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- Peng, Z., et al.
(författare)
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An expression signature at diagnosis to estimate prostate cancer patients' overall survival
- 2014
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Ingår i: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1365-7852 .- 1476-5608. ; 17:1, s. 81-90
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This study aimed to identify biomarkers for estimating the overall and prostate cancer (PCa)-specific survival in PCa patients at diagnosis. METHODS: To explore the importance of embryonic stem cell (ESC) gene signatures, we identified 641 ESC gene predictors (ESCGPs) using published microarray data sets. ESCGPs were selected in a stepwise manner, and were combined with reported genes. Selected genes were analyzed by multiplex quantitative polymerase chain reaction using prostate fine-needle aspiration samples taken at diagnosis from a Swedish cohort of 189 PCa patients diagnosed between 1986 and 2001. Of these patients, there was overall and PCa-specific survival data available for 97.9%, and 77.9% were primarily treated by hormone therapy only. Univariate and multivariate Cox proportional hazard ratios and Kaplan-Meier plots were used for the survival analysis, and a k-nearest neighbor (kNN) algorithm for estimating overall survival. RESULTS: An expression signature of VGLL3, IGFBP3 and F3 was shown sufficient to categorize the patients into high-, intermediate- and low-risk subtypes. The median overall survival times of the subtypes were 3.23, 4.00 and 9.85 years, respectively. The difference corresponded to hazard ratios of 5.86 (95% confidence interval (CI): 2.91-11.78, P<0.001) for the high-risk subtype and 3.45 (95% CI: 1.79-6.66, P<0.001) for the intermediate-risk compared with the low-risk subtype. The kNN models that included the gene expression signature outperformed the one designed on clinical parameters alone. CONCLUSIONS: The expression signature can potentially be used to estimate overall survival time. When validated in future studies, it could be integrated in the routine clinical diagnostic and prognostic procedure of PCa for an optimal treatment decision based on the estimated survival benefit.
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| 2. |
- Bergqvist, Jenny, et al.
(författare)
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Quantitative real-time PCR analysis and microarray-based RNA expression of HER2 in relation to outcome
- 2007
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 18:5, s. 845-850
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Our aim was to use quantitative real-time PCR (Q-PCR) and RNA expression profiles (RNA-EPs) to investigate HER2 status in relation to outcome. PATIENTS AND METHODS: Cut-off levels for Q-PCR and RNA-EP were established in relation to immunohistochemistry (IHC) validated by FISH in a test set of frozen tissue samples from 40 primary breast cancers. The HER2 status was subsequently studied in another validation set of 306 tumors, where Q-PCR and RNA-EP results were compared with previously carried out IHC that we had validated by chromogenic in situ hybridization (CISH). RESULTS: Q-PCR and RNA-EP offered similar sensitivity (90% versus 77%), specificity (93% versus 95%), and negative (99% versus 98%) and positive (63% versus 61%) predictive values for HER2 determinations. Analyses of relapse-free survival (RFS) and overall survival on the basis of 5 and 10 years of follow-up indicated equivalent hazard ratios for all three techniques. In contrast to IHC/CISH, both Q-PCR and RNA-EP analyses of HER2 also gave statistically significant results regarding RFS and breast cancer-corrected survival after 10 years of follow-up. CONCLUSION: The use of RNA-EP and Q-PCR to analyze HER2 in frozen and formalin-fixed breast cancer samples may be an alternate approach to IHC in combination with FISH/CISH.
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| 4. |
- Li, CD, et al.
(författare)
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A gene expression signature to predicit overall, prostate cancer, and non-prostate cancer survival
- 2013
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Ingår i: JOURNAL OF CLINICAL ONCOLOGY. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 31:6
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- 51 Background: For prostate cancer patients, prostate cancer specific and non-prostate cancer specific survival have the same importance. This study aimed at identifying expression biomarkers that can predict prostate cancer specific, non-prostate cancer specific and overall survival at diagnosis. Methods: Selected ESCGPs (embryonic stem cell gene predictors) and control genes were analyzed by multiplex quantitative PCR using prostate fine-needle aspiration samples taken at diagnosis from a Swedish cohort of 189 prostate cancer patients diagnosed between 1986 and 2000. Of all patients, 97.9% had overall and cancer-specific survival data and 77.9% were primarily treated only by hormone therapy. The cohort was divided into one discovery and two validation subsets. Univariate and multivariate Cox proportional hazard ratios and Kaplan-Meier plots were used for the survival analysis. A published dataset was used for external validation. Results: An expression signature of F3, VGLL3 and IGFBP3, was sufficient to categorize the patients into high-risk, intermediate-risk and low-risk subtypes. The median overall survival of the subtypes was 3.23, 4.00 and 9.85 years respectively. The difference corresponded to HRs of 5.86 (95% CI 2.91-11.78, P<0.001) for the high-risk and 3.45 (95% CI 1.79-6.66, P<0.001) for the intermediate-risk compared to the low-risk subtype. This signature is significant in correlation to overall, cancer-specific and non-cancer specific survival in both univariate and multivariate analyses including common clinical parameters. Conclusions: These results suggest that these novel expression biomarkers and the expression signature could be used to improve the accuracy of the currently available clinical tools for predicting overall, cancer-specific and non-cancer specific survival and selecting patients with potential survival benefit from hormone treatment.
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| 10. |
- Gunnarsson, Mikael, et al.
(författare)
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No radiation protection reasons for restrictions on C-14 urea breath tests in children.
- 2002
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Ingår i: British Journal of Radiology. - : British Institute of Radiology. - 1748-880X .- 0007-1285. ; 75:900, s. 982-986
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Tidskriftsartikel (refereegranskat)abstract
- Traditional 14C urea breath tests are normally not used for younger children because the radiation exposure is unknown. High sensitivity accelerator mass spectrometry and an ultra-low amount (440 Bq) of 14C urea were therefore used both to diagnose Helicobacter pylori (HP) infection in seven children, aged 3–6 years, and to make radiation dose estimates. The activity used was 125 times lower than the amount normally used for older children and 250 times lower than that used for adults. Results were compared with previously reported biokinetic and dosimetric data for adults and older children aged 7–14 years. 14C activity concentrations in urine and exhaled air per unit administered activity for younger children (3–6 years) correspond well with those for older children (7–14 years). For a child aged 3–6 years who is HP negative, the urinary bladder wall receives the highest absorbed dose, 0.3 mGy MBq-1. The effective dose is 0.1 mSv MBq-1 for the 3-year-old child and 0.07 mSv MBq-1 for the 6-year-old child. For two children, the 10 min and 20 min post-14C administration samples of exhaled air showed a significantly higher amount of 14C activity than for the rest of the children, that is 6% and 19% of administered activity exhaled per hour compared with 0.3–0.9% (mean 0.5%) of administered activity exhaled per hour indicating that these two children that is were HP positive. For a 3-year-old HP positive child, absorbed dose to the urinary bladder wall was 0.3 mGy MBq-1 and effective dose per unit of administered activity was 0.4 mSv MBq-1. Using 55 kBq, which is a normal amount for older children when liquid scintillation counters are used for measurement, the effective dose will be approximately 6 µSv to a 3-year-old HP negative child and 20 µSv to a HP positive child. Thus there is no reason for restrictions on performing a normal 14C urea breath test, even on young children.
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