Leukocyte immunoglobulin-like receptor B2 overexpression as a promising therapeutic target and noninvasive screening biomarker for colorectal cancer

Abstract

Background: Colorectal cancer (CRC) has become the second most deadly malignancy in the world, and the exploration of screening markers and precise therapeutic targets is urgent. Our previous research identified leukocyte immunoglobulin-like receptor B2 (LILRB2) protein as a characteristic protein of CRC, but the association between LILRB2 expression and clinicopathological features, the internal mechanism related to CRC progression, and screening diagnostic efficacy are not clear. Therefore, we hypothesized that LILRB2 is significantly highly expressed in CRC tissues, correlated with advanced stage and a poor prognosis, and could be used as a therapeutic target and potential screening biomarker for CRC.

Aim: To explore whether LILRB2 can be used as a potential therapeutic target and noninvasive screening biomarker for CRC.

Methods: Patients who underwent radical surgery for CRC at China-Japan Friendship Hospital between February 2021 and October 2022 were included. Cancer and paracancerous tissues were collected to verify LILRB2 expression, and the association between LILRB2 expression and clinicopathological features was analysed. Serum was collected from CRC patients, adenoma patients and healthy controls during the same period to assess the diagnostic value of LILRB2 as a noninvasive screening biomarker, and its diagnostic value was further compared with that of the traditional markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9).

Results: A total of 58 CRC patients were included, and LILRB2 protein was significantly overexpressed in cancer tissues compared with paracancerous tissues (P < 0.001). Angiopoietin-like protein 2 (ANGPTL2) protein, as the ligand of LILRB2, was synergistically overexpressed in CRC tissues (P < 0.001), and overexpression of LILRB2 and ANGPTL2 protein was significantly correlated with poor to moderate differentiation, vascular involvement, lymph node metastasis, distant metastasis, advanced tumor-node-metastasis stage and a poor prognosis (P < 0.05), which suggested that LILRB2 and ANGPTL2 are closely associated with CRC progression. In addition, serum LILRB2 concentrations increased stepwise in healthy individuals, adenoma patients and CRC patients with statistically significant differences. The sensitivity of serum LILRB2 for the diagnosis of CRC was 89.74%, the specificity was 88.89%, the area under the curve was 0.95, and the diagnostic efficacy was better than that of conventional CEA and CA19-9.

Conclusion: LILRB2 protein can be used as a potential novel therapeutic target and noninvasive screening biomarker for CRC, which is beneficial for early screening and precise treatment.

Keywords: Angiopoietin-like protein 2; Colorectal cancer; Leukocyte immunoglobulin-like receptor B2; Noninvasive screening biomarker; Therapeutic target.