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Transcription profiling of human immune dysregulation/tumor-associated gene changes in recurrent respiratory papillomatosis

ABSTRACT: The goal of this study was to determine the differential expression of specific genes within the papilloma tissues themselves and to characterize the array of host genes that might be important in the pathophysiology of recurrent respiratory papillomatosis. Experiment Overall Design: Total RNAs from papillomas (n=12) and adjacent tissues (n=12) were analyzed by Affymetrix microarray, and the matched sets of tissues compared by Genesifter paired t-test to identify differentially expressed genes in papilloma tissues while minimizing variations that are intrinsic to individual patients.

ORGANISM(S): Homo sapiens

SUBMITTER: James Allen DeVoti

PROVIDER: E-GEOD-10935 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Immune dysregulation and tumor-associated gene changes in recurrent respiratory papillomatosis: a paired microarray analysis.

DeVoti James A JA Rosenthal David W DW Wu Rong R Abramson Allan L AL Steinberg Bettie M BM Bonagura Vincent R VR

Molecular medicine (Cambridge, Mass.) 20080901 9-10

Recurrent respiratory papillomas (RRP) are benign airway tumors, caused primarily by human papillomaviruses (HPV) types 6 and 11. The disease is characterized by multiple recurrences after surgical removal, with limited effective therapy. To identify novel targets for future therapy, we established transcriptional profiles for actively growing papillomas compared with autologous, clinically normal, laryngeal epithelia (adjacent tissue). Total ribonucleic acid (RNA) from 12 papillomas and 12 adja ...[more]

PMID: 18607510

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Immune Dysregulation/Tumor-Associated Gene Changes in Recurrent Respiratory Papillomatosis: A Paired Microarray Analysis

Project description:The goal of this study was to determine the differential expression of specific genes within the papilloma tissues themselves and to characterize the array of host genes that might be important in the pathophysiology of recurrent respiratory papillomatosis. Keywords: papilloma vs normal adjacent autologous larynx

2008-07-16 | GSE10935 | GEO

Network Analysis of Skin Tumor Progression Identifies a Rewired Genetic Architecture Affecting Inflammation and Tumor Susceptibility (papillomas)

Project description:Germline polymorphisms influence gene expression networks in normal mammalian tissues. Analysis of this genetic architecture can identify single genes and whole pathways that influence to complex traits including inflammation and cancer susceptibility. Changes in the genetic architecture during the development of benign and malignant tumours have not been investigated. Here, we document major changes in germline control of gene expression during skin tumour development as a consequence of cell selection, somatic genetic events, and changes in tumour microenvironment. Immune response genes such as Interleukin 18 and Granzyme E are under germline control in tumours but not in normal skin. Gene expression networks linked to tumour susceptibility and hair follicle stem cell markers in normal skin undergo significant reorganization during tumour progression. Our data highlight opposing roles of Interleukin-1 signaling networks in tumour susceptibility and tumour progression and have implications for the development of chemopreventive strategies to reduce cancer incidence. Skin tumors were induced on dorsal back skin from a Mus spretus / Mus musculus backcross ([SPRET/Ei X FVB/N] X FVB/N) mice by treatment of dorsal back skin with dimethyl benzanthracene (DMBA) and tetradecanoyl-phorbol acetate (TPA). This treatment induced multiple benign papillomas as well as malignant squamous cell carcinomas (SCC) and spindle cell carcinomas. Gene expression analysis was performed on mRNA extracted from 68 papillomas: two papillomas from each of 31 FVBBX mice and a single papilloma from six additional FVBBX mice. Papillomas were harvested when mice were sacrificed due to presence of a carcinoma or termination of the experiment.

2010-12-22 | E-GEOD-21263 | biostudies-arrayexpress

Identification of Genes and Gene Ontology Process Critical to Skin Papilloma Development in Tg.AC Transgenic Mice

Project description:This study analyzes gene expression associated with papilloma development in Tg.AC v-Ha-ras transgenic mice and identifies novel genes and biological processes that may be critical to skin carcinogenesis in these mice. Epidermal abrasion was used to synchronously induce epidermal regeneration in FVB/N wild type and transgenic Tg.AC mice. Skin papillomagenesis was uniquely induced in Tg.AC mice, and gene expression profiling was carried out using a 22,000 element mouse DNA microarray. Histological analysis showed that papillomas developed at a high rate by day 30 after abrasion in transgenic animals, while no papilloma developed in wild type mice. Transgene specific differentially expressed genes were identified at day 30 post-abrasion and these genes were annotated using EASE software and literature mining. Annotated and non-annotated genes associated with papilloma development were identified and clustering analysis revealed groups of genes that are coordinately expressed. A number of genes associated with differentiation and development were also physically clustered on mouse chromosome 16, including 16B3 that contains several Stefins and stefin-like genes, and 16A1 containing a number of keratin associated protein genes. Additional analyses presented here yield novel insights into the genes and processes involved in papilloma development in Tg.AC mice. Keywords: Time course of papilloma tumorigenesis between genetically modified strains after skin abrasion.

2008-04-11 | GSE11136 | GEO

Genomic copy-number aberrations in ductal carcinomas in situ with and without invasive components

Project description:In the breast, the reduction of invasive ductal carcinoma (IDC) seems to be smaller than expected from an increasing number of ductal carcinoma in situ (DCIS) detection in screening programs, suggesting that some DCIS lesions remain dormant and take a very long time for progression to IDC. However, the progression risk of individual DCIS and papilloma to IDC largely remain unassessable. To tackle this problem, we applied array-based comparative genomic hybridization to DCIS, IDC and papilloma lesions. We confirmed the presence of chromosomal copy-number alterations (CNAs) reported previously in breast cancers and the absence of chromosomal CNAs in the papillomas examined. These findings suggest that gene CNA profile is a good lineage marker for prediction of progression risk of individual tumors and that tumor progression within each lineage is driven by epigenetic rather than genetic alterations.

2016-09-16 | GSE86988 | GEO

Transcription profiling of mouse FVB/N wild type and transgenic Tg.AC mice to examine skin papilloma development

Project description:This study analyzes gene expression associated with papilloma development in Tg.AC v-Ha-ras transgenic mice and identifies novel genes and biological processes that may be critical to skin carcinogenesis in these mice. Epidermal abrasion was used to synchronously induce epidermal regeneration in FVB/N wild type and transgenic Tg.AC mice. Skin papillomagenesis was uniquely induced in Tg.AC mice, and gene expression profiling was carried out using a 22,000 element mouse DNA microarray. Histological analysis showed that papillomas developed at a high rate by day 30 after abrasion in transgenic animals, while no papilloma developed in wild type mice. Transgene specific differentially expressed genes were identified at day 30 post-abrasion and these genes were annotated using EASE software and literature mining. Annotated and non-annotated genes associated with papilloma development were identified and clustering analysis revealed groups of genes that are coordinately expressed. A number of genes associated with differentiation and development were also physically clustered on mouse chromosome 16, including 16B3 that contains several Stefins and stefin-like genes, and 16A1 containing a number of keratin associated protein genes. Additional analyses presented here yield novel insights into the genes and processes involved in papilloma development in Tg.AC mice. Experiment Overall Design: Strains: Tg.AC vs FVB/N; Treatment: epidermal abrasion vs sham treatment, samples collected 3, 5, 9, 18, and 30 days post treatment; Microarray: 2-channel, pooled total RNA from 5 animals, 2 technical replicate arrays with dye-swaps.

2008-06-11 | E-GEOD-11136 | biostudies-arrayexpress

Immune dysregulation and tumor-associated gene changes in recurrent respiratory papillomatosis: a paired microarray analysis.

Project description:Recurrent respiratory papillomas (RRP) are benign airway tumors, caused primarily by human papillomaviruses (HPV) types 6 and 11. The disease is characterized by multiple recurrences after surgical removal, with limited effective therapy. To identify novel targets for future therapy, we established transcriptional profiles for actively growing papillomas compared with autologous, clinically normal, laryngeal epithelia (adjacent tissue). Total ribonucleic acid (RNA) from 12 papillomas and 12 adjacent tissues were analyzed by microarray, and the matched sets of tissues compared by paired t test, to identify differentially expressed genes in papilloma tissues while minimizing variations intrinsic to individual patients. Quantitative polymerase chain reaction (PCR) was used to confirm the relative expression levels for a subset of genes. Within the 109 differentially expressed transcripts whose expression varied at least three-fold were two large groups of genes with related functions. The first group consisted of 18 genes related to host defense, including both innate and adaptive immunity. The second group contained 37 genes that likely contribute to growth of papillomas as benign tumors, since the altered pattern of expression also had been reported previously in many cancers. Our results support our previous studies that document a systemic T(H)2-like adaptive immune response in RRP, and suggest that there is a role for altered innate immunity in RRP as well. We propose that HPV 6 and 11 infection establishes a tumorigenic microenvironment characterized by alteration of both innate inflammatory signals and adaptive immune responses that prevent effective T(H)1-like response, in conjunction with altered expression of numerous genes that regulate cellular growth and differentiation.

| S-EPMC2442987 | biostudies-literature

Recurrent respiratory papillomatosis with lung involvement.

Project description:Recurrent respiratory papillomatosis (RRP) is a rare disease caused by human papillomavirus. Aggressive forms of RRP require repeated cytoreductive surgery to restore airway patency. Tracheal disease is even less common and lung parenchyma is involved in less than 1% of patients. We present reports of three cases of RRP with progressive lung disease in adult patients.

| S-EPMC6214881 | biostudies-other

Recurrent respiratory papillomatosis: A 2020 perspective.

Project description:ObjectiveDespite recent advancement recurrent respiratory papillomatosis (RRP) remains a rare but challenging benign airway neoplasm. In recent years there has been significant shifts in incidence of this disease due to changes in vaccination and prevention for human papilloma virus (HPV) and its related pathology. This review will highlight the epidemiology, prevention and treatment of RRP.MethodsThe PubMed database was searched using relevant MeSH terms including "recurrent respiratory papillomatosis." The titles and abstracts were reviewed to assess relevance and unrelated articles were excluded. A full-text review for select articles was performed, the data and discussions were interpreted and synthesized to create a concise update on the management of RRP.ResultsWith the increasing utilization of the 9-valent and quadrivalent HPV vaccine in Australia, we have seen a significant decrease in the incidence of RRP. Preliminary data in the US shows a similar trend of decreased incidence after implementation of vaccination. Single dose Gardasil in developing countries has shown sustained immunization for at least 7 years. Preliminary clinical trials and retrospective studies have shown the HPV vaccine may have benefit as a treatment method in addition to prevention for HPV related diseases. Bevacizumab (Avastin), a VEGF monoclonal antibody, has shown promise as a systemic treatment for RRP. The Corona Virus Disease 2019 (COVID-19) pandemic has affected perioperative management of RRP.ConclusionRRP continues to decline in incidence since the implementation of HPV vaccination. Advancement in the medical management including Bevacizumab show promise as an additional option for the management of RRP.

| S-EPMC8035938 | biostudies-literature

Small RNA next generation sequencing of mice skin biopsies from acetone-treated healthy skins and DMBA/PMA-treated hyperplastic skins, papillomas and cutaneous Squamous Cell Carcinomas

Project description:FVB/N mice were subjected to 7,12-Dimethylbenz[a]anthracene (DMBA) two-hit multistage skin carcinogenesis protocol. Mice were topically treated with 200 nmol of DMBA in 0.2 mL acetone then twice weekly for six weeks with 5 nmol PMA (Phorbol 12-myristate 13-acetate). A second hit of DMBA was performed on the eighth week followed by the resumption of PMA treatment for 14 more weeks. Control mice were only topically treated with 0.2 mL acetone vehicle. Healthy skins (acetone-treated), hyperplastic skins, papillomas and tumors were harvested throughout the protocol and biopsies were frozen for RNA extraction. Small RNA libraries were generated from total RNAs of control skins, hyperplastic skins, papillomas and cSCCs biopsies (n=5 in each group) corresponding to a total of 20 samples, and sequenced on the Applied Biosystems SOLiD System.

2014-02-03 | E-GEOD-52299 | biostudies-arrayexpress

Immune status, strain background, and anatomic site of innoculation affect mouse papillomavirus (MmuPV1) induction of exophytic papillomas or endophytic trichoblastomas

Project description:Papillomaviruses (PVs) are able to induce papillomas, premalignant lesions, and carcinomas in a wide variety of species. PVs are classified first based on their host and tissue tropism and then their genomic diversities. A laboratory mouse papillomavirus, MmuPV1 (formerly MusPV), naturally infects NMRI-Foxn1nu/Foxn1nu (nude; T cell deficient) mice. C57BL/6J wild-type mice were not susceptible to MmuPV1 infection; however, immunocompetent, alopecic, S/RV/Cri-ba/ba (bare) mice developed small papillomas at injection sites that regressed. NMRI-Foxn1nu and B6.Cg-Foxn1nu but not NU/J-Foxn1nu mice were susceptible to MmuPV1 infection. B6 congenic strains, but not other congenic strains carrying the same allelic mutations, that lack B- and T-cells, but not B-cells alone, were susceptible to infection, indicating that mouse strain and T-cell deficiency are critical to tumor formation. Although lesions initially observed were exophytic papillomas around the muzzle, exophytic papillomas on the tail and condylomas of the vaginal lining could be induced by experimental infections. On the dorsal skin, locally invasive, poorly differentiated tumors developed with features similar to human trichoblastomas. Transcriptome analysis revealed significant differences between the normal skin in these anatomic sites and in papillomas versus trichoblastomas. The primarily dysregulated genes involved molecular pathways associated with cancer, cellular development, cellular growth and proliferation, cell morphology, and connective tissue development and function. Surprisingly, few of the genes commonly associated with basal cell carcinoma or squamous cells carcinoma were dramatically dysregulated.

2014-10-28 | GSE58094 | GEO

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