Altered Sirtuin 7 Expression is Associated with Early Stage Breast Cancer

Abstract

Background: To evaluate sirtuin-7 (SirT7) mRNA expression status in breast cancer patients with different metastatic stages and survey SirT7 mRNA expression status in eight different types of cancer.

Methods: The expression of SirT7 in the commercially available TissueScan qPCR Breast Cancer Disease cDNA arrays containing 16 normal, 23 Stage I, 36 IIA, 22 IIB, 8 IIIA, 23 IIIA, 6 IIIB, 13 IIIC, and 5 IV were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Similar analysis was performed in TissueScan qPCR Cancer Survey cDNA array, which includes breast, colon, kidney, liver, lung, ovarian, prostate, and thyroid specimens.

Results: The mRNA expression levels of SirT7 were significantly higher in breast cancer samples compared to normal breast specimens (P < 0.001). Stratification of patients into groups according to metastatic stages indicated statistically significantly higher levels of SirT7 mRNA in CS-I, CS-II, and CS-III when compared to normal breast tissue (P < 0.05). Notably, SirT7 mRNA levels were higher in CS-I, CS-IIA, CS-IIB, and CS-IIIA (P < 0.05). Additionally, there were significantly lower SirT7 mRNA levels in thyroid carcinoma when compared to their corresponding normal tissue (P < 0.05).

Conclusions: Our results indicate an increase in the mRNA expression level of SirT7 in breast cancer, particularly in CS-I, CS-IIA, CS-IIB, and CS-IIIA. The relationship of altered SirT7 with breast cancer progression and patient survival should be prospectively explored in future studies.

Keywords: breast cancer; cDNA arrays; metastasis; sirtuin-7.

Figure 1

mRNA expression levels of SirT7 in normal and breast cancer specimens from Breast Cancer cDNA arrays (BCRT101, BCRT102 and BCRT104). The expression levels of SirT7 normalized to the expression levels of β-actin. Black bars represent the median log₂ fold change value of SirT7. Asterisks indicate statistically significant differences (Mann-Whitney Rank Sum Test; **P < 0.001; n = 16-normal, 128-breast adenocarcinoma specimens).

Figure 2

Relative mRNA expression levels of SirT7 in Breast Cancer cDNA arrays (BCRT101, BCRT102 and BCRT104) following stratification of patients into groups according to metastatic stage. The expression levels of SirT7 normalized to β-actin as a house keeping gene. Average normal ΔCt values were used for calculation of fold change differentials for each sample. Black bars represent the median log₂ fold change value of SirT7; n = 16-normal, 23-Stage I, 58-II, 42-III, 5-IV. Asterisks indicate statistically significant differences (One Way ANOVA on Ranks; *P < 0.05).

Figure 3

TaqMan qRT-PCR measurements of relative mRNA expression levels for SirT7 run on Breast Cancer cDNA arrays (BCRT101, BCRT102 and BCRT104) containing normal and cancer specimens with different metastatic stages. For each sample, the expression levels of SirT7 normalized to housekeeping gene (β-actin). Average normal ΔCt values were used for calculation of fold change differentials for each sample. Black bars represent the median log₂ fold change value of SirT7. Asterisks indicate statistically significant differences (One Way ANOVA on Ranks; *P < 0.05).

Figure 4

TaqMan qRT-PCR measurements of relative mRNA expression levels of SirT7 run on Cancer Survey cDNA arrays (CSRT101) containing 8 different types of cancers with their corresponding normal tissues (breast, colon, kidney, liver, ovary, thyroid, lung and prostate). The expression levels of SirT7 normalized to expression levels of β-actin housekeeping gene. Average normal ΔCt values were used for calculation of fold change differentials for each sample. Black bars represent the median log₂ fold change value of SirT7. Asterisks indicate statistically significant differences (Mann-Whitney Rank Sum Test; *P < 0.05).