Expression and clinical significance of latent-transforming growth factor beta-binding protein 2 in primary hepatocellular carcinoma

Abstract

The present study aimed to explore the expression of latent transforming growth factor β binding protein 2 (LTBP2) in patients with hepatocellular carcinoma (HCC) and their correlation to clinicopathologial features.Serum levels of LTBP2 in 60 patients with HCC, 35 patients with hepatocellular benign tumors, 60 patients with precancerous lesions of HCC, and 60 healthy volunteers were determined by enzyme-linked immunosorbent assay. The expression levels of LTBP2 at messenger RNA (mRNA) and protein levels in 60 cases of HCC and adjacent tissues were detected by quantitative real-time polymerase chain reaction and immunohisochemistry. Statistical analysis was used to analyze the relationship between LTBP2 and clinical characteristics of patients with HCC.The mRNA and protein levels of LTBP2 were significantly upregulated in HCC tissues compared to adjacent tissues. Additionally, higher serum LTBP2 level was also observed in HCC patients relative to normal controls. Further investigation demonstrated that LTBP2 expression was associated with malignant degree of tumor, tumor progression, tumor differentiation, tumor size, tumor stage and hepatitis virus infection, and has prognostic implications in HCC patients.LTBP2 might be served as a potential biomarker in diagnosis and treatment of HCC.

Figure 1

Aberrant expression of LTBP2 in HCC patients. (A) The mRNA expression levels of LTBP2 determined by qRT-PCR in HCC tissues (n = 60) and adjacent nontumor tissues (n = 60); (B) Photographs of LTBP2 immunohistochemical staining in HCC tissues and adjacent non-tumor tissues; (C) The serum LTBP2 levels in patients with HCC and normal controls (n = 60) using ELISA; (D) Kaplan–Meier curves of survival rate differed between high and low LTBP2 expression in HCC patients. ^∗∗P < .01 versus adjacent nontumor tissues; ^#P < .05 versus normal controls. ELISA = enzyme-linked immunosorbent assay, HCC = hepatocellular carcinoma, LTBP2 = latent TGF-β binding protein 2, mRNA = messenger RNA, qRT-PCR = quantitative real time polymerase chain reaction.

Figure 2

Serum LTBP2 levels in patients with HCC according to clinicopathologic characteristics. (A) The serum LTBP2 levels in patients with HCC (n = 60), HCH (n = 15), FNH (n = 15) and HCA (n = 5) and normal controls (n = 60); (B) Serum LTBP2 in patients with HCC, high grade DNs (n = 20), LC (n = 20) and CHB (n = 20) and normal controls (n = 60); (C) Serum LTBP2 in HCC patients with well (n = 15), moderately (n = 18) and poorly (n = 27) differentiated tumors; (D) Serum LTBP2 in HCC patients with tumor size >3 cm (n = 25) and ≤3 cm (n = 35); (E) Serum LTBP2 in HCC patients at TNM stage I/II (n = 34) or III/IV (n = 26); (F) Serum LTBP2 in HCC patients with no hepatitis virus infection (n = 11), HBV infection (n = 34) and HCV infection (n = 15). ^∗P < .05 and ^∗∗P < .01. DNs = dysplastic nodules, CHB = chronic hepatitis B, FNH = focal nodular hyperplasia, HCA = hepatocellular adenoma, HCC = hepatocellular carcinoma, HCH = hepatic hemangioma, HCV = hepatitis C virus, LC = liver cirrhosis, LTBP2 = latent TGF-β binding protein 2, TNM = tumor–node-metastasis.

Figure 3

The mRNA LTBP2 expression in patients with HCC according to clinicopathologic characteristics. (A) LTBP2 mRNA expression in patients with HCC, high grade DNs (n = 20), LC (n = 20) and CHB (n = 20) and normal controls (n = 60); (B) LTBP2 mRNA in HCC patients with well (n = 15), moderately (n = 18) and poorly (n = 27) differentiated tumors; (C) LTBP2 mRNA in HCC patients with tumor size >3 cm (n = 25) and ≤3 cm (n = 35); (D) LTBP2 mRNA in HCC patients at TNM stage I/II (n = 34) or III/IV (n = 26); (E) LTBP2 mRNA in HCC patients with no hepatitis virus infection (n = 11), HBV infection (n = 34) and HCV infection (n = 15). ^∗∗P < .01. DNs = dysplastic nodules, CHB = chronic hepatitis B, HCA = hepatocellular adenoma, HCC = hepatocellular carcinoma, HCV = hepatitis C virus, LC = liver cirrhosis, LTBP2 = latent TGF-β binding protein 2, mRNA = messenger RNA, TNM = tumor–node-metastasis.