Expression Of Polo-like Kinase 4(PLK4) In Breast Cancer And Its Response To Taxane-resistant

Background PLK4, a member of polo-like kinase family(PLKs), plays an important role in the process of the centrosome duplication. Overexpression of PLK4 always results in centrosome proliferation and chromosome instability. Chromosome instability is an characteristic of tumor cells, and play an important role in tumor invasion. In light of the features, several studies have demonstrated the association between the expression of PLK4 and human tumor. But the studies mainly focus on colon cancer, gastric cancer, and liver cancer, no report has demonstrated the role of PLK4 m RNA and PLK4 in breast cancer. In addition, PLK4 works as gamma tubulin upstream regulatory factors, and their directly interaction affects the structure and function of microtubules. Taxane mainly acts on microtubules, so we speculate that PLK4 may associate with the sensitive of neoadjuvant chemotherapy.Objective Polo-like kinase 4(PLK4) is an important evolutionarily regulator involved in centrosome duplication. We here investigated the expression of PLK4 m RNA and PLK4 in breast cancer, and analyzed the association between the level of PLK4 and the clinical pathological features and prognosis of breast cancer. In addition, we also evaluated its predictive value for response to taxane-based neoadjuvant chemotherapy.Methods Firstly, the PLK4 m RNA expression was measured in breast cancer tissues and corresponding normal breast tissues from 30 breast cancer patients by quantitative real-time polymerase chain reaction(PCR). We analyzed the association between the level of PLK4 and the clinical pathological features(age, tumor size, histological grade, lymph node status, ER, PR HER2, and so on) of breast cancer. The association of the expression of PLK4 with clinicopathological parameters(age, tumor size, histological grade, lymph node status, ER, PR HER2, and so on) and prognostic significance was evaluated in 154 cases of invasive breast cancer by immuohistochemistry. In addition, we examined the changes of PLK4 expression in biopsy and postoperative tumor specimens of another 64 breast cancer patients who received taxane-based neoadjuvant chemotherapy by immuohistochemistry.Results1. In the study, 26 patients(86.7%) showed PLK4 m RNA amplification(T/N>1), while only 2 cases appeared no change(T/N?1), and 2 cases had a decreased expression. Compared to the level of PLK4 m RNA in normal tissue, the expression of PLK4 in breast cancer tissue has a statistically significant difference(P=0.021).2. The expression of PLK4 mRNA has no correlation with age, histological grade, tumor size, lymph node status, ER status, PR status, and HER2 status(all P>0.05).3. PLK4 protein expressed in the cytoplasm, and PLK4 was expressed in 150(150/154, 97.4%) cases(+ group 72 cases, ++ group 62 cases, +++ group 17 cases), and was only no expression in 4(4/154, 2.6%) cases.4. The expression of PLK4 had no correlation with age, tumor size, histogical grade, ER status, PR status, HER2 status, molecular phenotype, and chemotherapy(P>0.05). There is a positive correlation of PLK4 expression with higher incidence of lymph node metastasis and distant metastasis or surrounding recurrence(P=0.043; P=0.006).5. According to the Kaplan-Meier analysis results, the high expression of PLK4 had a poor PFS and OS than the low expression of PLK4(P=0.003; P=0.003). High PLK4 expression was an adverse prognostic factor of PFS and OS. According to multiple factors analysis, PLK4 is an independent prognostic factors for PFS(P=0.007), but not for OS(P=0.088).6. The level of PLK4 expression negatively correlated with taxane-based neoadjuvant chemotherapy sensitivity(rs=-0.253, P=0.044).7. PLK4 expression was found have a significant change overall at post-neoadjuvant chemotherapy(P=0.003). There were no significant changes of PLK4 expression between the biopsy and tumor specimens of breast cancer patients who had no response to taxane-based neoadjuvant chemotherapy(P=0.611), while there was a significant decrease in the patients with partial response or good response(P=0.031,P=0.008). There was low expression of PLK4 in 33 cases at pre-neoadjuvant chemotherapy, and only one case had a high expression after neoadjuvant chemotherapy.Conclusion PLK4 m RNA amplification is common in breast cancer, but its expression has no correlation with the clinical pathological features. There is a positive correlation of PLK4 expression with higher incidence of lymph node metastasis and distant metastasis or surrounding recurrence. PLK4 high expression is an independent prognostic factors for breast cancer patients with poor prognosis. PLK4 expression negatively correlated with taxane-based neoadjuvant chemotherapy sensitivity. Take together, PLK4 can be used as a ptedictor of prognosis of breast cancer, also can be used as a predictor of neoadjuvant chemotherapy sensitivity.