Profiles of differentially expressed circRNAs in esophageal and breast cancer

Abstract

Introduction: Circular RNAs (circRNAs) function as efficient microRNA sponges with gene-regulatory potential and are promising cancer biomarkers. In this study, we used the Arraystar Human circRNA Array to construct a genome-wide circRNA profile of esophageal squamous cell cancer (ESCC) and breast cancer (BC).

Patients and methods: Expression levels between cancer lesions and adjacent normal-appearing tissues were compared. We observed 469 upregulated circRNAs and 275 downregulated circRNAs in ESCC. Hsa_circRNA_103670 was upregulated 20.3-fold, while hsa_circRNA_030162 was downregulated 12.1-fold. For BC, 715 circRNAs were upregulated, and 440 circRNAs were downregulated. Hsa_circRNA_005230 was upregulated 12.2-fold, while hsa_circRNA_406225 was downregulated 12.4-fold.

Results: When we set the criteria as fold change in expression ≥2 between cancer and adjacent normal-appearing tissue with a P-value <0.01, there were 22 common circRNAs (11 upregulated and 11 downregulated) in relation to both ESCC and BC. Gene ontology and the Kyoto encyclopedia of genes and genomes analyses showed that these circRNAs were involved in the tumorigenesis of human cancers.

Conclusion: Our study revealed that circRNAs are promising candidates as valuable biomarkers for ESCC and BC, although relevant research is still in its infancy and the functional role of specific circRNAs in tumorigenesis is just starting to be elucidated.

Keywords: biomarker; breast cancer; circRNA; esophageal squamous cell carcinoma; noncoding RNA.

Figure 1

Heat map showing the expression profiles of circRNAs in ESCC (A) and BC (B). Notes: The expression values are represented by the color scale. The intensity increases from green (relatively lower expression) to red (relatively higher expression). Each column represents one tissue sample, and each row represents a single circRNA. C1–C7 represent seven ESCC specimens collected from ESCC patients. N1–N7 represent paired adjacent normal-appearing tissues. C8–C11 represent four BC specimens collected from BC patients. N8–N11 represent paired adjacent normal-appearing tissues. Abbreviations: ESCC, esophageal squamous cell cancer; BC, breast cancer.

Figure 2

Scatter plots demonstrating the heterogeneity of ESCC lesions (A) and BC lesions (B) with their adjacent normal-appearing tissues. Notes: The values of the X and Y axes represent the averaged normalized signal values of the group (log2-scaled). The green line stands for 2-fold changes. The expression of the circRNAs above the top green line and below the bottom green line indicate changes by >2-fold between the two groups of samples. Abbreviations: ESCC, esophageal squamous cell cancer; BC, breast cancer.

Figure 3

Volcano plots visualizing differential expression of ESCC lesions (A) and BC lesions (B) with adjacent normal tissues. Notes: The vertical lines correspond to 2.0-fold up- and downregulation (log2 ratio), and the horizontal line represents a P-value of 0.05. The red points in the plot represent the differentially expressed circRNAs with statistical significance (fold change >2 and P<0.05), the gray points represent the remaining circRNAs (fold change <2 or P>0.05). Abbreviations: ESCC, esophageal squamous cell cancer; BC, breast cancer.