Expression and significance of Shh, Gli1 and β-catenin in triple-negative breast cancer tissues

Abstract

Objective: To detect the expression of Shh, Gli1 and β-catenin in triple negative breast cancer tissues and paracancer breast tissues by qRT-PCR and immunohistochemistry and to analyze their correlation with clinicopathological features.

Methods: (1) qRT-PCR was used to detect the mRNA expression of Shh, Gli1 and β-catenin in 30 cases of triple negative breast cancer and their paracancer breast tissues, and the correlation among them was analyzed. (2) The expression of Shh, Gli1 and β-catenin proteins in 30 triple negative breast cancer and their paracancer breast tissues was detected by immunohistochemistry, and their correlation with clinicopathological features was analyzed.

Results: (1) Shh mRNA expression (1.2334 ± 0.27867), Gli1 mRNA expression (1.2135 ± 0.20636) and β-catenin mRNA expression (1.1421 ± 0.32330) in triple negative breast cancer tissues were higher than that in paracancer breast tissues, i.e., Shh mRNA expression (1.0022 ± 0.06721), Gli1 mRNA expression (1.0003 ± 0.02420) and -catenin mRNA expression (1.0033 ± 0.07920) were significantly different (p < .05). There was a significantly positive correlation between the mRNA expression of Shh and Gli1 (r = .989, p < .001), and between the mRNA expression of Shh and β-catenin (r = .868, p < .001). There was a significantly positive correlation between the mRNA expression of Gli1 and β-catenin expression (r = .869, p < .001). (2) The positive expression rates of Shh, Gli1 and β-catenin in triple negative breast cancer tissues were 93.3% (28/30), 96.7% (29/30) and 93.3% (28/30), respectively, which were higher than those in paracancer tissues 60% (18/30), 73.3% (22/30) and 73.3% (22/30), the differences were statistically significant (p < .05). There was a significantly positive correlation between the mRNA expression of Shh and Gli1 (r = .958, p < .001), and between the mRNA expression of Shh and β-catenin (r = .952, p < .001). There was a significantly positive correlation between the mRNA expression of Gli1 and β-catenin expression (r = .927, p < .001). The expression of Shh, Gli1 and β-catenin protein in triple negative breast cancer was not correlated with age and tumor size (p > .05), but Shh was positively correlated with histological grade (G) (r = .774, p < .001). Furthermore, Gli1 was positively correlated with histological grade (r = .757, p < .001). β-catenin was positively correlated with histological grade (r = .739, p < .001). Shh was positively correlated with TNM staging (r = .460, p = .010). Gli1 was positively correlated with TNM staging (r = .414, p = .023). -catenin was positively correlated with TNM staging (r = .404, p = .027). Shh was positively correlated with lymph node metastasis (r = .540, p = .002). Gli1 was positively correlated with lymph node metastasis (r = .515, p = .004). β-catenin was positively correlated with lymph node metastasis (r = .559, p = .001).

Conclusions: (1) The up-regulated expression of Shh, Gli1 and β-catenin proteins in triple negative breast cancer suggests that Shh, Gli1 and β-catenin proteins are involved in tumor genesis. The combined detection of the three proteins may provide a theoretical basis for the diagnosis and prognosis evaluation of triple negative breast cancer. (2) Shh was positively correlated with Gli1 protein expression and β-catenin protein expression. Gli1 was positively correlated with β-catenin protein expression, suggesting that the three types of proteins play a synergistic role in the occurrence and development of TNBC. There may be crosstalk in the Wnt/β-catenin and Hedgehog signaling pathways in TNBC, which may provide a new approach for the treatment of TNBC. (3) The expression of Shh, Gli1 and β-catenin proteins was correlated with the degree of differentiation, TNM staging and lymph node metastasis of triple negative breast cancer, but not correlated with age and tumor size. Therefore, it was predicted that the three types of proteins were related to the invasion, metastasis and prognosis of TNBC.