Validation of previously identified serum biomarkers for breast cancer with SELDI-TOF MS: a case control study

<p>Abstract</p> <p>Background</p> <p>Serum protein profiling seems promising for early detection of breast cancer. However, the approach is also criticized, partly because of difficulties in validating discriminatory proteins. This study's aim is to validate three proteins previously reported to be discriminative between breast cancer cases and healthy controls. These proteins had been identified as a fragment of inter-alpha trypsin inhibitor H4 (4.3 kDa), C-terminal-truncated form of C3a des arginine anaphylatoxin (8.1 kDa) and C3a des arginine anaphylatoxin (8.9 kDa).</p> <p>Methods</p> <p>Serum protein profiles of 48 breast cancer patients and 48 healthy controls were analyzed with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Differences in protein intensity between breast cancer cases and controls were measured with the Mann-Whitney U test and adjusted for confounding in a multivariate logistic regression model.</p> <p>Results</p> <p>Four peaks, with mass-to-charge ratio (<it>m/z</it>) 4276, 4292, 8129 and 8941, were found that were assumed to represent the previously reported proteins. <it>M/</it>z 4276 and 4292 were statistically significantly decreased in breast cancer cases compared to healthy controls (p < 0.001). M/<it>z </it>8941 was decreased in breast cancer cases (p < 0.001) and <it>m/z </it>8129 was not related with breast cancer (p = 0.87). Adjustment for sample preparation day, sample storage duration and age did not substantially alter results.</p> <p>Conclusion</p> <p><it>M/z </it>4276 and 4292 both represented the previously reported 4.3 kDa protein and were both decreased in breast cancer patients, which is in accordance with the results of most previous studies. <it>M/z </it>8129 was in contrast with previous studies not related with breast cancer. Remarkably, <it>m/z </it>8941 was decreased in breast cancer cases whereas in previous studies it was increased. Differences in patient populations and pre-analytical sample handling could have contributed to discrepancies. Further research is needed before we can conclude on the relevance of these proteins as breast cancer biomarkers.</p

Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10−8) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction

Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (PPeer reviewe

Dichroic guest-host polarizer comprising an oriented polymer film

\u3cp\u3eA dichroic guest-host polarizer comprises an oriented polymerized liquid crystal host and aligned therewith a dichroic guest. The dichroic ratio of the polarizer is about 15 or more. The polarizer may have a small thickness, be manufactured using a wet deposition method, optionally in accordance with a desired pattern, and be provided on the inside of a liquid crystal cell. Polymerizable liquid crystals having a highly ordered mesophase which may be suitable used to obtain highly oriented polymer films such as polarizer films are disclosed.\u3c/p\u3

Dichroic guest-host polarizer comprising an oriented polymer film

\u3cp\u3eA dichroic guest-host polarizer comprises an oriented polymerized liquid crystal host and aligned therewith a dichroic guest. The dichroic ratio of the polarizer is about 15 or more. The polarizer may have a small thickness, be manufactured using a wet deposition method, optionally in accordance with a desired pattern, and be provided on the inside of a liquid crystal cell. Polymerizable liquid crystals having a highly ordered mesophase which may be suitable used to obtain highly oriented polymer films such as polarizer films are disclosed.\u3c/p\u3

Birefringent optical element, lcd device with a birefringent optical element, and manufacturing process for a birefringent optical element

\u3cp\u3eA birefringent optical element comprises a polymerized and/or cross-linked mixture (301) of a liquid crystalline compound and a photo-isomerizable compound. The birefringence of the element can be determined with high precision by manipulating the order parameter and polarization anisotropy of said mixture. For this purpose, the photo-isomerizable compound is converted from a trans-form to a cis-form during manufacturing by means of irradiation. Preferably the photo-isomerizable compound is a cinnamate compound. The irradiated mixture is polymerized and/or cross-linked after irradiation. The irradiation preferably takes place through a greyscale mask (305) so that within the mixture (301) portions (302R, 302G, 302B) are defined that obtain different birefringence values. The process is for example suitable for manufacturing a retarder layer or compensation foil inside the liquid crystalline cell of a Liquid Crystal Display (LCD) device, and in particular for manufacturing a patterned retarder layer having portions with different retardation, associated with the primary colors of a color LCD device.\u3c/p\u3