Subtype specific analyses reveal Infiltrative Basal Cell Carcinoma are highly interactive with their environment
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE156171 | GEO | 2021/04/19
REPOSITORIES: GEO
Similar Datasets
Project description:Basal cell carcinomas (BCCs) are the most common cancers in the US. Histologic appearance distinguishes several subtypes, each of which can have a different biologic behavior. In this study global miRNA expression was quantified by high throughput sequencing in nodular BCCs, a subtype that is slow growing, and infiltrative BCCs, aggressive tumors that extend through the dermis and invade structures such as cutaneous nerves. Principal components analysis correctly classified seven out of eight infiltrative tumors on the basis of miRNA expression. The remaining tumor, on pathology review, contained a mixture of nodular and infiltrative elements. Nodular tumors did not cluster tightly, likely reflecting broader histopathologic diversity in this class, but trended toward forming a group separate from infiltrative BCCs. qPCR assays were developed for six of the miRNAs that showed significant differences between the BCC subtypes, and five of these six were validated in a replication set of four infiltrative and three nodular tumors. The expression level of miR-183, a miRNA that inhibits invasion and metastasis in several types of malignancies, was consistently lower in infiltrative than nodular tumors and could be one element underlying the difference in invasiveness. These results represent the first miRNA profiling study in BCCs and demonstrate that miRNA gene expression may be involved in tumor pathogenesis and particularly in determining the aggressiveness of these malignancies. Total RNA was extracted from eight nodular and eight infiltrative basal cell carcinomas. miRNA was then processed into libraries using the Illumina Small RNA Ver 1.5 protocol. Samples were then sequenced on the Illumina GAII system
2012-02-01 | E-GEOD-33665 | biostudies-arrayexpress
Project description:In summary, we have validated differential expression of several miRs, namely two that are downregulated in all BCC subtypes compared to control skin (miR.383.5p, miR.145.5p), two that are downregulated in superficial BCC (miR.181c.5p, miR.181b.5p) relative to nodular and infiltrative BCC, and several that are upregulated in infiltrative BCC relative to superficial BCC (miR.22.5p, miR.18a.3p, miR.708.5p, miR.758.3p, miR.30c.5p), and two that are upregulated in infiltrative BCC relative to nodular BCC (miR.22.5p, miR.758.3p). To our knowledge, this study has investigated and validated the largest number of BCC tumors representing the different subtypes.
2024-01-01 | GSE245676 | GEO
Project description:Basal cell carcinomas (BCCs) are the most common cancers in the US. Histologic appearance distinguishes several subtypes, each of which can have a different biologic behavior. In this study global miRNA expression was quantified by high throughput sequencing in nodular BCCs, a subtype that is slow growing, and infiltrative BCCs, aggressive tumors that extend through the dermis and invade structures such as cutaneous nerves. Principal components analysis correctly classified seven out of eight infiltrative tumors on the basis of miRNA expression. The remaining tumor, on pathology review, contained a mixture of nodular and infiltrative elements. Nodular tumors did not cluster tightly, likely reflecting broader histopathologic diversity in this class, but trended toward forming a group separate from infiltrative BCCs. qPCR assays were developed for six of the miRNAs that showed significant differences between the BCC subtypes, and five of these six were validated in a replication set of four infiltrative and three nodular tumors. The expression level of miR-183, a miRNA that inhibits invasion and metastasis in several types of malignancies, was consistently lower in infiltrative than nodular tumors and could be one element underlying the difference in invasiveness. These results represent the first miRNA profiling study in BCCs and demonstrate that miRNA gene expression may be involved in tumor pathogenesis and particularly in determining the aggressiveness of these malignancies.
2012-02-01 | GSE33665 | GEO
Project description:Ampullary adenocarcinoma (AAC) is a rare gastrointestinal cancer with varying survival rates, particularly the aggressive pancreatobiliary (PB) subtype. Adjuvant therapy benefits only PB and mixed subtype patients, while prospective studies are required for validation. A study proposes tailored adjuvant treatments (CAPOX for intestinal subtype, FOLFIRINOX for PB and mixed subtypes) based on histopathology to enhance survival, also exploring molecular sub-studies for deeper insights.
| 108044 | ecrin-mdr-crc
Project description:Background: Vulvar squamous cell carcinoma (vSCC) is a rare but debilitating disease. One vSCC subtype comprises tumor cells that grow and expand as a cohesive sheet of cells that “pushes” and compresses the associated lymphoplasmacytic (LPC) stroma. Another vSCC subtype features tumor cells that grow in loose association with other tumor cells and infiltrate the associated fibromyxoid (FMX) stroma consisting mainly of extracellular matrix. Clinically, infiltrative vSCC with FMX stroma (Inf/FMX) is significantly associated with lymph node metastases and recurrence. Methods: An unbiased proteomic approach was used to identify pathways that could produce these different vSCC subtypes. Formalin-fixed and paraffin-embedded tissues from 10 cases of pushing vSCC with LPC stroma (Push/LPC) and 8 cases of Inf/FMX were subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Analysis identified 2,265 different proteins in the 18 samples of vSCC. Of these, 344 proteins were differentially expressed (p<0.05) by at least 4-fold between vSCC subtypes. Of these, 59 were higher and 285 lower in Inf/FMX compared to Push/LPC tumors. Consistent with the desmoplastic morphology and increased picrosirius red staining, expression of subunits of several collagens (Col 1, 3, 6, 14, 18) was higher in the more aggressive Inf/FMX tumors. In contrast, signal transducer and activator of transcription 1 (STAT1), an important regulator of several inflammatory pathways, was expressed at lower levels in the Inf/FMX tumors. This finding was confirmed by immunohistochemistry using an antibody to STAT1. An informatics analysis of the differing profiles identified differences in the integrin signaling pathway and inflammation mediated by chemokine and cytokine signaling pathway. This analysis also linked decreased expression of proteins involved antigen processing and presentation and increased expression of those with cell-matrix adhesion as processes with the more aggressive Inf/FMX vSCC subtype. Conclusions: Comparing the proteomic profiles of vSCC morphologic subtypes indicates that increased expression of collagen subunits and decreased expression of STAT1 are associated with a more aggressive tumor subtype. Informatic analyses further identify alterations in cell interaction with matrix and immune function differ with tumor aggressiveness. Identification of these pathways provides a molecular basis for understanding aggressiveness of vSCC.
2017-12-12 | PXD006901 | Pride
Project description:Non-melanoma skin cancers (NMSC) including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are more common kinds of skin cancer. Although these tumors share common pathological and clinical features, their similarity and heterogeneity at molecular levels are not fully elaborated yet. Here, by performing comparative analysis of gene expression profiling of BCC, SCC, and normal skin tissues, we could classify the BCC into three subtypes of classical, SCC-like, and normal-like BCCs. Functional enrichment and pathway analyses revealed the molecular characteristics of each subtype. The analysis of gene expression profiling among non-melanoma skin cancer types
2014-12-13 | E-GEOD-53462 | biostudies-arrayexpress
Project description:Non-melanoma skin cancers (NMSC) including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are more common kinds of skin cancer. Although these tumors share common pathological and clinical features, their similarity and heterogeneity at molecular levels are not fully elaborated yet. Here, by performing comparative analysis of gene expression profiling of BCC, SCC, and normal skin tissues, we could classify the BCC into three subtypes of classical, SCC-like, and normal-like BCCs. Functional enrichment and pathway analyses revealed the molecular characteristics of each subtype.
2014-12-13 | GSE53462 | GEO
Project description:Subtype specific analyses reveal Infiltrative Basal Cell Carcinoma are highly interactive with their environment
| PRJNA656960 | ENA
Project description:Breast cancer is no longer viewed as a homogenous disease, but rather a compilation of several distinct subtypes as defined by microarray or other large scale genomic analyses. Based on prior reports, we hypothesized that younger women’s breast tumors would be enriched for more aggressive subtypes (i.e. Basal-like) and higher grade, and that age-specific gene expression differences may be highly dependent on subtype classification and/or grade. Using two independent datasets, our current analysis shows that breast tumors arising in women aged = 45 years are enriched for the Basal-like subtype (and higher grade) while those aged = 65 years are enriched for Luminal tumors. Moreover, when evaluating gene expression differences between age-defined groups, sizable gene lists were identified which diminished to few, if any, age-specific genes when statistically correcting for significant clinical factors (i.e. subtype, grade, etc). Keywords: reference x sample 344 breast tumor samples hybridized with Stratagene common reference and profiled on Agilent microarrays.
2010-08-31 | E-GEOD-20624 | biostudies-arrayexpress
Project description:Background; Basal cell carcinoma (BCC) is the most common cancer in humans. The pathogenesis of BCC is associated with the sonic hedgehog (SHH) signaling pathway. Vismodegib, a smoothened inhibitor, that targets this pathway is now in clinical use for advanced BCC patients, but its efficacy is limited. Therefore, new therapeutic options for this cancer are required. Methods; We studied gene expression profiling of BCC tumour tissue coupled with laser capture microdissection to identify tumor specific receptor tyrosine kinase expression that can be targeted by small molecule inhibitors. The expression of selected molecules was confirmed by quantitative RT-PCR (qRT-PCR) and by immunohistochemistry. The action of kinase inhibitors was examined on primary normal human epidermal keratinocytes. Results; We found a >250 fold change increase (false discovery rate <10-4) of the oncogene, anaplastic lymphoma kinase (ALK) as well as its ligands, pleiotrophin and midkine in BCC compared to microdissected normal epidermis. qRT-PCR confirmed increased expression of ALK (p<0.05). Stronger staining of phosphorylated ALK in BCC tumour nests than normal skin was observed by immunohistochemistry. Additionally, Crizotinib, an FDA-approved ALK inhibitor, reduced keratinocyte proliferation in culture, whereas a c-Met, another receptor tyrosine kinase, inhibitor did not. Crizotinib significantly reduced the expression of GLI1 and CCND2 mRNA by approximately 60% and 20%, respectively (p<0.05). Conclusions; Our data suggest that ALK may increase GLI1 expression in parallel with the conventional SHH-pathway and promotes keratinocyte proliferation. Furthermore, an ALK inhibitor alone or in combination with targeting SHH-pathway molecules may be a potential treatment for BCC patients. Laser capture microdissection was performed on 5 cases of nodular/superficial BCC, 5 cases of infiltrative BCC.
2013-01-30 | E-GEOD-42109 | biostudies-arrayexpress