RNA-seq of human skin lesions diagnosed as actinic keratosis, intraepidermal carcinoma or squamous cell carcinoma
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 2500
ORGANISM(S): Homo sapiens
SUBMITTER: Samuel Lukowski
PROVIDER: E-MTAB-6430 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Detection of HPV E7 Transcription at Single-Cell Resolution in Epidermis.
Lukowski Samuel W SW Tuong Zewen K ZK Noske Katharina K Senabouth Anne A Nguyen Quan H QH Andersen Stacey B SB Soyer H Peter HP Frazer Ian H IH Powell Joseph E JE
The Journal of investigative dermatology 20180630 12
Persistent human papillomavirus (HPV) infection is responsible for at least 5% of human malignancies. Most HPV-associated cancers are initiated by the HPV16 genotype, as confirmed by detection of integrated HPV DNA in cells of oral and anogenital epithelial cancers. However, single-cell RNA sequencing may enable prediction of HPV involvement in carcinogenesis at other sites. We conducted single-cell RNA sequencing on keratinocytes from a mouse transgenic for the E7 gene of HPV16 and showed sensi ...[more]
Similar Datasets
Project description:The goal of the study is to compare the transcriptomic profile of patient-derived skin samples, Actinic Keratosis, Intraepidermal Carcinoma and Squamous Cell Carcinoma samples using next generation RNA Sequencing. We aim to identify perturbed pathways and similarities between the 4 conditions. Please note that detailed patients' information, such as gender and age, was withheld from this submission to protect the patients' identity.
2017-05-16 | E-MTAB-5678 | biostudies-arrayexpress
Project description:OBJECTIVE:To compare the repetitive DNA patterns of human actinic keratoses and squamous cell carcinomas to determine the genetic alterations that are associated with malignant transformation. INTRODUCTION:Cancer cells are prone to genomic instability, which is often due to DNA polymerase slippage during the replication of repetitive DNA and to mutations in the DNA repair genes. The progression of benign actinic keratoses to malignant squamous cell carcinomas has been proposed by several authors. MATERIAL AND METHODS:Eight actinic keratoses and 24 squamous cell carcinomas (SCC), which were pair-matched to adjacent skin tissues and/or leucocytes, were studied. The presence of microsatellite instability (MSI) and the loss of heterozygosity (LOH) in chromosomes 6 and 9 were investigated using nine PCR primer pairs. Random Amplified Polymorphic DNA patterns were also evaluated using eight primers. RESULTS:MSI was detected in two (D6S251, D9S50) of the eight actinic keratosis patients. Among the 8 patients who had squamous cell carcinoma-I and provided informative results, a single patient exhibited two LOH (D6S251, D9S287) and two instances of MSI (D9S180, D9S280). Two LOH and one example of MSI (D6S251) were detected in three out of the 10 patients with squamous cell carcinoma-II. Among the four patients with squamous cell carcinoma-III, one patient displayed three MSIs (D6S251, D6S252, and D9S180) and another patient exhibited an MSI (D9S280). The altered random amplified polymorphic DNA ranged from 70% actinic keratoses, 76% squamous cell carcinoma-I, and 90% squamous cell carcinoma-II, to 100% squamous cell carcinoma-III. DISCUSSION:The increased levels of alterations in the microsatellites, particularly in D6S251, and the random amplified polymorphic DNA fingerprints were statistically significant in squamous cell carcinomas, compared with actinic keratoses. CONCLUSION:The overall alterations that were observed in the repetitive DNA of actinic keratoses and squamous cell carcinomas indicate the presence of a spectrum of malignant progression.
| S-EPMC3093780 | biostudies-literature
Project description:The purpose of this study was to identify genes involved in the skin immune response that changed expression in response to scabies mite infestation. Transcriptomic analysis was undertaken using total RNA extracted from skin biopsies. Four biological replicates for non-infested control group and eight (four for crusted scabies disease phenotype and four for ordinary scabies diseases phenotype) biological replicates for the mite-infested group were used for gene expression analysis at baseline week 0, and at weeks 1, 2, 4 and 8 post-infestation using A-GEOD-16571 Agilent Porcine Gene Expression Microarray 4 x 44K.
2018-06-11 | E-MTAB-6433 | biostudies-arrayexpress
Project description:Actinic keratoses (AKs) are common skin lesions heralding an increased risk of developing squamous cell carcinoma (SCC) and other skin malignancies, arising principally due to excessive ultraviolet (UV) exposure. They are predominantly found in fair-skinned individuals, and increasingly, are a problem of the immunosuppressed. AKs may regress spontaneously, remain stable or transform to invasive SCC. The risk of SCC increases for those with more than 5 AKs, and the majority of SCCs arise from AKs. The main mechanisms of AK formation are inflammation, oxidative stress, immunosuppression, impaired apoptosis, mutagenesis, dysregulation of cell growth and proliferation, and tissue remodeling. Human papilloma virus has also been implicated in the formation of some AKs. Understanding these mechanisms guides the rationale behind the current available treatments for AKs. One of the main principles underpinning the management of AKs is that of field cancerization. Wide areas of skin are exposed to increasing amounts of UV light and other environmental insults as we age. This is especially true for the head, neck and forearms. These insults do not target only the skin where individual lesions develop, but also large areas where crops of AKs may appear. The skin between lesions is exposed to the same insults and is likely to contain as-yet undetectable preclinical lesions or areas of dysplastic cells. The whole affected area is known as the 'field'. Management is therefore divided into lesion-directed and field-directed therapies. Current therapies include lesion-directed cryotherapy and/or excision, and topical field-directed creams: 5-fluorouracil, imiquimod, diclofenac, photodynamic therapy and ingenol mebutate. Combining lesion- and field-directed therapies has yielded good results and several novel therapies are under investigation. Treatment is variable and tailored to the individual making a gold standard management algorithm difficult to design. This literature review article aims to describe the rationale behind the best available therapies for AKs in light of current understanding of pathophysiology and epidemiology. A PubMed and MEDLINE search of literature was performed between January 1, 2000 and September 18, 2013. Where appropriate, articles published prior to this have been referenced. This is not a systematic review or meta-analysis, but aims to highlight the most up to date understanding of AK disease and its management.
| S-EPMC4065271 | biostudies-literature
Project description:Cutaneous squamous cell carcinoma (SCC) is the second-most-common cancer in Australia. The majority of SCCs progress from premalignant actinic keratosis (AK) lesions that form on chronically sun-exposed skin. The role of skin microbiota in this progression is not well understood; therefore, we performed a longitudinal microbiome analysis of AKs and SCCs using a cohort of 13 SCC-prone immunocompetent men. The majority of variability in microbial profiles was attributable to subject, followed by time and lesion type. Propionibacterium and Malassezia organisms were relatively more abundant in nonlesional photodamaged skin than in AKs and SCCs. Staphylococcus was most commonly associated with lesional skin, in particular, sequences most closely related to Staphylococcus aureus Of 11 S. aureus-like operational taxonomic units (OTUs), six were significantly associated with SCC lesions across seven subjects, suggesting their specific involvement with AK-to-SCC progression. If a causative link exists between certain S. aureus-like OTUs and SCC etiology, therapeutic approaches specifically targeting these bacteria could be used to reduce SCC.IMPORTANCE Actinic keratosis (AK) and cutaneous squamous cell carcinoma (SCC) are two of the most common dermatologic conditions in Western countries and cause substantial morbidity worldwide. The role of human papillomaviruses under these conditions has been well studied yet remains inconclusive. One PCR-based study has investigated bacteria in the etiology of these conditions; however, no study has investigated the microbiomes of AK and SCC more broadly. We longitudinally profiled the microbiomes of 112 AK lesions, profiled cross sections of 32 spontaneously arising SCC lesions, and compared these to matching nonlesional photodamaged control skin sites. We identified commonly occurring strains of Propionibacterium and Malassezia at higher relative abundances on nonlesional skin than in AK and SCC lesions, and strains of Staphylococcus aureus were relatively more abundant in lesional than nonlesional skin. These findings may aid in the prevention of SCC.
| S-EPMC6178618 | biostudies-literature
Project description:In this work, hybrid compounds 1-4 obtained by conjugation of the non-steroidal anti-inflammatory drug diclofenac, with natural molecules endowed with antioxidant and antiproliferative activity were prepared. The antiproliferative activity of these hybrids was evaluated on immortalized human keratinocyte (HaCaT) cells stimulated with epidermal growth factor (EGF), an actinic keratosis (AK) model, and on human squamous cell carcinoma (SCC) cells (A431). Hybrid 1 presented the best activity in both cell models. Self-assembling surfactant nanomicelles have been chosen as the carrier to drive the hybrid 1 into the skin; the in vitro permeation through and penetration into pig ear skin have been evaluated. Among the nanostructured formulations tested, Nano3Hybrid20 showed a higher tendency of the hybrid 1 to be retained in the skin rather than permeating it, with a desirable topical and non-systemic action. On these bases, hybrid 1 may represent an attractive lead scaffold for the development of new treatments for AK and SCC.
| S-EPMC6539072 | biostudies-literature
Project description:Actinic keratoses (AKs) are lesions of epidermal keratinocyte dysplasia and are precursors for invasive cutaneous squamous cell carcinoma (cSCC). Identifying the specific genomic alterations driving the progression from normal skin to skin with AK to skin with invasive cSCC is challenging because of the massive UVR-induced mutational burden characteristic at all stages of this progression. In this study, we report the largest AK whole-exome sequencing study to date and perform a mutational signature and candidate driver gene analysis on these lesions. We demonstrate in 37 AKs from both immunosuppressed and immunocompetent patients that there are significant similarities between AKs and cSCC in terms of mutational burden, copy number alterations, mutational signatures, and patterns of driver gene mutations. We identify 44 significantly mutated AK driver genes and confirm that these genes are similarly altered in cSCC. We identify azathioprine mutational signature in all AKs from patients exposed to the drug, providing further evidence for its role in keratinocyte carcinogenesis. cSCCs differ from AKs in having higher levels of intrasample heterogeneity. Alterations in signaling pathways also differ, with immune-related signaling and TGFβ signaling significantly more mutated in cSCC. Integrating our findings with independent gene expression datasets confirms that dysregulated TGFβ signaling may represent an important event in AK‒cSCC progression.
| S-EPMC8221374 | biostudies-literature
Project description:BackgroundCutaneous squamous cell carcinoma (cSCC) is one of the most common malignancies in fair-skinned populations worldwide and its incidence is increasing. Despite previous observations of multiple genetic abnormalities in cSCC, the oncogenic process remains elusive. The purpose of this study was to elucidate key molecular events associated with progression from premalignant actinic keratoses (AKs) to invasive cSCC by transcriptome profiling.MethodsWe combined laser capture microdissection with the Affymetrix HGU133 Plus 2.0 microarrays to profile 30 cSCC and 10 AKs.ResultsWe identified a core set of 196 genes that are differentially expressed between AK and cSCC, and are enriched for processes including epidermal differentiation, cell migration, cell-cycle regulation and metabolism. Gene set enrichment analysis highlighted a key role for the mitogen activated protein kinase (MAPK) pathway in cSCC compared with AK. Furthermore, the histological subtype of the tumour was shown to influence the expression profile.ConclusionThese data indicate that the MAPK pathway may be pivotal to the transition from AK to cSCC, thus representing a potential target for cSCC prevention. In addition, transcriptome differences identified between cSCC subtypes have important implications for future development of targeted therapies for this malignancy.
| S-EPMC3899778 | biostudies-literature
Project description:ImportanceActinic keratosis (AK), a skin growth induced by ultraviolet light exposure, requires chronic management because a small proportion can progress into squamous cell skin cancer. Spending for AK management was more than $1 billion in 2004. Investigating geographic variation in AK spending presents an opportunity to decrease waste or recoup excess spending.ObjectiveTo evaluate geographic variation in health care cost for management of AKs and the association with patient-related and health-related factors.Design, setting, and participantsThis retrospective cohort study was performed using data from the MarketScan medical claims database of 488 324 continuously enrolled members with 2 or more claims for AK. Data from January 1, 2008, to December 31, 2012, was used.Main outcomes and measuresAnnual costs of care were calculated for outpatient visits, AK destruction, and medications for AKs, and the total of these components. Costs were adjusted for inflation to 2014 US dollars. To display cost variation, we calculated the ratio of mean cost in the highest quintile (Q5) relative to the mean in the lowest quintile (Q1), or the Q5:Q1 ratio; Q5:Q1 ratios were adjusted based on age, sex, history of nonmelanoma skin cancer, US geographic region, and population density (metropolitan statistical area).ResultsOverall, data from 488 324 continuously enrolled members (mean [SD] age, 53.1 [7.5] years; 243 662 women) with 2 or more claims for AK were included. Overall, patients had 1 085 985 claims related to AK, and dermatologists accounted for 71.0% of claims. The 2-year total cost was $111.5 million, with $52.4 million in 2011 and $59.1 million in 2012. The unadjusted Q5:Q1 ratios for total annual cost per patient ranged from 9.49 to 15.10. Adjusted ratios ranged from 1.72 to 1.80.Conclusions and relevanceThere is variation in AK management cost within and between regions. This is not fully explained by differences in patient characteristics such as age, sex, or comorbidities. The annual cost for 10 common conditions from Medicare had lower Q5:Q1 ratios that ranged from 1.33 (joint degeneration of back/neck) to 1.69 (chronic sinusitis) when compared with 1.72 to 1.80 for AKs. This suggests an opportunity to investigate and improve the value of health care delivery in the management of AKs.
| S-EPMC5470414 | biostudies-literature
Project description:BackgroundActinic keratoses (AK) are pre-malignant cutaneous lesions caused by prolonged exposure to ultraviolet radiation. As AKs lesions are generally accepted to be the initial lesions in a disease continuum that progresses to squamous cell carcinoma (SCC), AK lesions have to be treated. They are also the second most common reason for visits to the dermatologist. Several treatments are available but their efficacy still needs to be improved. The UV-B-induced KA lesion mouse model is used in preclinical studies to assess the efficacy of novel molecules, even though it is often more representative of advanced AK or SCC.ObjectivesHere we report on a translational study, comparing the various stages of AK development in humans and in the UV-B irradiated mouse model, as well as the optimization of photograph acquisition of AK lesions on mouse skin.MethodsHuman and mouse skin lesions were analysed by histology and immunohistochemistry. Mouse lesions were also assessed using a digital dermatoscope.ResultsAn histological and phenotypic analysis, including p53, Ki67 and CD3 expression detection, performed on human and mouse AK lesions, shows that overall AK modelling in mice is relevant in the clinical situation. Some differences are observed, such as disorganization of keratinocytes of the basal layer and a number of atypical nuclei which are more numerous in human AK, whereas much more pronounced acanthosis is observed in skin lesion in mice. Thanks to this translational study, we are able to select appropriate experimental conditions for establishing either early or advanced stage AK or an SCC model. Furthermore, we optimized photograph acquisition of AK lesions on mouse skin by using a digital dermatoscope which is also used in clinics and allows reproducible photograph acquisition for further reliable assessment of mouse lesions. Use of this camera is illustrated through a pharmacological study assessing the activity of CARAC®.ConclusionThese data demonstrate that this mouse model of UV-B-induced skin lesions is predictive for the identification of novel therapeutic treatments for both early and advanced stages of the disease.
| S-EPMC5491107 | biostudies-literature