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  • Wiley  (11)
  • Park, Jae Yong  (11)
  • 2020-2024  (11)
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  • Wiley  (11)
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  • 2020-2024  (11)
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  • 1
    Online Resource
    Online Resource
    Genetic variants in key necroptosis regulators predict prognosis of non‐small cell lung cancer after surgical resection
    Wiley ; 2023
    In:  Thoracic Cancer Vol. 14, No. 26 ( 2023-09), p. 2678-2686
    Details
    In: Thoracic Cancer, Wiley, Vol. 14, No. 26 ( 2023-09), p. 2678-2686
    Abstract: Necroptosis is a regulated inflammatory cell death which plays a significant role in cancer development and progression. In this study, we evaluated whether genetic variants in key regulators of necroptosis may affect survival outcome of non‐small cell lung cancer (NSCLC) patients after surgical resection. Methods A total of 674 patients who underwent curative surgery were included. Fifteen genetic variants in key regulators of necroptosis (RIPK1, RIPK3, and MLKL) were selected. The association of these variants with survival outcomes was evaluated. Results Two variants, RIPK1 rs17548629C  〉  T and MLKL rs877375G  〉  C, were associated with better overall survival and disease‐free survival in multivariate analyses. When the patients were divided according to histology, the associations were significant only in adenocarcinoma, but not in squamous cell carcinoma. RIPK1 rs17548629 C‐to‐T change was associated with significantly increased luciferase activity by modulating the binding of miR‐642a. Promoter assays showed a significantly increased promoter activity in MLKL rs877375C allele compared to G allele. Consistently, the mRNA expression level of RIPK1 and MLKL showed significant positive correlation with RIPK1 rs17548629C‐to‐T and MLKL rs877375G‐to‐C changes. Conclusion Two genetic variants in key regulators in necroptosis, RIPK1 rs17548629C  〉  T and MLKL rs877375G  〉  C, may be used as biomarkers to predict survival outcomes in surgically resected NSCLC patients.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    URL: Article
    DOI: 10.1111/tca.v14.26
    DOI: 10.1111/1759-7714.15054
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2559245-2
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  • 2
    Online Resource
    Online Resource
    Genetic variants of NEUROD1 target genes are associated with clinical outcomes of small‐cell lung cancer patients
    Wiley ; 2023
    In:  Thoracic Cancer Vol. 14, No. 13 ( 2023-05), p. 1145-1152
    Details
    In: Thoracic Cancer, Wiley, Vol. 14, No. 13 ( 2023-05), p. 1145-1152
    Abstract: Neurogenic differentiation factor 1 (NEUROD1) is frequently overexpressed in small‐cell lung cancer (SCLC). NEUROD1 plays an important role in promoting malignant behavior and survival. Methods In this study, we evaluated the association between putative functional polymorphisms in 45 NEUROD1 target genes and chemotherapy response and survival outcomes in 261 patients with SCLC. Among the 100 single nucleotide polymorphisms (SNPs) studied, two were significantly associated with both chemotherapy response and overall survival (OS) of patients with SCLC. Results The SNP rs3806915C 〉 A in semaphorin 6A ( SEMA6A ) gene was significantly associated with better chemotherapy response and OS ( p  = 0.04 and p  = 0.04, respectively). The SNP rs11265375C 〉 T in nescient helix–loop helix 1 ( NHLH1 ) gene was also associated with better chemotherapy response and OS ( p  = 0.04 and p  = 0.02, respectively). Luciferase assay showed a significantly higher promoter activity of SEMA6A with the rs3806915 A allele than C allele in H446 lung cancer cells ( p  = 4 × 10 −6 ). The promoter activity of NHLH1 showed a significantly higher with the rs11265375 T allele than C allele ( p  = 0.001). Conclusion These results suggest that SEMA6A rs3806915C 〉 A and NHLH1 rs11265375C 〉 T polymorphisms affect the promoter activity and expression of the genes, which may affect the survival outcome of patients with SCLC.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    URL: Article
    DOI: 10.1111/tca.v14.13
    DOI: 10.1111/1759-7714.14839
    Language: English
    Publisher: Wiley
    Publication Date: 2023
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  • 3
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    Prognostic significance of genetic variants in GLUT1 in stage III non‐small cell lung cancer treated with radiotherapy
    Wiley ; 2021
    In:  Thoracic Cancer Vol. 12, No. 6 ( 2021-03), p. 874-879
    Details
    In: Thoracic Cancer, Wiley, Vol. 12, No. 6 ( 2021-03), p. 874-879
    Abstract: To examine the impact of polymorphisms of glucose transporter 1 ( GLUT1 ) gene on the prognosis of patients with stage III non‐small cell lung cancer (NSCLC) who received radiotherapy. Methods Five single nucleotide polymorphisms (SNPs) (rs4658C 〉 G, rs1385129G 〉 A, rs3820589A 〉 T, rs3806401A 〉 C and rs3806400C 〉 T) in GLUT1 gene were evaluated in 90 patients with pathologically confirmed stage III NSCLC. A total of 21 patients were treated with radiotherapy alone, 25 with sequential chemoradiotherapy, and 44 with concurrent chemoradiotherapy. The association of the genetic variations of five SNPs with overall survival (OS) and progression‐free survival (PFS) was analyzed. Results Two SNPs (rs1385129 and rs3806401) were significant risk factors for OS. Three SNPs (rs1385129, rs3820589 and rs3806401) were in linkage disequilibrium. In Cox proportional hazard models, GAA haplotype was a good prognostic factor for OS (hazard ratio [HR] = 0.57, 95% confidence interval [CI] : 0.39–0.81, p = 0.002) and PFS (HR = 0.68, 95% CI: 0.47–0.99, p = 0.043), compared to variant haplotypes. The GAA/GAA diplotype was observed in 46.7% of patients; these patients showed significantly better OS (HR = 0.38, 95% CI: 0.22–0.65, p   〈  0.001) and PFS (HR = 0.51, 95% CI: 0.31–0.85, p = 0.009) compared to those with other diplotypes. Conclusions These results suggest that polymorphisms of GLUT1 gene could be used as a prognostic marker for patients with stage III NSCLC treated with radiotherapy.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    URL: Article
    DOI: 10.1111/tca.v12.6
    DOI: 10.1111/1759-7714.13851
    Language: English
    Publisher: Wiley
    Publication Date: 2021
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  • 4
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    Online Resource
    Genetic variants in LKB1 / AMPK / mTOR pathway are associated with clinical outcomes of chemotherapy in non‐small cell lung cancer
    Wiley ; 2022
    In:  Thoracic Cancer Vol. 13, No. 23 ( 2022-12), p. 3322-3330
    Details
    In: Thoracic Cancer, Wiley, Vol. 13, No. 23 ( 2022-12), p. 3322-3330
    Abstract: This study was conducted to investigate the relationship between genetic variants in LKB1/AMPK/mTOR pathway and treatment outcomes of patients with non‐small cell lung cancer (NSCLC) treated with chemotherapy. A total of 379 patients with NSCLC who underwent first‐line paclitaxel‐cisplatin chemotherapy was enrolled. The associations between 19 single nucleotide variants (SNVs) in the LKB1/AMPK/mTOR pathway and the chemotherapy response and overall survival (OS) were analyzed. Among the SNVs analyzed, AKT1 rs2494750G 〉 C and TSC1 rs2809244C 〉 A were associated with clinical outcomes after chemotherapy in multivariate analyses. The AKT1 rs2494750G 〉 C was significantly associated with a better response to chemotherapy (adjusted odds ratio [aOR]: 1.92, 95% confidence interval [CI] : 1.02–3.62, p  = 0.04). The TSC1 rs2809244C 〉 A were significantly associated with better OS (adjusted hazard ratio [aHR]: 0.79, 95% CI: 0.62–0.99, p  = 0.04). When stratified by tumor histology, AKT1 rs2494750G 〉 C exhibited a significant association with the chemotherapy response only in adenocarcinoma and TSC1 rs2809244C 〉 A was also significantly associated with OS only in adenocarcinoma. This result suggests that the AKT1 rs2494750G 〉 C and TSC1 rs2809244 C 〉 A may be useful for predicting the clinical outcome of first‐line paclitaxel‐cisplatin chemotherapy in NSCLC.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    URL: Article
    DOI: 10.1111/tca.v13.23
    DOI: 10.1111/1759-7714.14688
    Language: English
    Publisher: Wiley
    Publication Date: 2022
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  • 5
    Online Resource
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    Clinical implication of minimal presence of solid or micropapillary subtype in early‐stage lung adenocarcinoma
    Wiley ; 2021
    In:  Thoracic Cancer Vol. 12, No. 2 ( 2021-01), p. 235-244
    Details
    In: Thoracic Cancer, Wiley, Vol. 12, No. 2 ( 2021-01), p. 235-244
    Abstract: We investigated the clinical features and surgical outcomes of lung adenocarcinoma with minimal solid or micropapillary (S/MP) components, with a focus on stage IA. Methods We enrolled 506 patients with lung adenocarcinoma who underwent curative resection in this study. Clinical features and surgical outcomes were compared between the groups with and without the S/MP subtype (S/MP+ and S/MP−, respectively), and between the group with an S/MP proportion of ≤5% (S/MP5) and the S/MP−. Results The S/MP subtype was present in 247 patients (48.8%); 129 (25.5%) were grouped as the S/MP5 group. The S/MP+ and S/MP5 groups had larger tumors, higher frequency of lymph node metastasis, and more advanced stages of disease than the S/MP− group ( P   〈  0.001, all comparisons). Pleural, lymphatic, and vascular invasions occurred more frequently in the S/MP+ and S/MP5 groups ( P   〈  0.001, all comparisons for S/MP+ vs. S/MP−; P  ≤ 0.01, all comparisons for S/MP5 vs. S/MP−). The S/MP+ and S/MP5 groups showed a shorter time to recurrence and cancer‐related death than the S/MP− group( P   〈  0.001, both comparisons). For stage I, the presence or absence of the S/MP subtype defined prognostic subgroups better than the stage IA/IB classification. Notably, in the multivariate analysis, the minimal S/MP component was a significant predictor of recurrence, even in stage IA. Conclusions The presence of the minimal S/MP component was a significant predictor of poor prognosis after surgery, even in stage IA patients. Clinical trials to evaluate the advantages of adjuvant chemotherapy for this subset of patients and further investigations to understand underlying biological mechanisms of poor prognosis are needed. Key points Significant findings of the study: We demonstrated that only minimal presence of solid or micropapillary component was profoundly associated with aggressive clinicopathological features and poor prognosis after complete resection even in stage IA lung adenocarcinoma. What this study adds: Our results suggest that minimal presence of these subtypes is a strong prognostic factor which should be taken into account in the risk assessment for adjuvant chemotherapy in lung adenocarcinoma.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    URL: Article
    DOI: 10.1111/tca.v12.2
    DOI: 10.1111/1759-7714.13754
    Language: English
    Publisher: Wiley
    Publication Date: 2021
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  • 6
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    Epigenetic and genetic inactivation of tumor suppressor miR ‐135a in non‐small‐cell lung cancer
    Wiley ; 2023
    In:  Thoracic Cancer Vol. 14, No. 11 ( 2023-04), p. 1012-1020
    Details
    In: Thoracic Cancer, Wiley, Vol. 14, No. 11 ( 2023-04), p. 1012-1020
    Abstract: Despite therapeutic advances, lung cancer prognosis remains poor. Loss of heterozygosity (LOH) in the 3p21 region is well documented in lung cancer, but the specific causative genes have not been identified. Materials and Methods Here, we aimed to examine the clinical impact of miR‐135a , located in the 3p21 region, in lung cancer. miR‐135a expression was assessed using quantitative real‐time polymerase chain reaction. LOH was analyzed at microsatellite loci D3S1076 and D3S1478, and promoter methylation status was determined by pyrosequencing of resected samples of primary non‐small‐cell lung cancer (NSCLC). The regulation of telomerase reverse transcriptase (TERT) was evaluated in lung cancer cells H1299 by luciferase report assays after treatment with miR‐135a mimics. Results miR‐135a was significantly downregulated in squamous cell cancer (SCC) tumor tissues compared to normal tissues ( p  = 0.001). Low miR‐135a expression was more frequent in patients with SCC ( p  = 2.9 × 10 −4 ) and smokers ( p  = 0.01). LOH and hypermethylation were detected in 27.8% (37/133) and 17.3% (23/133) of the tumors, respectively. Overall, 36.8% (49/133) of the NSCLC cases harbored either miR‐135a LOH or promoter hypermethylation. The frequencies of LOH and hypermethylation were significantly associated with SCCs ( p  = 2 × 10 −4 ) and late‐stage ( p  = 0.04), respectively. MiR‐135a inhibited the relative luciferase activity of psiCHECK2‐ TERT ‐3'UTR. Conclusion These results suggest that miR‐135a may act as a tumor suppressor to play an important role in lung cancer carcinogenesis, which will provide a new insight into the translational value of miR‐135a . Further large‐scale studies are required to confirm these findings.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    URL: Article
    DOI: 10.1111/tca.v14.11
    DOI: 10.1111/1759-7714.14838
    Language: English
    Publisher: Wiley
    Publication Date: 2023
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  • 7
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    Menopausal hormone therapy and the risk of cataracts in postmenopausal women in South Korea
    Wiley ; 2023
    In:  Ophthalmic and Physiological Optics Vol. 43, No. 2 ( 2023-03), p. 254-262
    Details
    In: Ophthalmic and Physiological Optics, Wiley, Vol. 43, No. 2 ( 2023-03), p. 254-262
    Abstract: Postmenopausal women have a higher prevalence of cataracts than men of a similar age. This study aimed to evaluate the effects of menopausal hormone therapy (MHT) on lens opacities in postmenopausal women. Methods This retrospective cohort study analysed population‐based health insurance data in South Korea collected from 2002 to 2019. To determine the risk factors associated with cataract, postmenopausal women ( N  = 2,506,271) were grouped according to post‐MHT use. The treatment group was further divided into the following subgroups: tibolone, combined oestrogen plus progestin by manufacturer, oral oestrogen, combined oestrogen plus progestin by physician and topical oestrogen groups. The main outcome measure was the prevalence of cataracts. Results The control group comprised 463,151 postmenopausal women who had never used MHT after menopause, while the treatment group included 228,033 postmenopausal women who had used MHT continuously for at least 6 months. The treatment group had a higher incidence of cataracts than the control group based on Cox proportional hazards ratio analysis. Low socioeconomic status and high parity were identified as risk factors for cataracts, and reduced risk of cataracts was associated with living in rural areas and drinking alcohol. Conclusions Women undergoing post‐MHT, including tibolone, had a higher incidence of cataracts. Cataract development should be a concern when examining postmenopausal patients using MHT.
    Type of Medium: Online Resource
    ISSN: 0275-5408 , 1475-1313
    URL: Issue
    URL: Article
    DOI: 10.1111/opo.v43.2
    DOI: 10.1111/opo.13089
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2008422-5
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  • 8
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    Polymorphism in ASCL1 target gene DDC is associated with clinical outcomes of small cell lung cancer patients
    Wiley ; 2020
    In:  Thoracic Cancer Vol. 11, No. 1 ( 2020-01), p. 19-28
    Details
    In: Thoracic Cancer, Wiley, Vol. 11, No. 1 ( 2020-01), p. 19-28
    Abstract: Achaete‐scute homolog 1 (ASCL1) is a basic helix‐loop‐helix transcription factor and is essential in the differentiation of neuroendocrine cells and neural tissues. ASCL1 is frequently overexpressed in small cell lung cancer (SCLC) and plays a crucial role in the pathogenesis of SCLC. Methods This study was conducted to identify the association between single nucleotide polymorphisms (SNPs) in ASCL1 target genes and clinical outcomes of patients with SCLC after chemotherapy. A total of 261 patients diagnosed with SCLC were enrolled in this study. The association between 103 SNPs in 58 ASCL1 target genes and the response to chemotherapy and survival of patients with SCLC were analyzed. Results Among the 103 SNPs, 10 SNPs were significantly associated with the response to chemotherapy, and 19 SNPs were associated with OS in multivariate analyses. Among these, Dopa Decarboxylase (DDC) rs12666409A 〉 T was significantly associated with both a worse response to chemotherapy and worse OS (adjusted odds ratio [aOR] = 0.40, 95% CI = 0.18–0.90, P = 0.03; adjusted hazard ratio [aHR] = 1.52, 95% CI = 1.10–2.10, P = 0.01, respectively, under a dominant model). In a stage‐stratified analysis, the association was significant only in the extensive disease subgroup (aOR = 0.19, 95% CI = 0.06–0.60, P = 0.01; aHR = 1.73, 95% CI = 1.16–2.56, P = 0.01, respectively, under a dominant model), but not in the limited disease subgroup. Conclusion The results of our study suggest that DDC rs12666409A 〉 T may be useful markers for predicting the clinical outcomes of patients with SCLC undergoing chemotherapy.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    URL: Article
    DOI: 10.1111/tca.v11.1
    DOI: 10.1111/1759-7714.13212
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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  • 9
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    Effect of genetic variation in Notch regulator DTX1 on SCLC prognosis compared with the effect on NSCLC prongosis
    Wiley ; 2020
    In:  Thoracic Cancer Vol. 11, No. 9 ( 2020-09), p. 2698-2703
    Details
    In: Thoracic Cancer, Wiley, Vol. 11, No. 9 ( 2020-09), p. 2698-2703
    Abstract: Deltex‐1 (DTX1) is a negative regulator of the Notch signaling pathway. Here, we investigated the clinical effect of DTX1 rs1732786A  〉  G, which is associated with better prognosis in patients with early‐stage non‐small cell lung cancer (NSCLC), in 261 patients with small cell lung cancer (SCLC). DTX1 rs1732786A  〉  G was associated with a significantly worse chemotherapy response and lower overall survival in the codominant model (odds ratio = 0.42, 95% confidence interval [CI]: 0.26–0.66, P = 2 × 10 −4 ; hazard ratio = 1.47, 95% CI: 1.17–1.84, P = 0.001, respectively). An in vitro luciferase assay was performed, and the 1732786G allele demonstrated significantly higher promoter activity than the 1732786A allele ( P = 2 × 10 −7 ). In summary, DTX1 rs1732786A  〉  G was associated with poor prognosis in patients with SCLC as opposed to patients with NSCLC. Key points Significant findings of the study DTX1 rs1732786A  〉  G was associated with better prognosis in patients with early‐stage non‐small cell lung cancer (NSCLC) in our previous study. What this study adds DTX1 rs1732786A  〉  G was associated with a significantly worse chemotherapy response and lower overall survival in small cell lung cancer (SCLC).
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    URL: Article
    DOI: 10.1111/tca.v11.9
    DOI: 10.1111/1759-7714.13566
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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  • 10
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    Epigenetic readers and lung cancer: the rs2427964C〉T variant of the bromodomain and extraterminal domain gene BRD3 is associated with poorer survival outcome in NSCLC
    Wiley ; 2022
    In:  Molecular Oncology Vol. 16, No. 3 ( 2022-02), p. 750-763
    Details
    In: Molecular Oncology, Wiley, Vol. 16, No. 3 ( 2022-02), p. 750-763
    Abstract: Bromodomain and extraterminal domain (BET) proteins are epigenetic readers that regulate gene expression. We investigated whether variants in BET genes are associated with survival outcomes for lung cancer. To do this, the associations between 77 variants in BET family genes and survival outcomes were analyzed in 773 non‐small‐cell lung cancer (NSCLC) patients who underwent surgery (349 and 424 patients in the discovery and validation cohorts, respectively). We found that six variants were significantly associated with overall survival (OS) in the discovery cohort, and one variant (rs2506711C 〉 T) was replicated in the validation cohort. BRD3 rs2506711C 〉 T is located in the repressed area and has a strong linkage disequilibrium with rs2427964C 〉 T in the promoter region. BRD3 rs2427964C 〉 T was significantly associated with worse OS in the discovery cohort, validation cohort, and combined analysis. In a luciferase assay, promoter activity in the BRD3 rs2427964 T allele was significantly higher than that in the BRD3 rs2427964 C allele, which selectively bound with the transcriptional repressor SIN3A. Knockdown of BRD3 with BRD3 ‐specific siRNA decreased the proliferation and migration of lung cancer cells while also increasing the rate of apoptosis. These results suggest that BRD3 rs2427964C 〉 T increases BRD3 expression through increased promoter activity, which is associated with poor prognosis for lung cancer.
    Type of Medium: Online Resource
    ISSN: 1574-7891 , 1878-0261
    URL: Issue
    URL: Article
    DOI: 10.1002/mol2.v16.3
    DOI: 10.1002/1878-0261.13109
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2322586-5
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