title: Genes associated with the tumour microenvironment are differentially expressed in cured versus primary chemotherapy-refractory diffuse large B-cell lymphoma.
abstract: In order to identify genes associated with primary chemotherapy-resistance, gene expression profiles (GEP) in tumour tissue from 37 patients with de novo diffuse large B-cell lymphoma (DLBCL), stage II-IV, either in continuous complete remission (n = 24) or with progressive disease during primary treatment (n = 13), were examined using spotted 55K oligonucleotide arrays. Immunohistochemistry was used for confirmation at the protein level. The top 86 genes that best discriminated between the two cohorts were chosen for further analysis. Only seven of 86 genes were overexpressed in the refractory cohort, e.g. RABGGTB and POLE, both potential targets for drug intervention. Seventy-nine of 86 genes were overexpressed in the cured cohort and mainly coded for proteins expressed in the tumour microenvironment, many of them involved in proteolytic activity and remodelling of extra cellular matrix. Furthermore, major histocompatibility complex class I molecules, CD3D and ICAM1 were overexpressed, indicating an enhanced immunological reaction. Immunohistochemistry confirmed the GEP results. The frequency of tumour infiltrating lymphocytes, macrophages, and reactive cells expressing ICAM-1, lysozyme, cathepsin D, urokinase plasminogen activator receptor, signal transducer and activator of transcription 1, and galectin-3 was higher in the cured cohort. These findings indicate that a reactive microenvironment has an impact on the outcome of chemotherapy in DLBCL.
authors.affiliation: Department of Oncology, Lund University Hospital, Lund, Sweden. johan.linderoth@med.lu.se
authors.forename: Johan
authors.initials: J
authors.lastname: Linderoth
authors.forename: Patrik
authors.initials: P
authors.lastname: Edén
authors.forename: Mats
authors.initials: M
authors.lastname: Ehinger
authors.forename: Jeanette
authors.initials: J
authors.lastname: Valcich
authors.forename: Mats
authors.initials: M
authors.lastname: Jerkeman
authors.forename: Pär-Ola
authors.initials: PO
authors.lastname: Bendahl
authors.forename: Mattias
authors.initials: M
authors.lastname: Berglund
authors.forename: Gunilla
authors.initials: G
authors.lastname: Enblad
authors.forename: Martin
authors.initials: M
authors.lastname: Erlanson
authors.forename: Göran
authors.initials: G
authors.lastname: Roos
authors.forename: Eva
authors.initials: E
authors.lastname: Cavallin-Ståhl
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005500:Follow-Up Studies; D020869:Gene Expression Profiling / Q000379:methods*; D052138:Genes, Neoplasm; D006801:Humans; D007124:Immunoenzyme Techniques; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm