Discoidin Domain Receptor 2 Expression as Worse Prognostic Marker in Invasive Breast Cancer.

Irene Romayor,Aitor Benedicto,Joana Márquez,Marina Luque García-Vaquero,Ramón Barceló,Beatriz Arteta,Pranshu Sahgal

doi:10.1155/2022/5169405

Abstract

Discoidin domain receptor 2 (DDR2) is arising as a promising therapeutic target in breast carcinoma (BC). The ability of DDR2 to bind to collagen promotes protumoral responses in cancer cells that influence the tumor microenvironment (TME). Nonetheless, the interrelation between DDR2 expression and TME modulation during BC progression remains poorly known. For this reason, we aim to evaluate the correlation between intratumoral expression of DDR2 and the infiltration of the main TME cell populations, cancer-associated fibroblasts (CAFs), and tumor-associated macrophages (TAMs). First, collagen and DDR2 expression levels were analyzed in human invasive BC samples. Then, DDR2 status correlation with tumor aggressiveness and patient survival were retrieved from different databases. Subsequently, the main pathways, cell types, and tissues correlated with DDR2 expression in BC were obtained through bioinformatics approach. Finally, we studied the association of DDR2 expression with the recruitment of CAFs and TAMs. Our findings showed that, together with the expected overexpression of TME markers, DDR2 was upregulated in tumor samples. Besides, we uncovered that altered TME markers were linked to DDR2 expression in invasive BC patients. Consequently, DDR2 modulates the stromal reaction through CAFs and TAMs infiltration and could be used as a potential worse prognostic factor in the treatment response of invasive BC.

Highlights

Breast carcinoma (BC) is the most prevalent malignancy in women and the leading cause of death among female population [1, 2]
Apart from its histology, BC tumor is classified according to its molecular phenotype regarding the presence of three different biomarkers: estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). us, luminal-like BC is characterized by ER/PR positive and HER2 negative, HER2-enriched is defined by ER/PR negative or positive and HER2 positive, and triple-negative tumor is described by the absence of these markers [5]
Discussion e extracellular matrix (ECM) is one of the main components of the tumor microenvironment (TME). e importance of these extracellular elements resides in their ability to promote significant changes in the behavior of cancer cells through receptor-mediated ECM-tumor cell interactions. ese alterations exert a positive effect on cancer cells, by means of chemoresistance, as well as increased proliferation and migration, among others [40]

Summary

Introduction

Breast carcinoma (BC) is the most prevalent malignancy in women and the leading cause of death among female population [1, 2]. Invasive lobular carcinoma (ILC) represents the second most common subclass of BC, with an incidence of around 15% [3]. Both subtypes differ in clinical, pathological, and biological aspects, with the expression of E-cadherin being the main hallmark of IDC [4]. Us, luminal-like BC is characterized by ER/PR positive and HER2 negative, HER2-enriched is defined by ER/PR negative or positive and HER2 positive, and triple-negative tumor is described by the absence of these markers [5]. Current adjuvant treatments are based on targeting these proteins before or after surgery [6, 7], excepting triple-negative BC, for which chemotherapy in combination with immunotherapy regimens are commonly used [8]. Despite medical advances, more than 20% of women with early-stage BC will suffer metastatic disease [9], which reflects the need for new targeted therapies

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