Table 1.

Research progress on the clinical utility of transforming growth factor-beta 1 as diagnostic marker against hepatocellular carcinoma

Ref.	Sample size HCC/control	Assay type	TGF-β1 level	Sample type	Outcome of the study
[60,61]	26/20	ELISA	Control: 1.4 ± 0.8 ng/mL	Plasma	TGF-β1 level showed a progressive elevation from cirrhotic to HCC patients to normal subjects. No significant association was found between plasma TGF-β1 and serum AFP levels
			HCC: 19.3 ± 1.95 ng/mL (P < 0.05)
[62,63]	70	ELISA	Control: 2.7 ± 0.7 ng/mL	Plasma	Elevated plasma TGF-β1 levels in HCC patients are associated with increased tumor size, overexpression of tissue inhibitor of metalloproteinase-1 and tumor severity
			HCC: 7.3 ± 4.3 ng/mL (P < 0.05)
[54,55]	94/50	125I-Radio Immuno Assay Kit	Control: 1.5-33.6 μg-1creatinine	Urine	Urinary TGF-β1 and serum AFP levels were higher in HCC than in cirrhotic patients. The study suggested that both TGF-β and AFP can be used as complementary biomarkers to distinguish between HCC and cirrhosis
			Cirrhotic: 4.3-52.5 μg-1creatinine
			HCC: 3.5-184 μg-1creatinine (P < 0.0001)
[64]	54/30	ELISA	TGF-β1 score	Serum	The study team calculated the serum concentration score based on the cut-off limit of 74 pg/mL and 637 pg/mL for TGF-β1 and sFas, respectively. TGF-β1 levels were higher than the cut off value in 23% HCC patients with negative AFP values, suggesting its diagnostic potential in AFP negative HCC
			Control: 0.6 ± 0.2
			HCC: 1.6 ± 0.5
[65]	38/23	ELISA	Control: 300 pg/mL	Plasma	Elevated plasma TGF-β1 level can be a useful diagnostic marker in detecting small HCC, with higher sensitivity than AFP
			HCC: 954.9 pg/mL (P < 0.0001)
[66]	70/32	ELISA	Control: 2 ng/mL	Plasma	Higher circulating TGF-β1 in HCC patients is associated with suppression of anti-tumor immunity and disease progression
			HCC: 7.5 ng/mL (P < 0.0001)
[52]	50/30	ELISA	Control: 0.67 ± 0.1 μg/mL	Serum	Aberrant TGF-β1 expression in HCC is associated with differentiation and worsening of HBV infection
			HCC: 2.21 ± 1.1 μg/mL (sensitivity = 89.5%, specificity = 94%)
		RT-PCR	Overexpression TGF-β1 mRNA in HCC patients, P < 0.0001		Circulating TGF-β1 level and TGF-β1 mRNA expression can be used as sensitive biomarkers for diagnosing HBV induced HCC
[56]	23/40	ELISA	Control: 14.35 ± 8.76 ng/mL	Serum	TGF-β1 is a sensitive diagnostic marker for HCC than AFP. Specificity can be increased with combined evaluation of TGF-β1 and AFP levels
			HCC: 64.35 ± 33.68 ng/mL (P < 0.05)
[67]	54/30	ELISA	Control: 39.5 ± 9.8 pg/mL	Serum	The study suggested elevated TGF-β1 and EGFR levels as reliable diagnostic markers for HCC induced, AFP negative HCC
			HCC: 1194 ± 331 pg/mL (P < 0.0001)
[68]	120/30	ELISA	Control: 250.16 ± 284.61 pg/mL	Serum	TGF-β1 showed progressive elevation during various stages of liver dysfunction. Higher TGF-β1 level in HCC is associated with tumor grade, pathological stage and invasiveness
			Cirrhotic: 487.98 ± 344.23 pg/mL
			HCC: 1687.47 ± 1642 pg/mL (P < 0.0001)
[69]	100/36	ELISA	Control: 57.29 ± 11.70 ng/mL	Serum	Serum levels of TGF-β were significantly higher in HCC patients than in normal controls
			HCC: 225.82 ± 48.93 ng/mL (P < 0.0001)

ELISA: Enzyme-linked immunosorbent assay; RT-PCR: Reverse transcription-polymerase chain reaction; HCC: Hepatocellular carcinoma; TGF-β: Transforming growth factor-beta; AFP: Alpha fetoprotein; HBV: Hepatitis B virus; EGFR: Epidermal growth factor receptor.