| 1. |
- Botling, Johan, et al.
(author)
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Biomarker Discovery in Non-Small Cell Lung Cancer : Integrating Gene Expression Profiling, Meta-analysis, and Tissue Microarray Validation
- 2013
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In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 19:1, s. 194-204
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Journal article (peer-reviewed)abstract
- Purpose: Global gene expression profiling has been widely used in lung cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis and therapy response. So far, the value of these multigene signatures in clinical practice is unclear, and the biologic importance of individual genes is difficult to assess, as the published signatures virtually do not overlap.Experimental Design: Here, we describe a novel single institute cohort, including 196 non-small lung cancers (NSCLC) with clinical information and long-term follow-up. Gene expression array data were used as a training set to screen for single genes with prognostic impact. The top 450 probe sets identified using a univariate Cox regression model (significance level P < 0.01) were tested in a meta-analysis including five publicly available independent lung cancer cohorts (n = 860).Results: The meta-analysis revealed 14 genes that were significantly associated with survival (P < 0.001) with a false discovery rate < 1%. The prognostic impact of one of these genes, the cell adhesion molecule 1 (CADM1), was confirmed by use of immunohistochemistry on tissue microarrays from 2 independent NSCLC cohorts, altogether including 617 NSCLC samples. Low CADM1 protein expression was significantly associated with shorter survival, with particular influence in the adenocarcinoma patient subgroup.Conclusions: Using a novel NSCLC cohort together with a meta-analysis validation approach, we have identified a set of single genes with independent prognostic impact. One of these genes, CADM1, was further established as an immunohistochemical marker with a potential application in clinical diagnostics. Clin Cancer Res; 19(1); 194-204. (c) 2012 AACR.
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| 2. |
- Fernandes, Oswaldo J. C. B., et al.
(author)
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Prognostic factors for the survival of surgically treated patients for non-small cell lung cancer
- 2003
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In: Acta Oncologica. - Oslo, Norway : Taylor & Francis. - 0284-186X .- 1651-226X. ; 42:4, s. 338-341
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Journal article (peer-reviewed)abstract
- The survival and outcome rates of 284 patients who underwent surgical treatment for non-small cell lung cancer were assessed retrospectively. Resectability rate was 94.1%, hospital mortality 3.9% (n = 11) and the mortality rates in patients who underwent pneumonectomy or lobectomy were 8.9% and 0.6%, respectively. The overall 5-year survival was 43.6%. Female gender, earlier stages of disease and a complete resection were strongly predictive for a long-term survival. Women in stage IA disease had a 5-year survival rate of 92.7%. The 5-year survival rate for patients in stages IIIA and N2 disease who underwent a complete resection was 21.9%, and 9% for those who did not undergo a complete resection. It is concluded that the best surgical results were observed in women who were operated on at an early stage of disease. A complete resection also contributed to a better outcome, even for patients in stage IIIA and N2 disease.
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| 3. |
- Karlsson, Christina, et al.
(author)
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Estrogen receptor β in NSCLC : prevalence, proliferative influence, prognostic impact and smoking
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Other publication (other academic/artistic)abstract
- In non-small cell lung carcinoma (NSCLC) there are gender differences. The female gender is associated with more adenocarcinomas (ADCA), among both smokers and non-smokers compared to men. Women with NSCLC have a better prognosis compared to men, regardless of other factors. A possible role for estrogen receptor (ER) signalling has been proposed and experimental as well as epidemiological data supports this view. In a material of NSCLC (n=262), ERβ and cyclins A and A2 were studied by immunohistochemistry on formalin-fixed paraffin embedded tissue. In 137 of those cases, frozen material was available, on which expression analysis of ESR2 (ERβ) and cyclin A1 were performed. Data was correlated to histology, gender, smoking habits, stage and clinical outcome.ERβ was expressed in 86% of the cases. ERβ was most frequently expressed in Stage I ADCAs, especially in male subjects. A correlation between ERβ expression and cyclins was observed in ADCA, also with a male predominance. ERβ transcripts had a positive prognostic impact in ADCA. ERβ transcripts were also increased in NSCLC among smokers compared to non-smokers.In conclusion, we report data supporting a role for ERβ in lung ADCAs where ERβ could be a biomarker for future targeted therapies.
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| 4. |
- Karlsson, Christina, 1968-, et al.
(author)
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Oestrogen receptor ss in NSCLC : prevalence, proliferative influence, prognostic impact and smoking
- 2012
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In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - Malden, USA : Wiley-Blackwell. - 0903-4641 .- 1600-0463. ; 120:6, s. 451-458
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Journal article (peer-reviewed)abstract
- In non-small-cell lung carcinoma (NSCLC) there are gender differences. The female gender is associated with more adenocarcinomas (ADCA), among both smokers and non-smokers compared to men. Women with NSCLC have a better prognosis compared to men, regardless of other factors. A possible role for oestrogen receptor (ER) signalling has been proposed. The role for ER beta in NSCLC is still not clear, especially concerning the impact of smoking. In a material of NSCLC (n = 262), ER beta and cyclins A1 and A2 were studied by immunohistochemistry on formalin-fixed paraffin embedded tissue. In 137 of those cases, frozen material was available, on which expression analysis of ESR2 (ER beta) and cyclin A1 were performed. Data were correlated to histology, gender, smoking habits, stage and clinical outcome. ER beta was expressed in 86% of the cases. ER beta was most frequently expressed in Stage I ADCAs, especially in male subjects. A correlation between ER beta expression and cyclins was observed in ADCA, also with a male predominance. ER beta transcripts had a positive prognostic impact in ADCA. ER beta transcripts were increased in NSCLC among smokers compared to non-smokers. In conclusion, our data support a role for ER beta in lung ADCAs, proposing a role for ER beta in lungcarcinogenesis, especially among smokers.
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