Dataset Information

Effect of subcutaneous fat (SF) loss on gene expression with clear cell renal cell carcinoma

ABSTRACT: RCC is one of known malignancies in terms of the association between body mass index (BMI), adiposity, and prognosis, showing overall survival (OS) improvement in obese patients. Despite of increasing interest in this unexpected survival benefit of obesity, termed the “obesity paradox”, previous studies focused on the baseline features without considering their changes. Given that these changes, especially for rapid loss of adipose tissue, are also reported to have a prognostic value in cancer patients, and that ICI therapy can lead to substantial change in body composition, it may be reasonable to assume that these changes are also associated with patient prognoses. However, its prognostic impact on patients with metastatic ccRCC undergoing ICI therapy has not been established. In this study, We investigated the association between these changes and molecular features by targeted sequencing and RNA sequencing of tumor samples to understand the underlying biology.

ORGANISM(S): Homo sapiens

PROVIDER: GSE215286 | GEO | 2022/10/15

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Immunotherapies, including immune checkpoint inhibitors (ICI), have revolutionized the treatment of many cancers, producing significant improvements in survival in patients with many different cancers. However, the intended anti-tumor effects also result in a unique form of autoimmunity, known as immune-related adverse events (irAEs), which have emerged as a limiting factor for many immunotherapies. Cutaneous irAEs (cirAEs), the most frequently occurring ICI–related toxicities, have been associated with improved efficacy and survival but, in their severe forms, require systemic steroids and have in cases led to premature ICI discontinuation and fatality. There is a need for both robust biomarkers and adequate models that effectively predict which patients who develop irAEs may have improved outcomes. Using a microfluidic droplet technology that generates "mini" patient-derived organoids called MicroOrganoSpheres (MOSTM), we successfully generated skin MOS from skin biopsy samples in both healthy skin and tumor-involved skin that sustain the original patient skin immune microenvironment over three weeks. Using this model, we assessed skin cell toxicity and cytokine release in response to ICI and targeted therapies. Clinical responses were largely consistent with the skin and tumor MOS assay readouts, indicating that MOS recapitulates the potential association between skin irAEs and efficacy. Matched pairs of patient melanoma and skin MOS showed good concordance with patient outcome indicating that MOS recapitulates the potential association between skin irAEs and efficacy. Enrichment of genes associated with atopic dermatitis, vitiligo, and psoriatic dermatitis were observed in MOS generated from skin of an ICI-sensitive patient compared to the MOS generated from skin of an ICI-resistant patient. These results indicated that the skin MOS platform can potentially predict the dermatological toxicity of ICI. As the MOS assay can be completed within 12 days after biopsy acquisition, this novel technology may enable personalized medicine approaches by prediction of cirAEs and efficacy for individual patients.

Dataset Information

Effect of subcutaneous fat (SF) loss on gene expression with clear cell renal cell carcinoma

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets