MASTL is a potential poor prognostic indicator in ER+ breast cancer.

OBJECTIVE: In this study, we aimed to explore prognostic value of MASTL (microtubule-associated serine/threonine kinase-like) in breast cancer patients on the basis of ER status and molecular subtypes. MATERIALS AND METHODS: The raw microarray data (GDS5666) of 4T1 derived bone-aggressive explant and primary tumor explant were reanalyzed to identify the dysregulated genes. To pool previous annotated genomic data that assessed the association between MASTL expression and metastatic relapse (MR) risk, MR-free survival, any event (AE, defined as any relapse or death) risk, and AE-free survival in breast cancer patients, a meta-analysis was performed by bc-GenExMiner 4.0. RESULTS: MASTL is a significantly upregulated gene in 4T1 bone-aggressive explant compared to primary tumor explant. Univariate Cox analysis showed that high MASTL expression is associated with a higher risk of MR (HR: 1.43, 95%CI: 1.28-1.60; p<0.001) and a higher risk of AE (HR: 1.27, 95%CI: 1.18-1.37; p<0.001) in ER+ breast cancer. Also, high MASTL expression also predicts a worse MR-free survival (HR: 1.74, 95%CI: 1.40-2.17; p<0.001) and a worse AE-free survival (HR: 1.42, 95%CI: 1.23-1.63; p<0.001) in ER+ breast cancer. However, the associations were not observed in ER- patients. The following NPI adjusted analyses confirmed the results of univariate Cox analysis. In Single Sample Predictors (SSPs) and Subtype Clustering Models (SCMs) subtypes, high MASTL expression is associated with increased risk of AE and predicts a poor AE-free survival in ER+ subgroups. CONCLUSIONS: MASTL might be a valuable indicator of MR risk and AE risk in ER+ patients, but not in ER- patients.

Bioinformatic analysis of prognostic value of ARAP3 in breast cancer and the associated signaling pathways.

OBJECTIVE: In this study, we tried to pool previous annotated genomic data to assess the association between ARAP3 expression and metastatic relapse (MR) risk in patients with breast cancer. Moreover, we also investigated the signaling pathways in which ARAP3 might be involved in breast cancer. MATERIALS AND METHODS: The raw microarray data (GDS5666) that compared gene transcriptional profiles of 4T1 derived lung-aggressive explant and primary tumor explant were reanalyzed to identify the dysregulated genes. ARAP3 mRNA expression, its association with MR-free survival and its co-upregulated genes in breast cancer, were studied by data mining in TCGA database and Breast Cancer Gene-Expression Miner Version 4.0 (bc-GenExMiner 4.0). RESULTS: ARAP3 is a significantly upregulated gene in the metastatic breast tumor cells. The ER- patients with high ARAP3 expression had significantly increased the risk of MR, regardless of the nodal status. Patients in ER-/Nm group with high ARAP3 expression had the highest risk of MR (HR: 1.25; 95%CI: 1.10-1.41, p<0.001). In patients with basal-like tumors, High ARAP3 level is associated with significantly worse MR-free survival (HR: 1.63, 95%CI: 1.22-2.19, p=0.001). ARAP3 might be closely related to the NOTCH4 and CDH5 signaling pathways in breast cancer. CONCLUSIONS: The expression level of ARAP3 might be a useful indicator of the metastatic likelihood of the basal-like breast tumors. ARAP3 might be involved in NOTCH4 and CDH5 related signaling pathways, but the underlying mechanism should be further studied.

Higher RABEX-5 mRNA predicts unfavourable survival in patients with colorectal cancer.

OBJECTIVE: The aim of the present study was to clarify the expression pattern and prognostic role of RABEX-5 mRNA in colorectal cancer (CRC) patients. PATIENTS AND METHODS: RABEX-5 mRNA levels in 187 CRC were examined by Real-time polymerase chain reaction. Then, the association of RABEX-5 mRNA levels with clinicopathological features was analyzed. Survival curves were plotted using the Kaplan-Meier method and differences in survival rates were analyzed using the log-rank test. The influence of each variable on survival was examined by the Cox multivariate regression analysis. RESULTS: RABEX-5 mRNA expression was significantly upregulated in CRC tissues compared with the adjacent noncancerous tissues (p < 0.01). By statistical analyses, high RABEX-5 mRNA expression was observed to be closely correlated with histology/differentiation (p = 0.010), N classification (p = 0.004), and TNM stage (p = 0.004). Kaplan-Meier curves showed that patients with high RABEX-5 mRNA expression showed unfavorable overall survival (OS) than the low RABEX-5 mRNA expression group (p < 0.001). Finally, univariate and multivariate analyses showed that RABEX-5 mRNA expression was an independent predictor of overall survival (p < 0.05). CONCLUSIONS: RABEX-5 mRNA may be a promising biomarker for the detection and prognosis evaluation of CRC.