CRC (Colorectal Cancer) is considered as one of the most significant cancers worldwide, with 1.01 million new cases and more than 550000 deaths per year . Despite the significant advances in the diagnosis and treatment of CRC, the survival rate decreases for patients diagnosed with metastatic and regional disease . The reported overall median survival time of CRC is only 1.1 years ; therefore, understanding the mechanism of colorectal cancer will be promising for the treatment and prevention of colorectal cancer.
The lack of predictive and prognostic biomarkers with the ability to predict therapy response and recurrence of the disease is an important issue that needs to be addressed. The LRIG1 (the leucine-rich repeats and immunoglobulin-like domains 1) as an emerging tumor suppressor and its paralogs LRIG2 (the leucine-rich repeats and immunoglobulin-like domains 2) and LRIG3 (the leucine-rich repeats and immunoglobulin-like domains 3), are considered to have the prognostic significance in diverse kinds of cancers, such as head-and-neck [4, 5], prostate , breast [7, 8], uterine cervical cancer [9–11], and cutaneous squamous cell carcinoma , and glioma [13, 14].
The locus of LRIG1 is located on chromosome 3p14.3. The encoding protein is a transmembrane protein consists of an extracellular domain including three immunoglobulin (Ig)-like domains and fifteen leucine-rich repeats. The leucine-rich repeats and immunoglobulin-like domains have interactions with all four extracellular region binding protein B receptor family members leads to regulation of receptor levels by subsequent lysosomal degradation and increasing ubiquitination, independent of ligands [15–17]. Also the LRIG1 considered as a marker of human epithelial stem cells in a quiescent non-proliferative state . The enhanced proliferation associated with epithelial hyper-proliferation in vivo and stem cell expansion in vitro is the result of the genetic erosion of the leucine-rich repeats and immunoglobulin-like domains [18, 19]. It is recommended by the lineage tracing that the leucine-rich repeats and immunoglobulin-like domains marks non-cycling, long-lived stem cells of the 4 quiescent intestinal stem cell niche in the crypt ; and also progenitor cells in the stomach that are involved in restoring gastric cell mucosa after DMP-777 induced acute damage .
Although the LRIG1 role in cancers are well established, little is known about its association with clinico-patho-physiology characteristics of CRC patients. Here the LRIG1 expression in the lesions of CRC patients were studied in order to evaluate its relationship with the major clinic-histological prognostic factors and its respective impacts on patient prognosis hopping to achieve the approaches for colorectal cancer management. Therefore, the main goal of the present study was to compare and analyze the expression levels of the LRIG1 gene in samples of tumor and normal colorectal tissues of CRC patients by quantitative real-time RT-PCR and immunohistochemical (IHC) techniques. Moreover, to estimate the prognostic indicator of the mentioned gene expression levels, we surveyed their correlations with clinicopathological parameters, as well as the overall survival (OS) of patients with CRC.