The poor clinical outcome and prognosis of esophageal squamous cell carcinoma (ESCC) is mainly attributed to its highly invasive and metastatic nature, making it urgent to further elicit the molecular mechanisms of the metastasis of ESCC. The function of each polycomb chromobox (CBX) protein in cancer is cell-type-dependent. Although CBX8 has been reported to promote the esophageal squamous cell carcinoma (ESCC) tumorigenesis, its role in ESCC metastasis has not been explored yet. In this study, we report that the inhibition of cell migration, invasion, and metastasis in ESCC requires CBX8-mediated repression of Snail, a key transcription factor that induces epithelial-to-mesenchymal transition (EMT), and that CBX8 inversely correlated with Snail in the ESCC tissues. Moreover, this novel function of CBX8 is dependent on its binding with the Snail promoter, which in turn suppresses the transcription of Snail. Collectively, CBX8 may play paradoxical roles in ESCC, inhibiting metastasis while promoting cell proliferation.
Background
The tumor microenvironment plays an essential role in the therapeutic response to immunotherapy. It is necessary to identify immune cell infiltration (ICI) subtypes for evaluating prognosis and therapeutic benefits. This study aimed to evaluate the ICI score as an effective prognostic biomarker for immune response.
Methods
The cell-type identification by estimating relative subsets of RNA transcripts and the estimation of stromal and immune cells in malignant tumors using expression methods were used to analyse ICI landscapes in 161 colorectal cancer (CRC) samples with patients’ clinical and prognostic data, RNA sequencing data, and whole-exome sequencing data from the Sixth Affiliated Hospital, Sun Yat-sen University (Guangzhou, China). Statistical analysis and data processing were conducted to calculate ICI scores, and to analyse the prognosis of CRC patients with different ICI scores and other features. A similar analysis with RNA sequencing and clinical data of colon adenocarcinoma (COAD) samples from The Cancer Genome Atlas (TCGA) database was conducted to confirm the correctness of the findings.
Results
The high-ICI score group with a better prognosis (hazard ratio [HR], 2.19; 95% confidence interval [CI], 1.03–4.64; log-rank test, P = 0.036) was characterized by the increased tumor mutational burden and interleukin-17 (IL-17) signaling pathway. Significant differences in the prognosis and the expression levels of immune checkpoints and chemokine marker genes were found between the two ICI score groups. For COAD samples from TCGA, the results also showed a significant difference in patients’ prognosis between the two ICI score groups (HR, 1.72; 95% CI, 1.00–2.96; log-rank test, P = 0.047).
Conclusions
Tumor heterogeneity induced differences in identifying ICI subtypes of CRC patients. The ICI score may serve as an effective biomarker for predicting prognosis, help identify new therapeutic markers for CRC, and develop novel effective immune checkpoint blockade therapies.
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