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  • S. Karger AG  (5)
  • Lee, Jang Hyuck  (5)
  • Medizin  (5)
Materialart
Verlag/Herausgeber
  • S. Karger AG  (5)
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  • Medizin  (5)
RVK
  • 1
    In: Oncology, S. Karger AG, Vol. 99, No. 5 ( 2021), p. 336-344
    Kurzfassung: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Activating transcription factor 3 (ATF3) plays a significant role in cancer development and progression. We investigated the association between variants in expression quantitative trait loci (eQTLs) within ATF3 binding regions and the prognosis of non-small cell lung cancer (NSCLC) after surgery. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 A total of 772 patients with NSCLC who underwent curative surgery were enrolled. Using a public database (http://galaxyproject.org), we selected 104 single nucleotide polymorphisms (SNPs) in eQTLs in the ATF3 binding regions. The association of those SNPs with disease-free survival (DFS) was evaluated. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Among those SNPs, 〈 i 〉 HAX1 〈 /i 〉 rs11265425T & #x3e;G was associated with significantly worse DFS (aHR = 1.30, 95% CI = 1.00–1.69, 〈 i 〉 p 〈 /i 〉 = 0.05), and 〈 i 〉 ME3 〈 /i 〉 rs10400291C & #x3e;A was associated with significantly better DFS (aHR = 0.66, 95% CI = 0.46–0.95, 〈 i 〉 p 〈 /i 〉 = 0.03). Regarding 〈 i 〉 HAX1 〈 /i 〉 rs11265425T & #x3e;G, the significant association remained only in adenocarcinoma, and the association was significant only in squamous cell carcinoma regarding 〈 i 〉 ME3 〈 /i 〉 rs10400291C & #x3e;A. ChIP-qPCR assays showed that the two variants reside in active enhancers where H3K27Ac and ATF3 binding occurs. Promoter assays showed that rs11265425 G allele had significantly higher 〈 i 〉 HAX1 〈 /i 〉 promoter activity than T allele. 〈 i 〉 HAX1 〈 /i 〉 RNA expression was significantly higher in tumor than in normal lung, and higher in rs11265425 TG+GG genotypes than in TT genotype. Conversely, 〈 i 〉 ME3 〈 /i 〉 expression was significantly lower in tumor than in normal lung, and higher in rs10400291 AA genotype than in CC+CA genotypes. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 In conclusion, this study shows that the functional polymorphisms in ATF3 binding sites, 〈 i 〉 HAX1 〈 /i 〉 rs11265425T & #x3e;G and 〈 i 〉 ME3 〈 /i 〉 rs10400291C & #x3e;A are associated with the clinical outcomes of patients in surgically resected NSCLC.
    Materialart: Online-Ressource
    ISSN: 0030-2414 , 1423-0232
    RVK:
    Sprache: Englisch
    Verlag: S. Karger AG
    Publikationsdatum: 2021
    ZDB Id: 1483096-6
    ZDB Id: 250101-6
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: Oncology, S. Karger AG, Vol. 98, No. 12 ( 2020), p. 897-904
    Kurzfassung: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 This study was conducted to investigate the association between genetic variants in one-carbon metabolism and survival outcomes of surgically resected non-small cell lung cancer (NSCLC). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We genotyped 41 potentially functional variants of 19 key genes in the one-carbon metabolism pathway among 750 NSCLC patients who underwent curative surgery. The association between genetic variants and overall survival (OS)/disease-free survival (DFS) were analyzed. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Among the 41 single-nucleotide polymorphisms (SNPs) analyzed, 4 SNPs ( 〈 i 〉 MTHFD1L 〈 /i 〉 rs6919680T & #x3e;G and rs3849794T & #x3e;C, 〈 i 〉 MTR 〈 /i 〉 rs2853523C & #x3e;A, and 〈 i 〉 MTHFR 〈 /i 〉 rs4846049G & #x3e;T) were significantly associated with survival outcomes. 〈 i 〉 MTHFD1L 〈 /i 〉 rs6919680T & #x3e;G and 〈 i 〉 MTR 〈 /i 〉 rs2853523C & #x3e;A were significantly associated with better OS (adjusted hazard ratio [aHR] = 0.73, 95% confidence interval [CI] = 0.54–0.99, 〈 i 〉 p 〈 /i 〉 = 0.04) and worse OS (aHR = 2.14, 95% CI = 1.13–4.07, 〈 i 〉 p 〈 /i 〉 = 0.02), respectively. 〈 i 〉 MTHFD1L 〈 /i 〉 rs3849794T & #x3e;C and 〈 i 〉 MTHFR 〈 /i 〉 rs4846049G & #x3e;T were significantly associated with worse DFS (aHR = 1.41, 95% CI = 1.08–1.83, 〈 i 〉 p 〈 /i 〉 = 0.01; and aHR = 1.97, 95% CI = 1.10–3.53, 〈 i 〉 p 〈 /i 〉 = 0.02, respectively). When the patients were divided according to histology, the associations were significant only in squamous cell carcinoma (SCC), but not in adenocarcinoma (AC). In SCC, 〈 i 〉 MTHFD1L 〈 /i 〉 rs6919680T & #x3e;G and 〈 i 〉 MTR 〈 /i 〉 rs2853523C & #x3e;A were significantly associated with better OS (aHR = 0.64, 95% CI = 0.41–1.00, 〈 i 〉 p 〈 /i 〉 = 0.05) and worse OS (aHR = 2.77, 95% CI = 1.11–6.91, 〈 i 〉 p 〈 /i 〉 = 0.03), respectively, and 〈 i 〉 MTHFD1L 〈 /i 〉 rs3849794T & #x3e;C and 〈 i 〉 MTHFR 〈 /i 〉 rs4846049G & #x3e;T were significantly associated with worse DFS (aHR = 1.73, 95% CI = 1.17–2.56, 〈 i 〉 p 〈 /i 〉 = 0.01; and aHR = 2.78, 95% CI = 1.12–6.88, 〈 i 〉 p 〈 /i 〉 = 0.03, respectively). 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Our results suggest that the genetic variants in the one-carbon metabolism pathway could be used as biomarkers for predicting the clinical outcomes of patients with early-stage NSCLC.
    Materialart: Online-Ressource
    ISSN: 0030-2414 , 1423-0232
    RVK:
    Sprache: Englisch
    Verlag: S. Karger AG
    Publikationsdatum: 2020
    ZDB Id: 1483096-6
    ZDB Id: 250101-6
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 3
    In: Oncology, S. Karger AG
    Kurzfassung: Altered lipid metabolism has been reported to be associated with prognosis in multiple cancers. This study aimed to investigate the association of polymorphisms in lipid metabolism pathway genes with survival outcomes in patients with surgically resected non-small cell lung cancer (NSCLC). In total, 744 patients with surgically resected NSCLC (380 in the discovery cohort and 364 in the validation cohort) were included in this study. Among the 176 investigated polymorphisms, ACADSB rs10902859G 〉 A was associated with significantly better overall survival (OS) in the discovery, validation, and combined cohorts. ACADSB rs10902859G 〉 A was located in the repressed region and had strong linkage disequilibrium (D′ = 1.00 and r2 = 0.94), with rs12220683G 〉 C located in the H3K4me3 peak region, which indicates the presence of active promoters. ACADSB rs12220683G 〉 C was also associated with better OS in the discovery, validation, and combined cohorts (in a dominant model; adjusted hazard ratio [aHR] = 0.53, 95% confidence interval [CI] = 0.30–0.94, P = 0.03; aHR = 0.37, 95% CI = 0.15–0.89, P = 0.03; and aHR = 0.47, 95% CI = 0.29–0.75, P = 0.002, respectively). In vitro luciferase assay demonstrated that the promoter activity of ACADSB was significantly increased in the rs12220683 variant C allele compared with that in the wild G allele (P = 3 × 10−5). These results suggest that ACADSB rs12220683G 〉 C increases promoter activity and that increased ACADSB expression may result in better OS in patients with surgically resected NSCLC.
    Materialart: Online-Ressource
    ISSN: 0030-2414 , 1423-0232
    RVK:
    Sprache: Englisch
    Verlag: S. Karger AG
    Publikationsdatum: 2023
    ZDB Id: 1483096-6
    ZDB Id: 250101-6
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 4
    In: Oncology, S. Karger AG, Vol. 101, No. 2 ( 2023), p. 96-104
    Kurzfassung: 〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 This study was conducted to investigate the association between genetic variants in histone modification regions and clinical outcomes of PEM chemotherapy in patients with lung adenocarcinoma. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Potentially functional SNPs were selected using integrated analysis of ChIP-seq and RNA-seq. The associations of 279 SNPs with chemotherapy response and overall survival (OS) were analyzed in 314 lung adenocarcinoma patients who underwent PEM chemotherapy. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Among the SNPs investigated, 18 were significantly associated with response to chemotherapy, while 28 with OS. Of these SNPs, rs549794A & #x3e;G in an enhancer which is expected to regulate the expression of 〈 i 〉 ribosomal protein S3 〈 /i 〉 ( 〈 i 〉 RPS3 〈 /i 〉 ) gene was significantly associated with both worse response to chemotherapy and worse OS (adjusted odds ratio = 0.59, 95% CI = 0.36–0.97, 〈 i 〉 p 〈 /i 〉 = 0.04; adjusted hazard ratio = 1.44, 95% CI = 1.09–1.91, 〈 i 〉 p 〈 /i 〉 = 0.01, respectively). Previous studies suggested that RPS3, a multi-functional protein with various extraribosomal activities, may play a role in chemotherapy resistance. Therefore, it is postulated that rs549794-induced change in the expression level of RPS3 may affect the response to PEM chemotherapy and consequently the survival outcomes in lung adenocarcinoma patients. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 This study suggests that genetic variants in the histone modification regions may be useful for the prediction of clinical outcomes of PEM chemotherapy in advanced lung adenocarcinoma.
    Materialart: Online-Ressource
    ISSN: 0030-2414 , 1423-0232
    RVK:
    Sprache: Englisch
    Verlag: S. Karger AG
    Publikationsdatum: 2023
    ZDB Id: 1483096-6
    ZDB Id: 250101-6
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 5
    In: Oncology, S. Karger AG, Vol. 98, No. 7 ( 2020), p. 468-477
    Kurzfassung: 〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 This study was conducted to investigate whether polymorphisms in glycolysis-related genes are associated with clinical outcomes of patients with advanced-stage non-small cell lung cancer (NSCLC) undergoing chemotherapy. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 A total of 377 patients with NSCLC were enrolled. Sixty-five single-nucleotide polymorphisms in 26 genes involved in the glycolytic pathway were evaluated. The associations of the variants with the chemotherapy response and overall survival (OS) were analyzed. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Among the 65 variants investigated, 〈 i 〉 PFKL 〈 /i 〉 rs2073436C & #x3e;G and 〈 i 〉 GPI 〈 /i 〉 rs7248411C & #x3e;G significantly correlated with clinical outcomes after chemotherapy in multivariate analyses. 〈 i 〉 PFKL 〈 /i 〉 rs2073436C & #x3e;G was significantly associated with both a worse response to chemotherapy (adjusted odds ratio [aOR] = 0.64, 95% CI = 0.45–0.90, 〈 i 〉 p 〈 /i 〉 = 0.01) and a worse OS (adjusted hazard ratio [aHR] = 1.35, 95% CI = 1.14–1.61, 〈 i 〉 p 〈 /i 〉 = 0.001). 〈 i 〉 GPI 〈 /i 〉 rs7248411C & #x3e;G was significantly associated with both a better chemotherapy response (aOR = 1.58, 95% CI = 1.07–2.23, 〈 i 〉 p 〈 /i 〉 = 0.02) and a better OS (aHR = 0.80, 95% CI = 0.66–0.98, 〈 i 〉 p 〈 /i 〉 = 0.03). When stratified by tumor histology, 〈 i 〉 PFKL 〈 /i 〉 rs2073436C & #x3e;G was significantly associated with OS only in squamous cell carcinoma, whereas 〈 i 〉 GPI 〈 /i 〉 rs7248411C & #x3e;G exhibited a significant association with the chemotherapy response and OS only in adenocarcinoma. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 This result suggests that the 〈 i 〉 PFKL 〈 /i 〉 rs2073436C & #x3e;G and 〈 i 〉 GPI 〈 /i 〉 rs7248411C & #x3e;G are useful for predicting the clinical outcome of first-line paclitaxel-cisplatin chemotherapy in NSCLC.
    Materialart: Online-Ressource
    ISSN: 0030-2414 , 1423-0232
    RVK:
    Sprache: Englisch
    Verlag: S. Karger AG
    Publikationsdatum: 2020
    ZDB Id: 1483096-6
    ZDB Id: 250101-6
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
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