Additional file 1: of Cross-talk between the Tissue Factor/coagulation factor VIIa complex and the tyrosine kinase receptor EphA2 in cancer

Supplemental Figures. (PDF 2.19 MB

Analysis of Candidate Genes for Lineage-Specific Expression Changes in Humans and Primates

RUNX2, a gene involved in skeletal development, has previously been shown to be potentially affected by positive selection during recent human evolution. Here we have used antibody-based proteomics to characterize potential differences in expression patterns of RUNX2 interacting partners during primate evolution. Tissue microarrays consisting of a large set of normal tissues from human and macaque were used for protein profiling of 50 RUNX2 partners with immunohistochemistry. Eleven proteins (AR, CREBBP, EP300, FGF2, HDAC3, JUN, PRKD3, RUNX1, SATB2, TCF3, and YAP1) showed differences in expression between humans and macaques. These proteins were further profiled in tissues from chimpanzee, gorilla, and orangutan, and the corresponding genes were analyzed with regard to genomic features. Moreover, protein expression data were compared with previously obtained RNA sequencing data from six different organs. One gene (TCF3) showed significant expression differences between human and macaque at both the protein and RNA level, with higher expression in a subset of germ cells in human testis compared with macaque. In conclusion, normal tissues from macaque and human showed differences in expression of some RUNX2 partners that could be mapped to various defined cell types. The applied strategy appears advantageous to characterize the consequences of altered genes selected during evolution

Analysis of Candidate Genes for Lineage-Specific Expression Changes in Humans and Primates

<i>RUNX2</i>, a gene involved in skeletal development, has previously been shown to be potentially affected by positive selection during recent human evolution. Here we have used antibody-based proteomics to characterize potential differences in expression patterns of RUNX2 interacting partners during primate evolution. Tissue microarrays consisting of a large set of normal tissues from human and macaque were used for protein profiling of 50 RUNX2 partners with immunohistochemistry. Eleven proteins (AR, CREBBP, EP300, FGF2, HDAC3, JUN, PRKD3, RUNX1, SATB2, TCF3, and YAP1) showed differences in expression between humans and macaques. These proteins were further profiled in tissues from chimpanzee, gorilla, and orangutan, and the corresponding genes were analyzed with regard to genomic features. Moreover, protein expression data were compared with previously obtained RNA sequencing data from six different organs. One gene (<i>TCF3</i>) showed significant expression differences between human and macaque at both the protein and RNA level, with higher expression in a subset of germ cells in human testis compared with macaque. In conclusion, normal tissues from macaque and human showed differences in expression of some RUNX2 partners that could be mapped to various defined cell types. The applied strategy appears advantageous to characterize the consequences of altered genes selected during evolution

Analysis of Candidate Genes for Lineage-Specific Expression Changes in Humans and Primates

<i>RUNX2</i>, a gene involved in skeletal development, has previously been shown to be potentially affected by positive selection during recent human evolution. Here we have used antibody-based proteomics to characterize potential differences in expression patterns of RUNX2 interacting partners during primate evolution. Tissue microarrays consisting of a large set of normal tissues from human and macaque were used for protein profiling of 50 RUNX2 partners with immunohistochemistry. Eleven proteins (AR, CREBBP, EP300, FGF2, HDAC3, JUN, PRKD3, RUNX1, SATB2, TCF3, and YAP1) showed differences in expression between humans and macaques. These proteins were further profiled in tissues from chimpanzee, gorilla, and orangutan, and the corresponding genes were analyzed with regard to genomic features. Moreover, protein expression data were compared with previously obtained RNA sequencing data from six different organs. One gene (<i>TCF3</i>) showed significant expression differences between human and macaque at both the protein and RNA level, with higher expression in a subset of germ cells in human testis compared with macaque. In conclusion, normal tissues from macaque and human showed differences in expression of some RUNX2 partners that could be mapped to various defined cell types. The applied strategy appears advantageous to characterize the consequences of altered genes selected during evolution

FGF2 as a potential prognostic biomarker for proneural glioma patients

<div><p></p><p><b>Background.</b> The survival of high-grade glioma patients is poor and the treatment of these patients can cause severe side effects. This fosters the necessity to identify prognostic biomarkers, in order to optimize treatment and diminish unnecessary suffering of patients. The aim of this study was to identify prognostic biomarkers for high-grade glioma patients.</p><p><b>Methods.</b> Eleven proteins were selected for analysis due to their suggested importance for survival of patients with other types of cancers and due to a high variation in protein levels between glioma patients (according to the Human Protein Atlas, <a href="http://www.proteinatlas.org" target="_blank">www.proteinatlas.org</a>). Protein expression patterns of these 11 proteins were analyzed by immunohistochemistry in tumor samples from 97 high-grade glioma patients. The prognostic values of the proteins were analyzed with univariate and multivariate Cox regression analyses for the high-grade glioma patients, including subgroup analyses of histological subtypes and immunohistochemically defined molecular subtypes.</p><p><b>Results.</b> The proteins with the most significant (univariate and multivariate p < 0.05) correlations were analyzed further with cross-validated Kaplan-Meier analyses for the possibility of predicting survival based on the protein expression pattern of the corresponding candidate. Random Forest classification with variable subset selection was used to analyze if a protein signature consisting of any combination of the 11 proteins could predict survival for the high-grade glioma patients and the subgroup with glioblastoma patients. The proteins which correlated most significantly (univariate and multivariate p < 0.05) to survival in the Cox regression analyses were Myc for all high-grade gliomas and FGF2, CA9 and CD44 for the subgroup of proneural gliomas, with FGF2 having a strong negative predictive value for survival. No prognostic signature of the proteins could be found.</p><p><b>Conclusion.</b> FGF2 is a potential prognostic biomarker for proneural glioma patients, and warrants further investigation.</p></div

Additional file 6: Table S5. of A systematic search strategy identifies cubilin as independent prognostic marker for renal cell carcinoma

CUBN positivity rates according to tumor site. (DOC 30 kb

Additional file 3: Table S3. of A systematic search strategy identifies cubilin as independent prognostic marker for renal cell carcinoma

Available clinicopathological parameters of primary tumors in cohort 2 and cohort 3. (DOC 31 kb

Additional file 5: Figure S1. of A systematic search strategy identifies cubilin as independent prognostic marker for renal cell carcinoma

Comparison of CUBN mRNA and IHC-derived protein expression in normal tissue. mRNA and protein expression levels were indicated as a percentage of the maximum. IHC-derived expression values were assigned numerical values; three for strong, two for moderate and one for weak staining. Staining intensities were averaged over the number of available tissue microarray cores (three cores per tissue type). (TIF 1128 kb

Additional file 5: Figure S1. of A systematic search strategy identifies cubilin as independent prognostic marker for renal cell carcinoma

Comparison of CUBN mRNA and IHC-derived protein expression in normal tissue. mRNA and protein expression levels were indicated as a percentage of the maximum. IHC-derived expression values were assigned numerical values; three for strong, two for moderate and one for weak staining. Staining intensities were averaged over the number of available tissue microarray cores (three cores per tissue type). (TIF 1128 kb

Additional file 1: Table S1. of A systematic search strategy identifies cubilin as independent prognostic marker for renal cell carcinoma

Test TMA cohort composition. (DOC 34 kb