Identification of kidney transplant patients at risk for cutaneous squamous cell carcinoma by differentially methylated regions in T cells (II)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE117050 | GEO | 2018/07/13
REPOSITORIES: GEO
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Project description:We aim to discover differentially methylated regions (DMRs) in peripheral T cells involved in de novo cSCC development after kidney transplantation. This was a retrospective study on biobank patient material. We matched kidney transplant patients with (future) cSCC to those without cSCC and studied genome-wide DNA methylation (450k arrays) of T cells before transplantation.
2017-09-16 | GSE103911 | GEO
Project description:Diabetes mellitus (DM) after transplantation remains a crucial clinical problem in kidney transplantation. To obtain insights into molecular mechanisms underlying the development of post-transplant diabetes mellitus (PTDM) and its early impact on glomerular structures, here we comparatively analyze the proteome of histologically normal appearing glomeruli from patients with PTDM from normoglycemic (NG) transplant recipients, and from recipients with pre-existing type 2 DM (PTDM)
2023-10-24 | PXD042188 | Pride
Project description:The goal is to identify new molecules implicated in tolerance, to determine the implication of these molecules in immune responses to transplantation by gene expression comparison of 27,088 individual rat genes between tolerated kidney allotransplant and syngeneic kidney transplant. In this study 27,088 individual rat genes expression from total mRNA of 3 tolerated allogeneic kidney transplants by anti-classII, were compared to 3 syngeneic kidney transplants at day 100 post transplantation.
2011-04-09 | E-GEOD-28474 | biostudies-arrayexpress
Project description:Background: Cutaneous squamous cell carcinomas (cSCC) are among the most common and highly mutated human malignancies, with rising incidence rates. There are limited treatment options for advanced and metastatic cSCC and particularly high-risk groups, such as organ transplant recipients, are in urgent need for strategies to treat aggressive cSCC. We have previously developed a preclinical murine model for cSCC, with remarkably similar histopathology and genetics to human cSCC. Understanding the impact of DNA methylation in cSCC may provide avenues to develop new treatment or prevention strategies. Here, we perform reduced-representation bisulfite sequencing based DNA methylation analysis of a murine cSCC model (6 tumors, 6 controls, 2 independent healthy skin samples) and compare results with publicly available human cSCC methylation data for two cSCC subtypes, stem-cell like and keratinocyte like tumors. Results: Contrasting most cancers, general DNA hypermethylation was previously reported for high-risk human cSCC. Similarly, we found significantly increased average methylation in mouse cSCC as well as in stem-cell like, but not keratinocyte like, human cSCC. Locus specific methylation changes in mouse cSCC often occurred in regions of potential regulatory function, including enhancers and promoters. One differentially methylated region was located in a potential enhancer of the tumor suppressor gene Filip1l and expression of this gene was significantly reduced in mouse tumors and human cSCC cell lines. Furthermore, comparison of differentially methylated genes revealed remarkable similarities between human and mouse cSCC. Conclusion: Our data suggest that, in addition to mutations, deregulation of DNA methylation is an important feature of murine and human cSCC. DNA methylation likely contributes to silencing of tumor suppressor genes, as shown for the Filip1l gene. The similarities between mouse and human cSCC, particularly stem-cell like, highlight the clinical relevance of our model and presents unique opportunities to identify new treatment strategies.
2021-05-26 | GSE151657 | GEO
Project description:Cutaneous squamous cell carcinoma (cSCC) is the second most commonly diagnosed cancer in the United States each year. Despite a generally good prognosis, metastatic cSCC results in over 3500 deaths annually. There are no specifically targeted therapies or biomarkers for metastatic cSCC. To determine whether aberrant microRNA expression occurs in metastatic cSCC which could provide novel targets for therapy or biomarkers for earlier diagnosis or prognosis, microRNA expression profiling was performed in 48 samples including normal skin, primary tumors and metastases. Multiple microRNAs showed differential expression; miR-4286, miR-200a-3p and miR-148-3p showed increased expression and miR-1915-3p, miR-205-5p, miR-4516 and miR-150-5p showed reduced expression in metastatic samples. Several microRNAs previously showing aberrant expressionshown to be aberrantly expressed in primary cSCCs were also observed in this study including miR-100, miR-135b, miR-145, miR-21, and miR-214. In summary, several microRNAs show differential expression between primary and metastatic cSCCs; these may be useful as biomarkers for metastasis or as targets for therapytherapeutic targets. RNA extracted from primary human tissues
2015-02-28 | E-GEOD-57768 | biostudies-arrayexpress
Project description:Cutaneous 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 investigate the transcriptomes of cSCC and actinic keratoses (AK), to elucidate key differences between precursor AK lesions and invasive carcinoma. This study identified 196 genes that are differentially expressed between AK and cSCC, with enrichment for processes including epidermal differentiation, cell migration, cell cycle regulation and metabolism. Gene set enrichment analysis highlighted a key role for the MAPK pathway in the transition from AK to cSCC. Furthermore, the differentiation status of the tumor influenced the gene expression profile, which may have implications for drug sensitivity and response in clinical trials. These data indicate that progression to cSCC is associated with a complex pattern of molecular changes. We have identified relevant pathways involved in this process, in particular that the MAPK pathway may be pivotal to the transition from AK and may represent a potential therapeutic target. RNA was extracted by laser capture microdissection from 10 AK and 30 cSCC, for analysis using the Affymetrix HG U133 Plus 2.0 microarrays. The cSCC samples included a range of histological diagnoses (well differentiated through to poorly differentiatied) from both immunocompetent and immunosuppressed patients.
2014-01-21 | E-GEOD-45216 | biostudies-arrayexpress
Project description:Background: Remote Ischemic Conditioning (RIC) has been proposed as a therapeutic intervention to circumvent the Ischemia/reperfusion injury (IRI) that is inherent to organ transplantation. Using a porcine kidney transplant model, we aimed to decipher the subclinical molecular effects of a RIC regime, compared to non-RIC controls. Methods: Kidney pairs (n = 8+8) were extracted from brain dead donor pigs and transplanted in juvenile recipient pigs following a period of cold ischemia. One kidney in each pair was subjected to RIC prior to reperfusion, while the other served as non-RIC control. We designed an advanced integrative -Omics strategy combining transcriptomics, proteomics, and phosphoproteomics to deduce molecular signatures in kidney tissue that could be attributed to RIC. Results: In kidney grafts taken out 10 h after transplantation we detected minimal molecular perturbations following RIC compared to non-RIC at the transcriptome level, but more pronounced effects at the proteome level. In particular, we noted that RIC resulted in response suppression of tissue inflammatory profiles. Furthermore, an accumulation of muscle extracellular matrix assembly proteins in RIC tissues was detected at the protein level, which may result in response to muscle tissue damage and/or fibrosis. Conclusions: Our data identifies subtle molecular phenotypes in porcine kidneys subjected to RIC which could aid further optimisation of remote ischaemia protocols in renal transplantation.
2022-04-04 | PXD025273 | Pride
Project description:The expression of lncRNAs in cutaneous squamous cell carcinoma (cSCC) were determined with a commercially available microarray (Arraystar Inc.,Rockville, Maryland USA). The Arraystar human lncRNA Microarray V3.0 containing 30,586 LncRNAs and 26,109 coding transcripts (mRNAs) A total of three patients with cSCC were biopsied. A total of three control (non-lesional skin) were biopsied.
2016-04-13 | E-GEOD-74859 | biostudies-arrayexpress
Project description:The role of itraconazole in cSCC was still unclear. Our objective is to explore the therapeutic potential of itraconazole in cSCC and investigate its molecular mechanism. We proved itraconazole inhibits the growth of cSCC by several pathways.
2022-01-25 | GSE191037 | GEO
Project description:Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer characterized by increased mortality. Here, we show for the first time that anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase of the insulin receptor superfamily, plays a pivotal role in the pathogenesis of cSCC. Our data demonstrate that the overexpression of the constitutively active, mutated ALK, ALKF1174L is sufficient to initiate the development of cSCC and is 100% penetrant. Moreover, we show that cSCC development upon ALKF1174L overexpression is independent of the cell-of-origin. Molecularly, our data demonstrate that ALKF1174L cooperates with oncogenic KrasG12D and loss of p53, well established events in the biology of cSCC. This cooperation results in a more aggressive cSCC type associated with a higher-grade histological morphology. Finally, we demonstrate that Stat3 is a key downstream effector of ALKF1174L and is indispensable for ALKF1174L-driven cSCC tumorigenesis. In sum, these findings reveal that ALK can exert its tumorigenic potential via cooperation with multiple pathways crucial in the pathogenesis of cSCC. Finally, we show that human cSCCs contain mutations in the ALK gene. Taken together, our data identify ALK as a new key player in the pathogenesis of cSCC and this knowledge suggests that oncogenic ALK signaling can be a target for future clinical trials.
2020-04-15 | GSE147642 | GEO