Gene expression signatures of angiocidin and darapladib treatment connect to therapy options in cervical cancer

• Published in: Journal of cancer research and clinical oncology Vol. 139; no. 2; pp. 259 - 267
• Main Authors: Koch, Martin, Wiese, Michael
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.02.2013; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Benzaldehydes - therapeutic use; Biological and medical sciences; Biomarkers, Tumor - genetics; Biopsy; Cancer Research; Cancer therapies; Cervical cancer; Cluster Analysis; DNA microarrays; Extracellular matrix; Female; Female genital diseases; Gene expression; Gene Expression Regulation, Neoplastic; Gene set enrichment analysis; Graft-versus-host reaction; Gynecology. Andrology. Obstetrics; Hematology; Human papillomavirus; Humans; Immunological diseases; Internal Medicine; Kidney transplantation; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Staging; Oncology; Original Paper; Oximes - therapeutic use; Pharmacology. Drug treatments; Probes; Proteasome Endopeptidase Complex - therapeutic use; RNA-Binding Proteins; Transcriptome; Tumors; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - pathology; Angiocidin; Darapladib; Cervical cancer; AURKA; Treatment; Malignant tumor; Uterine cervix; Gene expression; Uterine cervix diseases; Cancer; Female genital diseases; Gene expression profile
• ISSN: 0171-5216; 1432-1335; 1432-1335
• DOI: 10.1007/s00432-012-1317-9

Purpose To assign functional properties to gene expression profiles of cervical cancer stages and identify clinically relevant biomarker genes. Experimental design Microarray samples of 24 normal and 102 cervical cancer biopsies from four publicly available studies were pooled and evaluated. High-quality microarrays were normalized using the CONOR package from the Bioconductor project. Gene expression profiling was performed using variance-component analysis for accessing most reliable probes, which were subsequently processed by gene set enrichment analysis. Results Of 22.277 probes that were subject to variance-component analysis, eleven probes had low heterogeneity, that is, a W/T ratio between 0.18 and 0.38. Seven of these probes are induced in all cervical cancer stages: they are GINS1, PAK2, DTL, AURKA, PRKDC, NEK2 and CEP55. The other four probes are induced in normal cervix: P11, EMP1, UPK1A and HSPC159. We performed GSEA of 9.873 probes exhibiting less variability, that is, having a W/T ratio of <0.75. Repeatedly, significant gene expression signatures were found that are related to treatment using angiocidin and darapladib. Additionally, expression signatures from immunological disease signatures were found, for example graft versus host disease and acute kidney rejection. Another finding comprises a gene expression signature in stage IB2 that refers to MT1-MMP-dependent migration and invasion. This gene signature is accompanied by gene expression signatures which refer to ECM receptor-mediated interactions. Conclusion Analysis of cervical cancer patient gene expression data reveals a novel perspective on HPV-mediated transcription processes. This novel point of view contains a better understanding and even might provide improvements to cancer therapy.