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September 07, 2023
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RNA-sequencing, spatial transcriptomics trace ‘aggressive behavior’ in SCC

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Key takeaways:

  • Patients across several cancer types have worse survival outcomes.
  • The authors hypothesize that this may explain lower survival in organ transplant recipients.

Single-cell RNA-sequencing and spatial transcriptomics may be able to identify tumor-specific keratinocyte subpopulations that mark aggressive squamous cell carcinoma in at-risk patients, according to a review.

“We have previously discovered a subpopulation of tumor cells in skin squamous cell carcinoma (SCC) tumors that have invasive properties and are linked to worse prognosis,” Andrew L. Ji, MD, of the department of dermatology at the Icahn School of Medicine at Mount Sinai, told Healio.

Squamous Cell Carcinoma
Single-cell RNA-sequencing and spatial transcriptomics may be able to identify tumor-specific keratinocyte subpopulations that mark aggressive squamous cell carcinoma in at-risk patients. Image: Adobe Stock.

In their current review assessing how combining single-cell RNA-sequencing (scRNA-seq) and spatial transcriptomics (ST) can influence skin disease treatment and potentially serve as clinical tools, Ji and colleagues included a 2020 study in which Ji and his fellow researchers integrated scRNA-seq and ST from both normal and cutaneous SCC tissue to identify a tumor-specific keratinocyte (TSK) subpopulation found on the leading edge of tumors that orchestrate tumor-stroma interactions.

Andrew L. Ji

In this study, the researchers anticipated that b1-integrin ligands that are expressed by neighboring cancer-associated fibroblasts, macrophages and endothelial cells would signal to TSKs. Furthermore, the scoring for the TSK signature across additional epithelial cancer types indicated the overall survival rate of patients with higher TSK scores was associated with worse survival outcomes.

As a result, Ji and his colleagues believed that measuring the abundance of TSKs may help predict prognosis, particularly in at-risk populations such as organ transplant recipients (OTRs).

“We believe they may explain the more aggressive behavior observed in SCC in the OTR patient population, and we hypothesize that SCC tumors in OTRs harbor more of this subpopulation, potentially through communication with surrounding non-malignant cells,” Ji said. “By identifying this subpopulation and characterizing their behavior further, including how they communicate with surrounding neighboring cells, we aim to identify therapeutic strategies to target this particular subpopulation.”

Vital for discovering new therapeutic strategies is the use of scRNA-seq and ST, according to Ji. Both tools can be used to understand resistance mechanisms in unresponsive patients with inflammatory skin diseases or to stratify the risk for melanoma progression in patients with skin cancer.

According to Ji and his colleagues, continued technical improvements and standardizations of these tools will eventually allow for them to be included in clinical trials and, ultimately, in prognostic guidelines.