Overexpression of ANGPTL2 and LILRB2 as predictive and therapeutic biomarkers for metastasis and prognosis in colorectal cancer

Abstract

LILRB2 is an inhibitory receptor involved in immune cells. A variety of cancer cells have been observed to express LILRB2, which has been related to development of cancers. Recently, ANGPTL2 was found to be bound to LILRB2 as a high affinity ligand. Expression and function of LILRB2 and ANGPTL2 in colorectal cancer (CRC) remain unknown. To explore differential expression, 364 CRCs, 5 adenomas, and 205 normal samples for LILRB2 and 338 CRCs, 5 adenomas, and 232 normal samples for ANGPTL2 were studied in Oncomine and GEO databases. We noted that LILRB2 was significantly increased in CRC compared to adenoma and normal tissues. ANGPTL2 was higher in adenoma than normal tissues and further increased in CRC than adenoma. Copy number of LILRB2 and ANGPTL2 DNA was also more increased in CRC than in normal tissue. Furthermore, immunohistochemistry analysis of 155 pairs of primary CRC and normal tissues verified the positive rates of LILRB2 and ANGPTL2 were 87.10% (135/155) and 97.44% (151/155) in CRC, with almost no expression in normal tissues. LILRB2 and ANGPTL2 were significantly associated with tumor size, worse cell differentiation, lymph node metastasis, and advanced disease stage. Levels of ANGPTL2 were adversely related to survival of CRC patients, consistent with results in GEPIA (TCGA data) database. Moreover, a significant positive correlation was found between LILRB2 and ANGPTL2 in CRC. These findings suggest that ANGPTL2 and LILRB2 play an important role in CRC occurrence and progression. ANGPTL2 and LILRB2 could serve as novel biomarkers for treatment and prognosis of CRC.