Altered Expression of Survivin Variants S-2B and S-WT in Breast Cancer Is Related to Adipokine Expression

Abstract

Breast cancer (BCa) is one of the leading causes of death in women with these types of malignancies. Early detection is pivotal to improve prognosis and reduce mortality. Several proteins and genes have been proposed as biomarkers for cancer; however, further studies are required before a molecule is accepted as a definitive biomarker. This study was aimed at investigating the expression of survivin variants S-WT, S-2B, and S-ΔEx3, as well as adipokines LEP and ADIPOQ in breast cancer. Breast samples were obtained from patients with (n = 27) and without (n = 20) BCa, and relative gene expression was assessed by RT-qPCR. S-WT and S-2B showed a significant increase in BCa samples (p = 0.005 and p = 0.001, respectively) and in high-aggressiveness BCa (p = 0.026 and p = 0.037, respectively). Despite S-ΔEx3 expression remained globally unchanged, when dividing BCa samples according to the stage, this gene showed a significant tendency to increase towards more advanced stages, and the exact opposite effect was observed for LEP. Furthermore, LEP expression showed a negative correlation with S-2B (p = 0.005) and S-WT (p = 0.011), and in the same manner, ADIPOQ was negatively related with these two survivin variants (p = 0.001 and p = 0.005, respectively). Interestingly, S-ΔEx3 expression appears unaffected by LEP and ADIPOQ expressions. Our results highlight the importance of investigating specific variants of a given gene, as sequence variation may grant different correlation with other important structures and diseases.

Figure 1

Relative expression of S-WT, S-2B, S-ΔEx3, LEP, and ADIPOQ. Relative expression was compared between groups using the number of samples described for each gene in the result section. RT-qPCR exhibited significantly higher expression levels of S-WT and S-2B in BCa patients. Our results did not show a significant difference in the expression of S-ΔEx3, LEP, and ADIPOQ between groups. Bars represent mean values ± SD. ^∗∗p < 0.01.

Figure 2

Relative expression of S-WT, S-2B, S-ΔEx3, LEP, and ADIPOQ in different BCa stages. Relative expression was compared among stages using the number of samples described for each gene in Table 2. Early stage patients exhibited the highest LEP expression (IA = 11.49), and late stage patients showed the lowest expression levels (IIIB = 0.05). On the other hand, we found the lowest S-ΔEx3 expression in patients with low-grade tumors (IA = 0.14) and a gradual increase, until reaching the highest expression in stage IIIB (15.39). Bars represent mean values ± SD. ^∗p < 0.05.

Figure 3

Relative expression of S-WT, S-2B, S-ΔEx3, LEP, and ADIPOQ in different BCa aggressiveness. Low-aggressiveness BCa subtypes luminal A, B, and HER2 are included in the luminal group, and high-aggressiveness BCa subtypes HER2-enriched and Basal-like are included in the HER2-basal group. Results showed a significant overexpression of S-WT and S-2B in high-aggressiveness BCa. Bars represent mean values ± SD. ^∗p < 0.05.

Figure 4

Correlation analysis between relative expression of survivin variants and adipokines in BCa. A random correlation analysis was performed to our set of studied genes. Each data point represents a sample where both genes were present in quantifiable levels. LEP and ADIPOQ show a strong positive correlation closely to a coefficient of 1. Similarly, S-2B and S-WT display a strong positive correlation. Furthermore, although some were moderate, we observed correlations such as the negative relationship of LEP with S-2B and S-WT and the negative relationship of ADIPOQ and these same two survivin variants. Lastly, we did not observe a correlation between the expression of adipokines and S-ΔEx3.