Association Between Histone Methyltransferase hSETD1A and Prognosis in Patients With Triple-Negative Breast Cancer After Surgery

Abstract

Breast cancer, the most common cancer in women, is a serious public health issue. Triple-negative breast cancer (TNBC), which lacks expression of the estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2, accounts for ∼15% of breast cancer cases. Treatment of TNBC patients has proven difficult because of the lack of expression of hormone receptors. We conducted a retrospective study to investigate the prognostic impact of histone methyltransferase, hSETD1A, on overall survival in TNBC cases after surgery. In total, 159 TNBC cases were enrolled and clinicopathological characteristics were obtained from medical records. hSETD1A status of each subject was determined using immunohistochemistry. The chi-squared test was used to compare 5-year overall survival rates of all subjects according to clinical characteristics, and both univariate and multivariate analyses were conducted to calculate the hazard ratios and 95% confidence intervals. Advanced tumor-node-metastasis stage stage, larger tumor size, vascular invasion, metastasis in the initial diagnosis, and hSETD1A expression were correlated with worse outcome. Among all factors identified, metastasis in the initial diagnosis had the greatest impact on survival. The results indicated that hSETD1A positivity was correlated with shorter survival among TNBC cases, suggesting it may serve as a prognostic biomarker for patients with TNBC.

Identification of a novel target of SETD1A histone methyltransferase and the clinical significance in pancreatic cancer

“…Here we revealed that SETD1A was detected highly expressed in more than half (51.4%) of PDAC cases by immunohistochemistry, with the positive ratio of SETD1A similar to that in colorectal (67.8%), lung (48.9%) and breast (50.9%) cancer in the previous reports using immunohistochemistry 20,27 . As shown in Figure 1 and Table S1, SETD1A overexpression was correlated with venous invasion and worse prognosis with PDAC.…”

“…Here we revealed that SETD1A was detected highly expressed in more than half (51.4%) of PDAC cases by immunohistochemistry, with the positive ratio of SETD1A similar to that in colorectal (67.8%), lung (48.9%) and breast (50.9%) cancer in the previous reports using immunohistochemistry. 20 , 27 As shown in Figure 1 and Table S1 , SETD1A overexpression was correlated with venous invasion and worse prognosis with PDAC. A clinical association between SETD1A overexpression and poor survival has also been reported in cancers, 17 , 18 , 20 and higher SETD1A levels are associated with a more advanced clinical stage, vascular invasion, and metastasis in triple‐negative breast cancer.…”

Clinicopathologic significance of protein lysine methyltransferases in cancer

“…This association persisted after multivariate analyses for known independent predictors of survival in breast cancer, such as TNM stage and histologic grade were performed. Additionally, higher SETD1A levels were associated with more advanced clinical stage, vascular invasion and metastasis [41]. These findings underpin the role of SETD1A in breast cancer pathogenesis and its potential therapeutic impact in this disease.…”

“…Zhu et al detected SETD1A immunopositivity in 50.9% of 159 TNBCs with 5-year overall survival rates at 3.5% in relation to 39.6% in SETD1A-negative tumors [41]. This association persisted after multivariate analyses for known independent predictors of survival in breast cancer, such as TNM stage and histologic grade were performed.…”

The Epigenetics of Triple-Negative and Basal-Like Breast Cancer: Current Knowledge

“…Other histone-modifying enzymes that can promote aggressiveness of TNBC are histone methyltransferases. A histone methyltransferase, hSETD1A, has been associated with poor outcome and decreased overall survival rates in a retrospective study on 159 TNBC patients [ 90 ], indicating that it could be further investigated as a prognostic marker.…”