ITGB4 as a novel serum diagnosis biomarker and potential therapeutic target for colorectal cancer

Abstract

Abstract Purpose To develop new and effective biomarkers for the diagnosis of colorectal cancer (CRC). Experimental design The serum expression of ITGB4 (49 CRC and 367 HC) was detected by enzyme‐linked immunosorbent assay (ELISA), and its diagnostic value was analyzed using the receiver operating characteristic (ROC) curve. The sensitivity and specificity of ITGB4 in CRC diagnosis were calculated through statistical analysis. The optimal clinical cutoff value was calculated using the Youden index, and diagnostic efficacy was analyzed in a larger serum sample (98 CRC and 1631 non‐CRC). The expression of ITGB4 was measured by CyTOF (cell experimental technology) at the single‐cell level, and characteristics were analyzed using viSNE and SPADE TREE. Results Serum ITGB4 and CEA levels were significantly higher in CRC patients than in HC and non‐CRC patients. The use of serum ITGB4 levels for the diagnosis of CRC has a high sensitivity (79%) but not high specificity when the clinical cutoff value was 0.70 ng/mL. However, the optimal cutoff value was 1.6 ng/mL with 86.2% specificity and 52.0% sensitivity, and the diagnostic efficacy was greatly improved with high specificity (82.0%) and sensitivity (71.4%) when combined with CEA. ITGB4 expression characteristics were measured and related to the expression of EpCAM, Ck8/18, and perforin at the single‐cell level. Single‐cell analysis showed that cell clusters with low expression of CK8/18 and ITGB4 were more sensitive to 5FU and radiotherapy (RT). Conclusions ITGB4 is an effective diagnostic serum biomarker and a potential therapeutic target for CRC.

Keywords

• colorectal cancer
• CyTOF
• diagnosis biomarker
• ITGB4
• Single‐cell level