Perturbation of specific transcripts in peripheral blood mononuclear cells in breast cancer: a case control pilot study

Introduction: Breast cancer (BC) is the most common type of diagnosed cancer worldwide and the leading cause of cancer death in women and it is the second most frequent cancer-causing mortality for women worldwide. Peripheral blood-based biopsy for BC could be a promising tool for risk prediction and diagnosis. In this study, we aimed to evaluate the gene expression profile of PBMCs in Italian patients with BC. Methods: In this case-control pilot study, we isolated PBMCs from 22 BC patients and 21 healthy controls and evaluated the expression of a panel of 52 target genes related to BC or circadian rhythm by a customized TaqMan Open Array Real-Time PCR panel. Results: Among the differentially expressed genes, 22 remained unchanged. These unchanged genes are mainly involved in cellular processes, including the circadian clock, cellular responses to stress/stimuli, the immune system, signal transduction, and metabolism. We found a total of 30 significantly de-regulated genes. In particular, 8 genes, including PARP6, IGFR1, EZH2, VEGFA, NOTCH1, CD44, BCAR1, and CD24A, resulted significantly down-regulated in patients with BC compared to Controls, while 22 genes were significantly up-regulated in BCs patients compared to Controls. We found several already reported BC-associated genes up-regulated in PBMCs of our BC patients, but FOXO3, ARNTL, and ADAM17 emerged as the most strongly up-regulated. The enrichment pathways analysis highlight that de-regulated genes are mainly involved in the regulation of gene expression and transcription, signal transduction, and immune system response. Discussion: The results of our pilot study demonstrated that the evaluation of PBMC gene signature could be a valuable tool for primary prevention and early diagnosis of BC in several high-risk settings, thus reducing the global mortality associated with this tumour. Take-home message: Non-invasive screening programs, particularly those adopted in workplaces, may have a great impact on early diagnosis and good prognosis for BC. Our study provided proof of concept that the development of a screening test based on PBMC-derived gene expression biomarkers could be a viable route.