Diagnostic, prognostic and treatment response of perilipin1 gene in breast cancer

Abstract

BackgroundGenetic alterations in the perilipin (PLIN) family genes (PLIN1 to PLIN5) were infrequent in breast cancer (BC) where enhanced levels of PLIN1, PLIN3-5 were observed in the luminal A and luminal B subgroups, whereas increased PLIN2 expression was observed in the HER2-enriched and basal-like subgroups. However, the predictive value of PLIN1 for BC patient outcomes remains uncertain. In the present study, we aim to investigate the diagnostic, prognostic and treatment response roles of the PLIN1 gene expression in BC. MethodsWe obtained microarray BC trancriptomic data of 320 tumor (T) and 62 normal (N) breast samples from five GEO data-series; GSE7904 (38 T:7N), GSE42568 (101 T: 15 N), GSE26910 (6 T:6N), GSE45827 (144 T:7N), and GSE10810 (31 T:27 N). The Welch t test was used to analyze the significant differences in gene expression including PLIN1 with fold change > ±2 and p-value < 0.05. The expression of PLIN1 was confirmed by RTqPCR using clinical specimen samples from BC patients. The Kaplan-Meier Plotter was used to assess survival on large independent dataset (31 dataset for relapse-free survival and 14 datasets for overall survival) and significance was determined by calculating hazard ratios (>1) and log-rank p-values < 0.05. We also assessed the treatment outcomes of endocrine therapy (tamoxifen and aromatase-inhibitors), anti-HER2 therapy (trastuzumab and lapatinib), and chemotherapy (taxane, anthracycline, and ixabepilone) using robust statistical methods and correlated with PLIN1 gene expression. ResultsWe identified significantly reduced expression of PLIN1 (FC = −30.76, p value = 2.183e−24) in BC samples compared with normal controls. Our qPCR result confirmed the microarray expression pattern of PLIN1 in BC. Survival analysis revealed PLIN1 to be a moderately important prognostic biomarker. Our findings highlight the effectiveness of trastuzumab and anthracycline in classifying treatment responses, supported by Mann-Whitney tests indicating statistical significance in gene expression differences between responders and non-responders. ConclusionIn conclusion, our findings indicate that PLIN1 is one of the most down-regulated genes and a moderately important biomarker in BC for prognostic purposes. PLIN1 was a good indicator of trastuzumab and anthracycline treatment responses in BC.