Distinct microbiological signatures associated with triple negative breast cancer

Abstract

Infectious agents are the third highest human cancer risk factor and may have a greater role in the origin and/or progression of cancers, and related pathogenesis. Thus, knowing the specific viruses and microbial agents associated with a cancer type may provide insights into cause, diagnosis and treatment. We utilized a pan-pathogen array technology to identify the microbial signatures associated with triple negative breast cancer (TNBC). This technology detects low copy number and fragmented genomes extracted from formalin-fixed paraffin embedded archival tissues. The results, validated by PCR and sequencing, define a microbial signature present in TNBC tissue which was underrepresented in normal tissue. Hierarchical clustering analysis displayed two broad microbial signatures, one prevalent in bacteria and parasites and one prevalent in viruses. These signatures demonstrate a new paradigm in our understanding of the link between microorganisms and cancer, as causative or commensal in the tumor microenvironment and provide new diagnostic potential.

DGCA: A comprehensive R package for Differential Gene Correlation Analysis

“…Further, genes in ER+ specific gene pairs were enriched in calcium ion binding (OR = 1.5, FDR = 0.008), which is consistent with the ability of calcium to stimulate estrogen receptor-alpha expression and mimic estrogen [69, 70]. On the other hand, genes in gene pairs with a gain of correlation in TN samples were enriched in the GO term negative regulation of viral life cycle (TN OR = 4.9, FDR = 0.006), which may be explained by reports that a subset of TN breast cancers are associated with viral infection [71]. Surprisingly, despite the presence of multiple gene sets related to estrogen-regulated genes in the GO annotation set employed, including “estrogen receptor activity” and “estrogen receptor binding”, none of these were identified as significantly enriched in differentially correlated gene pairs unique to ER+ or TN samples.…”

Liquid Biopsy in the Diagnosis of HPV DNA in Breast Lesions

“…The presence of HPV DNA in NDs confirms that breast tissues harbor mucosal high-risk HPV as constituents of the local virome. These data are in agreement with recent literature also showing that cutaneous HPVs take part in it [2]. As HPV DNA is more represented in IP, its presence seems not to be strictly related to malignancy.…”

“…The presence of HPV DNA in breast cancer has been widely investigated in the last three decades [1], but few data are available on its presence in benign breast lesions, in other words, intraductal papilloma (IP). A plethora of pathogens has been found in triple negative breast cancer, the most aggressive breast cancer phenotype, including mucosal and cutaneous HPVs [2]. The presence of HPV DNA has been reported in biological fluids such as milk and colostrum of lactating women as well as in ductal lavages from women at increased risk of breast cancer [3,4].…”

The ovarian cancer oncobiome

“…Many studies have found that DNA of the Human Papillomavirus (HPV)-16 and HPV-18 is associated with ovarian carcinomas [2–5]. However, recent studies from our laboratory and others [6–8] have found that the tumor microbiome may be far more complex. We have defined unique microbial signatures associated with triple negative breast cancer and head and neck cancer [6] (Banerjee et al ., unpublished).…”