Project description:Genome wide DNA methylation profiling in cutaneous squamous cell carcinoma. The Infinium MethylationEPIC BeadChips 850K has been used to interrogate DNA methylation changes. The cohort included 23 patients in total, with precursors of squamous cell carcinoma (actinic keratosis group) and with cSCC at different stages.
Project description:Analysis of the combined dataset of normal skin, actinic keratosis and cutaneous squamous cell carcinoma (cSCC) previously submitted in (GSE45216) at genomic/transciptomic level. We identified potential cSCC driver genes significantly mutated and upregulated in cSCC relative to normal skin.
Project description:normal skin (no), actinic keratosis (ak), and squamous cell carcinoma (scc) of the skin were examined:; BACKGROUND: Carcinogenesis is a multi-step process indicated by several genes up- or down-regulated during tumor progression. This study examined and identified differentially expressed genes in cutaneous squamous cell carcinoma (SCC). RESULTS: Three different biopsies of 5 immunosuppressed organ-transplanted recipients each normal skin (all were pooled), actinic keratosis (AK) (two were pooled), and invasive SCC and additionally 5 normal skin tissues from immunocompetent patients were analyzed. Thus, total RNA of 15 specimens were used for hybridization with Affymetrix HG-U133A microarray technology containing 22,283 genes. Data analyses were performed by prediction analysis of microarrays using nearest shrunken centroids with the threshold 3.5 and ANOVA analysis was independently performed in order to identify differentially expressed genes (p < 0.05). Verification of 13 up- or down-regulated genes was performed by quantitative real-time reverse transcription (RT)-PCR and genes were additionally confirmed by sequencing. Broad coherent patterns in normal skin vs. AK and SCC were observed for 118 genes. CONCLUSION: The majority of identified differentially expressed genes in cutaneous SCC were previously not described.
Project description:Cutaneous squamous cell carcinoma (SCC) is known for its stepwise progression from healthy skin to premalignant actinic keratosis (AK), followed by malignant transformation into SCC. The main aim is to capture and compare gene expression patterns as AK progresses to SCC.
2025-06-16 | GSE278935 | GEO
Project description:Targeted deep sequencing reveals genomic differences between actinic keratosis and cutaneous squamous cell carcinoma
Project description:Actinic keratosis is a common skin disease that may progress to invasive squamous cell carcinoma. Ingenol mebutate has demonstrated efficacy in field treatment of actinic keratosis. However, molecular mechanisms on ingenol mebutate response are not yet fully understood.
Project description:Squamous cell carcinoma is the second most common skin cancer and frequently progress from an intraepithelial actinic keratosis. The role of microRNAs during the progression from actinic keratosis to cutaneous squamous cell carcinoma (cSCC) remains to be elicited. By using an Agilent microRNA expression microarray we found the expression of miR-204 to be markedly downregulated in cSCC when compared to actinic keratoses. DNA methylation of the TRPM3 promoter region upstream of miR-204-5p was identified as one of the repressive mechanisms that accounts for miR-204 silencing in cSCC. Functional studies on HaCaT cells revealed that this microRNA downregulates the Signal Transducer and Activator of Transcription 3 (STAT3) pathway and favours the MAPK signaling pathway, likely acting through PTPN11, a tyrosine phosphatase that is a direct miR-204 target. We found that activated STAT3, as detected by pY705-STAT3 immunofluorescence, is retained in the membrane and cytoplasm compartment in AK, whereas cSCC displayed STAT3 in the nuclei. Taken together, our data indicates that MiR-204 may act as a “rheostat” that controls the signaling towards the MAPK pathway or the STAT3 pathway.
Project description:Purpose: Primary cutaneous squamous cell carcinoma (SCC) can be an invasive cancer in skin and has the potential to metastasize. We aimed to define the cancer related molecular changes that distinguish non-invasive from invasive SCC. Experimental design: We used laser capture microdissection technique in combination with cDNA microarray analysis in order to determine molecular changes that associate with SCC progression. Results: We defined invasion-associated genes as those udifferentially regulated only in SCC invasive nests, but not in actinic keratosis-like dysplasia or SCC in situ regions, compared to normal epidermis. We designated these genes as “invasion signature gene set of cutaneous SCC”. Overall we found 383 up- and 354 down-regulated probe-sets that constitute the invasion signature gene set. As part of this profile, SCC invasion is associated with aberrant gene expression changes of numerous MMPs including MMP7 (FCH=5.43, FDR<0.01) and MMP13 (FCH=12.53, FDR<0.01). IL-24 is also up-regulated in the leading invasive edge of SCC (FCH=6.74, FDR<0.01). IL-24 enhanced mRNA expression of both MMP7 and MMP13 in a human SCC cell line. Laminin332, which is one of the target molecules of MMP7, had altered expression at the leading edge of SCC invasion nests at both the genomic and protein level. Conclusions: We defined the distribution of MMPs within human cutaneous SCC tissue showing distinct expression with progression from normal skin to actinic keratosis to SCC in situ to invasive carcinoma. We further suggest a potential role for IL-24 in progression to invasion via MMP7 and MMP13. Laser capture microdissection was performed on 5 cases of actinic keratosis, 5 cases of in situ SCC, and 5 cases of invasive SCC.
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.
Project description:This study used non-invasive sampling by tape-stripping coupled with data-independent acquisition mass spectrometry (DIA-MS) proteomics to profile the proteome of 61 histopathologically diagnosed Keratinocytic skin lesions (KSLs), including pre-malignant actinic keratosis (AK) and Bowen's disease (BD), and invasive cutaneous squamous cell carcinoma (cSCC)as well as matched normal stratum corneum samples collected from 26 patients.
