Clinical Value of Combined Determination of Serum B7-H4 with Carcinoembryonic Antigen, Osteopontin, or Tissue Polypeptide-Specific Antigen for the Diagnosis of Colorectal Cancer.

AIM

B7-H4 is member of the B7 family that negatively regulates the immune response, which are associated with tumor development and prognosis. The present study is aimed at examining serum B7-H4 expression and exploring its contribution to diagnosis in patients with colorectal cancer.

METHODS

We determined serum expressions of B7-H4, carcinoembryonic antigen (CEA), osteopontin (OPN), and tissue polypeptide-specific antigen (TPS) in 59 patients with colorectal cancer and 29 healthy volunteers and analyzed the diagnostic value of B7-H4 combined with CEA, OPN, or TPS detection for colorectal cancer. B7-H4, OPN, and TPS serum expressions were measured by enzyme-linked immunosorbent assay, and CEA was measured by electrochemical luminescence detection.

RESULTS

Serum B7-H4 levels were significantly higher in colorectal cancer patients compared with paired normal controls ( = 0.001). B7-H4 serum level was positively correlated with infiltration depth, tumor masses, and lymph node metastasis ( = 0.004, = 0.016, and = 0.0052, respectively). We also detected serum expression of B7-H4 before and after radical resection and showed that B7-H4 levels decreased significantly during the first week postoperation ( = 0.0064). We used receiver operating characteristic (ROC) curve analysis to indicate the potential diagnostic values of these markers. The areas under the ROC curves (AUC) for B7-H4, OPN, TPS, and CEA were 0.867, 0.805, 0.812, and 0.833, respectively. The optimal sensitivity and specificity of B7-H4 for discriminating between colon cancer patients and healthy controls were 88.2% and 86.7%, respectively, using a cut-off of value of 78.89 ng/mL. However, combined ROC analysis using B7-H4 and CEA revealed an AUC of 0.929, with a sensitivity of 98.9% and a specificity of 80.4% for discriminating colon cancer patients from healthy controls.

CONCLUSIONS

B7-H4 was highly expressed in the serum in colorectal cancer patients. Detection of B7-H4 plus CEA showed significantly increased sensitivity and specificity for discriminating between colorectal cancer patients and healthy controls compared to individual detection of these markers. Combined detection of serum B7-H4 and CEA may thus have the potential to become a new laboratory method for the early clinical diagnosis and prognostic evaluation of colorectal cancer.