Elevated serum levels of transforming growth factor-beta1 in patients with colorectal carcinoma: its association with tumor progression and its significant decrease after curative surgical resection.

Abstract

Transforming growth factor-beta1 (TGF-beta1) acts as a potent inhibitor of cell growth and tumor progression but loss of this negative regulation can contribute to tumor development. Some studies have reported an association between disease progression and TGF-beta1 expression in patients with colorectal carcinoma, but their results were not always consistent. Serum levels of TGF-beta1 were measured using an enzyme-linked immunoadsorbent assay in 121 consecutive patients with colorectal carcinoma and compared with TGF-beta1 serum levels in 31 healthy volunteers. Serum levels of TGF-beta1 also were measured in 50 patients who underwent curative surgical resection (part of the 121 preoperative patients) to compare their levels with preoperative serum levels of TGF-beta1. Serum levels of TGF-beta1 in patients with colorectal carcinoma (45+/-15 ng/mL) (mean+/-the standard deviation) were significantly higher than those in the healthy control group (32+/-4 ng/mL) (P = 0.001). Serum levels of TGF-beta1 increased with increasing tumor stage (P < 0.01). Serum levels of TGF-beta1 were correlated significantly with depth of tumor invasion, lymph node metastasis, distant metastasis, and serum levels of carcinoembryonic antigen (CEA). Serum levels of TGF-beta1 tended to increase with increasing CEA (correlation coefficient = 0.21; P < 0.05). The mean serum level of TGF-beta1 in patients with colorectal carcinoma before surgery (45+/-14 ng/mL) (n = 50) significantly decreased to 34+/-7 ng/mL, which was within the normal range (32+/-4 ng/mL), after curative surgical resection of the tumor (P = 0.0000). Serum levels of TGF-beta1 after tumor resection decreased more significantly in patients with higher preoperative levels of TGF-beta1 (from 53+/-12 ng/mL to 36+/-6 ng/mL) (n = 30). The results of the current study suggest that serum levels of TGF-beta1 in colorectal carcinoma patients may be associated with disease progression and may be used as a biomarker in the management of colorectal carcinoma patients. The authors believe further studies with a large number of patients for a longer follow-up period are necessary to conclude whether serum levels of TGF-beta1 carry significant clinical relevance.