Uncovering Misidentified Cell Identity in Esophageal Cancer
Summary
Here, they show that esophageal squamous cell carcinoma (ESCC) cells have molecular features different from all three types of normal esophageal epithelial cells. They name this "confused cell identity" (CCI), a separate indicator of prognosis that is related to a bad prognosis in ESCC. Also, they find that tropomyosin 4 (TPM4) is a key CCI gene that makes ESCC more aggressive both in the lab and in real life. And CCI is induced by TPM4 by turning on the Jak/STAT-SOX2 pathway. So, their study points to a feature of ESCC cells that hasn't been noticed before, which could be useful for clinical prognosis and possible interference.
Research Criteria
They investigated the cellular identity of ESCC at the level of a single cell in the context of normal epithelial cells using a discovery cohort of seven tumor samples and one distal normal sample from patients with ESCC.
Fig.1 Experimental design. (Pan, 2022)
Sample Type
Human ESCC tumor tissue and normal adjacent tissue.
Result—Single Cell Transcriptomics Reveals CCI as a Unique Identity of ESCC Cells
A total of 44,206 cells, comprising 16,657 normal and malignant cells, were collected. They made a ternary map with the letters BS, BK, and DK at each corner to show the interaction between ESCC tumor cells and healthy epithelial cells. The heatmap of gene expression revealed that ESCC cells displayed all of the distinguishing genes of BS, BK, and DK, albeit at somewhat reduced levels. In line with this, a higher average number of genes were found in malignant cells than in normal ones. This outcome was in opposition to the conventional stem cell theory of cancer. The CCI is what they called this new cell identity in comparison to the normal cells. They created a CCI score to calculate the CCI of each cell on the ternary map. The median CCI score for cancerous cells was 43.2 and 21.2 for normal cells, respectively.
Fig.2 CCI is a feature of ESCC cells at single-cell resolution. (Pan, 2022)
Result—CCI Is a General Feature of ESCC in Multiple Cohorts
The authors then tried to find a relationship between the CCI score and how aggressive ESCC was. First, they saw that the average CCI score was much higher in people with ESCC who were getting worse quickly. Even though there was a difference between and within tumors, the CCI scores of early-stage patients were much lower than those of advanced-stage patients. At the level of a single cell, the CCI scores were always strongly related to the expression of genes that are only found in ESCC in the advanced stage.
Fig.3 CCI is an independent prognostic marker in ESCC. (Pan, 2022)
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Reference
- Pan, X.; et al. Identifying a confused cell identity for esophageal squamous cell carcinoma. Signal Transduction and Targeted Therapy. 2022, 7(1): 1-11.
