Elevated serum levels of transforming growth factor-beta 1 in patients with colorectal carcinoma - Its association with tumor progression and its significant decrease after curative surgical resection

BACKGROUND. Transforming growth factor-beta 1 (TGF-beta 1) acts as a potent inhibitor of cell growth and turner progression but loss of this negative regulation can contribute to tumor development. Some studies have reported an association between disease progression and TGF-beta 1 expression in pat ients with colorectal carcinoma, but their results were not always consiste nt. METHODS. Serum levels of TGF-beta 1 were measured using an enzyme-linked im munoadsorbent assay in 121 consecutive patients with colorectal carcinoma a nd compared with TGF-beta 1 serum levels in 31 healthy volunteers. Serum le vels of TGF-beta 1 also were measured in 50 patients who underwent curative surgical resection (part of the 121 preoperative patients) to compare thei r levels with preoperative serum levels of TGF-beta 1. RESULTS, Serum levels of TGF-beta 1 in patients with colorectal carcinoma ( 45 +/- 15 ng/mL) (mean +/- the standard deviation) were significantly highe r than those in the healthy control group (32 +/- 4 ng/mL) (P = 0.001). Ser um levels of TGF-beta 1 increased with increasing tumor stage (P < 0.01). S erum Levels of TGF-beta 1 were correlated significantly with depth of turne r invasion, lymph node metastasis, distant metastasis, and serum levels of carcinoembryonic antigen (CEA). Serum levels of TGF-beta 1 tended to increa se with increasing CEA (correlation coefficient = 0.21; P < 0.05). The mean serum level of TGF-beta 1 in patients with colorectal carcinoma before sur gery (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-beta 1 after tumo r resection decreased more significantly in patients with higher preoperati ve levels of TGF-PI (from 53 +/- 12 ng/mL to 36 +/- 6 ng/mL) (n = 30). CONCLUSIONS. The results of the current study suggest that serum levels of TGF-beta 1 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 whethe r serum levels of TGF-beta 1 carry significant clinical relevance. [See edi torial on pages 517-9, this issue]. Cancer 1999;85:554-61, (C) 1999 America n Cancer Society.