroys tumor cells, has advanced significantly since the 1990s. Therapies with different energy sources, such as radiofrequency ablation, microwave ablation, and cryoablation, employ different mechanisms to induce tumor necrosis. The precision, safety, and effectiveness of these therapies have increased with advances in guiding technologies and device improvements. Consequently, local ablation has become the first-line treatment for early-stage HCC. The lack of organized evidence and expert opinions regarding patient selection, pre-procedure preparation, procedural methods, swift post-treatment evaluation, and follow-up has resulted in clinicians following varied practices. Therefore, an expert consensus-based practical recommendation for local ablation was developed by a group of experts in radiology and hepatology from the Research Committee of the Korean Liver Cancer Association in collaboration with the Korean Society of Image-guided Tumor Ablation to provide useful information and guidance for performing local ablation and for the pre- and post-treatment management of patients.
7.Clinical performance of implant-assisted removable partial dentures using implant surveyed crowns: a systematic review and meta-analysis
So-Yeun KIM ; Young-Eun CHO ; Seoung-Jin HONG ; Jung-Bo HUH ; Se-Wook PYO ; Yuseung YI ; Soo-Yeon YOO
The Journal of Advanced Prosthodontics 2024;16(4):255-266
PURPOSE:
This study aimed to evaluate the clinical performance of implant-assisted removable partial dentures (IARPD) with surveyed crowns, also known as implant-crown-retained removable partial dentures (ICRPDs).
MATERIALS AND METHODS:
Electronic searches of MEDLINE/PubMed, the Cochrane Central Register of Controlled Trials, the Web of Science, and the Korea Citation Index were performed according to the established search terms for ICRPD. A literature search was conducted for studies published in English or Korean until September 2023, using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines.
RESULTS:
A total of 216 journals were searched, and 31 eligible studies were selected based on the inclusion and exclusion criteria. One systematic review included five case reports of ICRPD. Nine retrospective studies evaluated implant survival/success rate, implant failure cases, marginal bone loss, periodontal status, clinical complications, and patient satisfaction. Twenty-one case reports published in Korea showed good prognoses.
CONCLUSION
According to the findings of this systematic review, ICRPD has a reasonable survival/success rate, minimal bone loss, and high patient satisfaction.
8.Overlap syndrome of systemic sclerosis with antineutrophil cytoplasmic antibody-associated vasculitis according to 2022 ACR/EULAR criteria
Jang Woo HA ; Jung Yoon PYO ; Sung Soo AHN ; Jason Jungsik SONG ; Yong-Beom PARK ; Sang-Won LEE
The Korean Journal of Internal Medicine 2024;39(3):524-536
Background/Aims:
This study applied the 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) criteria for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) to patients with systemic sclerosis (SSc) and investigated the frequency of overlap syndrome of SSc and AAV (SSc-AAV-OS).
Methods:
Among the 232 patients diagnosed with SSc, 105 with signs suggestive of small- or medium-vessel vasculitis, which were defined as the present of interstitial lung disease (ILD), peripheral neuropathy, or suspected renal vasculitis, were included in this study and analyzed.
Results:
Among the 105 SSc patients, the detection rate of ANCA was 19.0%. When the 2022 ACR/EULAR criteria were applied, the frequency of SSc-AAV-OS was 20.0%, which was much higher than 1.7% reported with previous criteria for AAV. ANCA positivity contributed to the reclassification of SSc-AAV-OS more than ANCA negativity in SSc patients with signs suggestive of small- or medium-vessel vasculitis.
Conclusions
The frequency of SSc-AAV-OS in SSc patients with signs suggestive of small- or medium-vessel vasculitis at diagnosis was 20.0%. Therefore, we suggest that physicians should perform ANCA tests in SSc patients exhibiting signs suggestive of small- or medium-vessel vasculitis and apply the new criteria for AAV.
9.p27 Cell Cycle Inhibitor and Survival in Luminal-Type Breast Cancer:Gene Ontology, Machine Learning, and Drug Screening Analysis
In Ah PARK ; Yung-Kyun NOH ; Kyueng-Whan MIN ; Dong-Hoon KIM ; Jeong-Yeon LEE ; Byoung Kwan SON ; Mi Jung KWON ; Myung-Hoon HAN ; Joon Young HUR ; Jung Soo PYO
Journal of Breast Cancer 2024;27(5):305-322
Purpose:
A widely distributed cell cycle inhibitor, p27, regulates cyclin-dependent kinase-cyclin complexes. Although the prognostic value of p27 has been established for various types of carcinomas, its role in luminal breast cancer remains poorly understood. This study aimed to explore the functional enrichment of p27 and identify potential drug targets in patients with luminal-type breast cancer.
Methods:
Clinicopathological data were collected from 868 patients with luminal-type breast cancer. Additionally, publicly available data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (1,500 patients) and the Gene Expression Omnibus database (855 patients) were included in the analysis. Immunohistochemical staining for p27, differential gene expression analysis, disease ontology analysis, survival prediction modeling using machine learning (ML), and in vitro drug screening were also performed.
Results:
Low p27 expression correlated with younger age, advanced tumor stage, estrogen receptor/progesterone receptor negativity, decreased cluster of differentiation 8+ T cell count, and poorer survival outcomes in luminal-type breast cancer. The METABRIC data revealed that reduced cyclin-dependent kinase inhibitor 1B (CDKN1B) expression (encoding p27) was associated with cell proliferation-related pathways and epigenetic polycomb repressive complex 2. Using ML, p27 emerged as the second most significant survival factor after N stage, thereby enhancing survival model performance. Additionally, luminal-type breast cancer cell lines with low CDKN1B expression demonstrated increased sensitivity to specific anticancer drugs such as voxtalisib and serdemetan, implying a potential therapeutic synergy between CDKN1B-targeted approaches and these drugs.
Conclusion
The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer.
10.Colon cancer: the 2023 Korean clinical practice guidelines for diagnosis and treatment
Hyo Seon RYU ; Hyun Jung KIM ; Woong Bae JI ; Byung Chang KIM ; Ji Hun KIM ; Sung Kyung MOON ; Sung Il KANG ; Han Deok KWAK ; Eun Sun KIM ; Chang Hyun KIM ; Tae Hyung KIM ; Gyoung Tae NOH ; Byung-Soo PARK ; Hyeung-Min PARK ; Jeong Mo BAE ; Jung Hoon BAE ; Ni Eun SEO ; Chang Hoon SONG ; Mi Sun AHN ; Jae Seon EO ; Young Chul YOON ; Joon-Kee YOON ; Kyung Ha LEE ; Kyung Hee LEE ; Kil-Yong LEE ; Myung Su LEE ; Sung Hak LEE ; Jong Min LEE ; Ji Eun LEE ; Han Hee LEE ; Myong Hoon IHN ; Je-Ho JANG ; Sun Kyung JEON ; Kum Ju CHAE ; Jin-Ho CHOI ; Dae Hee PYO ; Gi Won HA ; Kyung Su HAN ; Young Ki HONG ; Chang Won HONG ; Jung-Myun KWAK ;
Annals of Coloproctology 2024;40(2):89-113
Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients’ values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

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