Metallothionein-like 5 expression in breast cancer tissue and its relationship with patient prognosis

Abstract

Objective To investigate the relationship of metallothionein-like 5(MTL5) expression in breast cancer tissue with the prognosis of breast cancer patients. Methods In our retrospective study, immunohistochemistry was performed on breast cancer tissue and corresponding paracancerous tissue samples of 77 patients who had no distant metastasis and neoadjuvant treatment before surgery and underwent the first surgery from January 2005 to September 2012, from the Chinese Human Genetic Resources Sharing Service Platform (No. 2005DKA2130). The patients were followed up for 3.3-11.0 years, until January 2016. Fisher’s exact test, χ2 test and non-parametric test were used to analyze the relationship between MTL5 expression in breast cancer tissues and clinicopathological characteristics of patients. Cox proportional hazard regression model was used to study the effect of MTL5 expression on recurrence and death risk of breast cancer patients.Kaplan-Meier method was used for survival analysis and the survival curves were plotted; log-rank test was used to compare the OS and recurrence-free survival between patients with high and low MTL5 expression. Results In the included 77 paired samples, 5 cases had detachment of the tissue sections from the slides, 29 cases had no MTL5 expression in cancer tissues and paracancerous tissues, and 2 cases had indiscernible difference in MTL5 expressions. So the aforementioned cases were excluded. In the remaining 41 cases, MTL5 expression in breast cancer tissues was significantly higher than that in paracancerous tissues in 21 cases, but lower in other 20 cases. MTL5 expression was correlated with age, axillary lymph node metastasis (P=0.021; Z=-2.281, P=0.023), but not correlated with ER, PR, tumor size, pathological type and HER-2 (χ2=0.034, P=0.853; χ2=0.042, P=0.837; χ2=1.177, P=0.278; P=0.663; P=1.000). Univariate analysis of the Cox proportional hazard regression model showed that axillary lymph node metastasis and MTL5 expression were risk factors for recurrence and death (recurrence: N3 stage vs N0 stage, HR=14.524, 90%CI: 2.322-90.858, P=0.004; high MTL5 expression vs low MTL5 expression, HR=8.752, 90%CI: 1.093-70.054, P=0.041; death: N3 stage vs N0 stage, HR=8.469, 90%CI: 1.495-47.988, P=0.016; high MTL5 expression vs low MTL5 expression, HR=8.255, 90%CI: 1.031-66.081, P=0.047). Multivariate analysis showed that breast cancer patients with high MTL5 expression had higher risk of recurrence compared with the patients with low MTL5 expression and MTL5 expression can be used as an independent risk factor of recurrence(HR=11.320, 95%CI: 1.022-125.436, P=0.048). Similarly, the patients with high MTL5 expression had higher risk of death compared with the patients with low MTL5 expression, so MTL5 expression can be used as an independent risk factor of death (HR=9.191, 95%CI: 1.037-81.430, P=0.046). The patients with high MTL5 expression had lower OS and recurrence-free survival compared with those with low MTL5 expression (χ2=5.652, 6.084; P=0.017, 0.014). Conclusion High MTL5 expression in breast cancer tissues may indicate a poor prognosis, so MTL5 can be used as a therapeutic target for breast cancer. Key words: Breast neoplasms; Survival analysis; Metallothionein-like 5