| 1. |
- Botling, Johan, et al.
(författare)
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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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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 19:1, s. 194-204
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Tidskriftsartikel (refereegranskat)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. |
- Djureinovic, Dijana, et al.
(författare)
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Profiling cancer testis antigens in non-small-cell lung cancer
- 2016
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Ingår i: JCI INSIGHT. - : American Society for Clinical Investigation. - 2379-3708. ; 1:10
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Tidskriftsartikel (refereegranskat)abstract
- Cancer testis antigens (CTAs) are of clinical interest as biomarkers and present valuable targets for immunotherapy. To comprehensively characterize the CTA landscape of non-small-cell lung cancer (NSCLC), we compared RNAseq data from 199 NSCLC tissues to the normal transcriptome of 142 samples from 32 different normal organs. Of 232 CTAs currently annotated in the Caner Testis Database (CTdatabase), 96 were confirmed in NSCLC. To obtain an unbiased CTA profile of NSCLC, we applied stringent criteria on our RNAseq data set and defined 90 genes as CTAs, of which 55 genes were not annotated in the CTdatabase, thus representing potential new CTAs. Cluster analysis revealed that CTA expression is histology dependent and concurrent expression is common. IHC confirmed tissue-specific protein expression of selected new CTAs (TKTL1, TGIF2LX, VCX, and CXORF67). Furthermore, methylation was identified as a regulatory mechanism of CTA expression based on independent data from The Cancer Genome Atlas. The proposed prognostic impact of CTAs in lung cancer was not confirmed, neither in our RNAseq cohort nor in an independent meta-analysis of 1,117 NSCLC cases. In summary, we defined a set of 90 reliable CTAs, including information on protein expression, methylation, and survival association. The detailed RNAseq catalog can guide biomarker studies and efforts to identify targets for immunotherapeutic strategies.
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| 3. |
- Lohr, Miriam, et al.
(författare)
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The prognostic relevance of tumour-infiltrating plasma cells and immunoglobulin kappa C indicates an important role of the humoral immune response in non-small cell lung cancer
- 2013
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Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835 .- 1872-7980. ; 333:2, s. 222-228
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Tidskriftsartikel (refereegranskat)abstract
- A prognostic impact of immunoglobulin kappa C (IGKC) expression has been described in cancer. We analysed the influence of B-cell and plasma cell markers, as well as IGKC expression, in non-small lung cancer (NSCLC) using immunohistochemistry on a tissue microarray. IGKC protein expression was independently associated with longer survival, with particular impact in the adenocarcinoma subgroup. Moreover, a correlation was seen with CD138+ cells, but not with CD20. CD138 expression revealed a comparable association with survival. In conclusion, IGKC expression in stroma–infiltrating plasma cells is a prognostic marker in NSCLC, supporting emerging treatment concepts that exploit the humoral immune response.
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| 4. |
- Melvin, J. C., et al.
(författare)
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Gamma-glutamyl transferase and c-reactive protein as alternative markers of metabolic abnormalities and their associated comorbidites : A prospective cohort study
- 2012
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Ingår i: International Journal of Molecular Epidemiology and Genetics. - 1948-1756. ; 3:4, s. 276-285
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent studies suggested that gamma-glutamyl transferase (GGT) and C-reactive protein (CRP) are good markers of metabolic abnormalities. We assessed the link between GGT, CRP and common metabolic abnormalities, as well their link to related diseases, such as cancer and cardiovascular disease (CVD). Methods: We selected 333,313 subjects with baseline measurements of triglycerides (TG), total cholesterol (TC), glucose, GGT and CRP in the Swedish AMORIS study. Baseline measurement of BMI was available for 63,900 persons and 77,944 had baseline measurements of HDL. Pearson correlation coefficients between CRP, GGT, and metabolic components (TG, HDL, BMI and TC) were calculated. To investigate the combined effect of GGT and CRP we created a score ranging from 0 to 6 and used Cox proportional hazard models to evaluate its association with CVD and cancer. Results: 21,216 individuals developed cancer and 47,939 CVD. GGT and TG had the strongest correlation (r=0.22). An increased risk of cancer was identified with elevated levels of GGT or CRP or both markers (GGT-CRP score ≥3); the greatest risk of cancer was found when GGT-CRP score = 6 (HR: 1.40 (95%CI: 1.31-1.48) and 1.60 (1.47-1.76) compared to GGT-CRP score = 0, respectively). Conclusion: While GGT and CRP have been shown to be associated with metabolic abnormalities previously, their association to the components investigated in this study was limited. Results did demonstrate that these markers were predictive of associated diseases, such as cancer.
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| 5. |
- Molarius, Anu, et al.
(författare)
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Socioeconomic conditions, lifestyle factors, and self-rated health among men and women in Sweden
- 2007
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Ingår i: European Journal of Public Health. - : Oxford University Press (OUP). - 1101-1262 .- 1464-360X. ; 17:2, s. 125-133
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Tidskriftsartikel (refereegranskat)abstract
- Background: Socioeconomic conditions and lifestyle factors have been found to be related to self-rated health, which is an established predictor of morbidity and mortality. Few studies, however, have investigated the independent effect of material and psychosocial conditions as well as lifestyle factors on self-rated health. Methods: The association between socioeconomic conditions, lifestyle factors, and self-rated health was investigated using a postal survey questionnaire sent to a random population sample of men and women aged 18-79 years during March-May 2000. The overall response rate was 65%. The area investigated covers 58 municipalities in the central part of Sweden. Multivariate odds ratios for poor self-rated health were calculated for a range of variables. A total of 36 048 subjects with full data were included in the analysis. Similar analyses of the influence of working conditions were conducted among those employed aged 18-64 years (17 820 subjects). Results: The overall prevalence of poor self-rated health was 7% among men and 9% among women. Poor self-rated health was most common among persons who had been belittled, who had experienced economic hardship, who lacked social support, or who had retired early. A low educational level was independently associated with poor self-rated health among men, but not among women. Physically inactive as well as underweight and obese subjects were more likely to have poor self-rated health than other subjects. Working conditions associated with poor self-rated health were dissatisfaction with work, low job control and worry about losing one's job. Conclusion: While a cross-sectional study does not allow definite conclusions as to which factors are determinants and which are consequences of poor self-rated, the present findings support the notion that both psychosocial and material conditions as well as lifestyle factors are independently related with poor self-rated health.
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| 7. |
- Schmidt, Marcus, et al.
(författare)
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A comprehensive analysis of human gene expression profiles identifies stromal immunoglobulin kappa C as a compatible prognostic marker in human solid tumors
- 2012
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 18:9, s. 2695-2703
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE:Although the central role of the immune system for tumor prognosis is generally accepted a single robust marker is not yet available.EXPERIMENTAL DESIGN:Based on ROC (receiver operating characteristic) analyses robust markers were identified from a 60 gene B-cell derived metagene and analyzed in gene expression profiles of 1810 breast cancer, 1056 non-small cell lung cancer, 513 colorectal and 426 ovarian cancer patients. Protein and RNA levels were examined in paraffin embedded tissue of 330 breast cancer patients. The cell types were identified using immunohistochemical co-staining and confocal fluorescence microscopy.RESULTS:We identified immunoglobulin kappa C (IGKC) which as a single marker is similarly predictive and prognostic as the entire B-cell metagene. IGKC was consistently associated with metastasis free survival across different molecular subtypes in node-negative breast cancer (n=965) and predicted response to anthracycline-based neoadjuvant chemotherapy (n=845) [P less than 0.001]. In addition, IGKC gene expression was prognostic in non-small cell lung cancer and colorectal cancer. No association was observed in ovarian cancer. IGKC protein expression was significantly associated with survival in paraffin embedded tissues of 330 breast cancer patients. Tumor infiltrating plasma cells were identified as the source of IGKC expressionCONCLUSION:Our findings provide IGKC as a novel diagnostic marker for risk stratification in human cancer and support concepts to exploit the humoral immune response for anti-cancer therapy. It could be validated in several independent cohorts and performed similarly well in RNA from fresh frozen as well as from paraffin tissue and on protein level by immunostaining.
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