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- Sandberg, AnnSofi, et al.
(författare)
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Tumor Proteomics by Multivariate Analysis on Individual Pathway Data for Characterization of Vulvar Cancer Phenotypes
- 2012
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Vulvar squamous cell carcinoma (VSCC) is the fourth most common gynecological cancer. Based on etiology VSCC is divided into two subtypes; one related to high-risk human papilloma virus (HPV) and one HPV negative. The two subtypes are proposed to develop via separate intracellular signaling pathways. We investigated a suggested link between HPV infection and relapse risk in VSCC through in-depth protein profiling of 14 VSCC tumor specimens. The tumor proteomes were analyzed by liquid-chromatography tandem mass spectrometry. Relative protein quantification was performed by 8-plex isobaric tags for relative and absolute quantification. Labeled peptides were fractionated by high-resolution isoelectric focusing prior to liquid-chromatography tandem mass spectrometry to reduce sample complexity. In total, 1579 proteins were regarded as accurately quantified and analyzed further. For classification of clinical groups, data analysis was performed by comparing protein level differences between tumors defined by HPV and/or relapse status. Further, we performed a biological analysis on individual tumor proteomes by matching data to known biological pathways. We here present a novel analysis approach that combines pathway alteration data on individual tumor level with multivariate statistics for HPV and relapse status comparisons. Four proteins (signal transducer and activator of transcription-1, myxovirus resistance protein 1, proteasome subunit alpha type-5 and legumain) identified as main classifiers of relapse status were validated by immunohistochemistry (IHC). Two of the proteins are interferon-regulated and on mRNA level known to be repressed by HPV. By both liquid-chromatography tandem mass spectrometry and immunohistochemistry data we could single out a subgroup of HPV negative/relapse-associated tumors. The pathway level data analysis confirmed three of the proteins, and further identified the ubiquitin-proteasome pathway as altered in the high risk subgroup. We show that pathway fingerprinting with resolution on individual tumor level adds biological information that strengthens a generalized protein analysis. Molecular & Cellular Proteomics 11: 10.1074/mcp.M112.016998, 1-14, 2012.
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| 2. |
- Sjöström, Susanne, et al.
(författare)
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Medical Abortion Provided by Nurse-Midwives or Physicians in a High Resource Setting : A Cost-Effectiveness Analysis
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective The objective of the present study is to calculate the cost-effectiveness of early medical abortion performed by nurse-midwifes in comparison to physicians in a high resource setting where ultrasound dating is part of the protocol. Non-physician health care professionals have previously been shown to provide medical abortion as effectively and safely as physicians, but the cost-effectiveness of such task shifting remains to be established. Study design A cost effectiveness analysis was conducted based on data from a previously published randomized-controlled equivalence study including 1180 healthy women randomized to the standard procedure, early medical abortion provided by physicians, or the intervention, provision by nurse-midwifes. A 1.6% risk difference for efficacy defined as complete abortion without surgical interventions in favor of midwife provision was established which means that for every 100 procedures, the intervention treatment resulted in 1.6 fewer incomplete abortions needing surgical intervention than the standard treatment. The average direct and indirect costs and the incremental cost-effectiveness ratio (ICER) were calculated. The study was conducted at a university hospital in Stockholm, Sweden. Results The average direct costs per procedure were EUR 45 for the intervention compared to EUR 58.3 for the standard procedure. Both the cost and the efficacy of the intervention were superior to the standard treatment resulting in a negative ICER at EUR -831 based on direct costs and EUR -1769 considering total costs per surgical intervention avoided. Conclusion Early medical abortion provided by nurse-midwives is more cost-effective than provision by physicians. This evidence provides clinicians and decision makers with an important tool that may influence policy and clinical practice and eventually increase numbers of abortion providers and reduce one barrier to women's access to safe abortion.
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