Polymorphisms in CLDN1 are associated with age and differentiation of triple-negative breast cancer patients

Hu, Aimin; Li, Junyu; Ruan, Shufang; Fan, Ying; Liao, Yuqian

Breast cancer is one of the most common cancers in women around the world [1] . It is a highly heterogeneous disease which for decades has been divided into several subgroups according to immunohistochemical staining (IHC) of three receptors: estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) [2] . Triple-negative breast cancer (TNBC) is defined as lacking expression of ER, PR, and HER2. It accounts for 15-20% of all breast cancers and is characterized by enhanced invasiveness and metastatic capacity, young age of onset and poor prognosis [3] . However, even within TNBC patients, distinct response to treatments and prognosis was observed [4] . With the development of molecular profile, four to six distinct subtypes have been defined within TNBC, such as basal-like and claudin-low [5] . Investigators are making more efforts to explore novel biomarkers to clarify the characteristics of TNBC [6] . Claudins (CLDNs) are key cell adhesion molecules, which compose tight junctions (TJs), regulate paracellular permeability, and maintain cell polarity [7] . There are 27 members in CLDNs family, each member is predicted to possess four transmembrane domains with intracellular amino and carboxyl-termini in the cytoplasm and two extracellular loops [8] . It has been reported that CLDN1 expression levels were decreased in breast cancer [9] , colorectal carcinoma [10] , glioblastoma [11] , and melanoma brain metastasis [12] . In contrast, only a few literatures reported about polymorphisms in CLDN genes and their role in cancer development [13, 14] . Our study was designed to explore the relationship between genetic variants in CLDN1 and clinicopathological characteristics or survival of TNBC.