Identification of candidate genes associated with triple negative breast cancer

Abstract

When triple negative breast cancer (TNBC) are analyzed by gene expression profiling different subclasses are identified, at least one characterized by genes related to immune signaling mechanisms supporting the role of these genes in the cancers. In an earlier study we observed differences in TNBC cell lines with respect to their expression of the cytokine IL32. Our analyses showed that certain cell lines expressed higher levels of the cytokine compared to others. Because TNBC are heterogeneous and immune-related genes appear to play a pivotal role in these cancers, we chose to examine the transcriptomes of the different cell lines based on IL32 expression. We performed group analyses of TNBC cell lines demonstrating high IL32 compared to low IL32 levels and identified IL32, GATA3, MYBL1, ETS1, PTX3 and TMEM158 as differentially associated with a subpopulation of TNBC. The six candidate genes were validated experimental and in different patient datasets. The genes distinguished a subset of TNBC from other TNBC, and TNBC from normal, luminal A, luminal B, and HER2 patient samples. The current project serves as a preliminary study in which we outline the discovery and validation of our list of six candidate genes.

PTX3 modulates the immunoflogosis in tumor microenvironment and is a prognostic factor for patients with clear cell renal cell carcinoma

“…Our observations are in line with previous evidences, which indicate that PTX3 could modulate the tumor microenvironment and could be a local or systemic marker of cancer-related inflammation. Increased PTX3 gene expression was reported in ovarian cancer with stromal signature [37], in aggressive breast cancer with distant bone metastases [38][39][40], in prostate cancer [41], in glioblastoma [42], in anaplastic thyroid carcinoma [43], and in soft tissue liposarcoma [44].…”

Circulating nuclear factor-kappa B mediates cancer-associated inflammation in human breast and colon cancer

“…PTX3, a modulator of inflammatory processes, is a member of the highly conserved pentraxin superfamily, which includes CRP, and it is associated with disease severity and mortality in patients with cancer (43,44). Up-regulation of PTX-3 gene expression has been described in aggressive breast cancer and distant bone metastases (44)(45)(46)(47). In CRC, serum PTX-3 levels were significantly increased compared to healthy individuals or patients with colorectal polyps, representing an independent prognostic factor for CRC patients (48).…”

The Long Pentraxin PTX3 as a Link Between Innate Immunity, Tissue Remodeling, and Cancer

“…Several lines of evidence indicate that PTX3 could be a local or systemic marker of cancer-related inflammation. Upregulation of PTX3 gene expression was observed associated to a stromal signature in ovarian cancer (116), and has been described in aggressive breast cancer and distant bone metastases (117–119), anaplastic thyroid carcinoma (120), soft tissue liposarcoma (121), prostate cancer (122), and glioblastoma (123). Increased circulating levels of PTX3 were observed in myeloproliferative neoplasms (124), soft tissue sarcomas (125), lung cancers (126–128), pancreatic carcinomas (129), gliomas (130), and hepatocellular carcinomas (131).…”