Abstract
ObjectiveTo explore the relationship between FABP4 and FABP6 expression and the pathogenesis of colorectal cancer (CRC) and their potential as biomarkers in the diagnosis of CRC.MethodsIn total, 100 CRC patients and 100 controls were enrolled. The serum levels of FABP4 and FABP6 were detected by enzyme-linked immunosorbent assay (ELISA) before and 2 weeks after radical resection of CRC. The protein expressions of FABP4 and FABP6 were observed in colorectal tumor tissues and adjacent tissues by immunohistochemistry and western blot, respectively. The diagnostic performance of FABP4 and FABP6 in patients with CRC was evaluated by receiver operating characteristic (ROC) curve analysis.ResultsThe serum levels of FABP4 and FABP6 in patients with CRC were higher than the levels in the controls before surgery (P < 0.001), and significantly decreased at 2 weeks after operation (P < 0.001). Immunohistochemistry showed that FABP4 and FABP6 were mainly distributed in the cytoplasm of human colorectal tumor tissues, and only a small amount distributed in adjacent tissues. Western blot revealed that the protein expressions of FABP4 and FABP6 were significantly higher in tumor tissues than in adjacent tissues (P < 0.001, P = 0.002, respectively). Tumors with high and low FABP4 and FABP6 expression have no significant correlation in tumor size, tumor site, distant organ and lymph node metastasis, histologic grade, lymphatic permeation, neurological invasion, vascular invasion, and Duke’s and TNM classification. Multivariate logistic regression analysis showed that FABP4 and FABP6 were independent risk factors for CRC (adjusted odds ratio 1.916; 95%CI 1.340–2.492; P < 0.001; adjusted odds ratio 2.162; 95%CI 1.046, 1.078); P < 0.001, respectively). In discriminating CRC from the normal control, the optimal sensitivity of FABP4 and FABP6 were 93.20% (95%CI 87.8–96.7) and 83.70% (95%CI 76.7–89.3), respectively, while the optimal specificity of FABP4 and FABP6 were 48.8% (95%CI 39.8–57.9) and 58.4% (95%CI 49.2–67.1), respectively. When combined detection of serum carcinoembryonic (CEA) and FABP4 and FABP6, the optimal sensitivity and specificity were 61.33% (95%CI 53.0–69.2) and 79.82% (95%CI 71.3–86.8), respectively.ConclusionIncreased expression of FABP4 and FABP6 not only were strong risk factors for the development of CRC but could also represent a potential biomarker for CRC diagnosis in Chinese patients. Combined detection of CEA with FABP4 and FABP6 could improve the diagnostic efficacy of CRC.
Highlights
Worldwide, the incidence of colorectal cancer (CRC) ranks third in malignant tumors and ranks second in terms of mortality [1]
In the CRC group before surgery, TCH (P = 0.003), low-density lipoprotein cholesterol (LDL-C) (P = 0.001), Fatty acid-binding protein 4 (FABP4) (P < 0.001), Fatty acid-binding protein 6 (FABP6) (P < 0.001), Carcinoembryonic antigen (CEA) (P = 0.001), CA19-9 (P = 0.004), and the distribution of the numbers of family history of CRC (P = 0.03) were all higher, but high-density lipoprotein cholesterol (HDL-C) was (P = 0.006) lower compared with the control group
The protein expression and localization of FABP4 and FABP6 in CRC tissues and adjacent tissues After immunohistochemical staining of the cancer tissue sections, it was observed under microscope that FABP4 and FABP6 were brown after staining, the positive sites were mainly distributed in cytoplasm of cells from human colorectal tumor tissues (FABP4: Fig. 2b, FABP6: Fig. 2d), and only a small amount was distributed in adjacent tissues (FABP4: Fig. 2a, FABP6: Fig. 2c)
Summary
The incidence of colorectal cancer (CRC) ranks third in malignant tumors and ranks second in terms of mortality [1]. Since FABPs were discovered in 1972, 12 different types (FABP1-12). According to the current literature, FABPs are expressed differently in different types of cancer or in different cell lines of the same cancer. FABP4 is mainly expressed in differentiated adipocytes and macrophages [5], and previous studies have focused on its association with metabolic syndrome and its related components, especially obesity [6]. Several investigations showed that FABP4 could promote cell growth and metastasis in breast and prostate cancers [8, 9]. These studies suggested that FABP4 might be involved in the development and progression of carcinoma
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