Transmembrane serine protease 4 expression in the prognosis of radical resection for biliary tract cancer

Table 1 Patients’ characteristics (n = 85)

	TMPRSS4 expression		P value
	Positivity (n = 46)	Negativity (n = 39)
Age, median (range), years	75 (47-86)	75 (57-87)	0.612
Sex, male, n (%)	23 (50)	22 (56)	0.555
Neoadjuvant chemotherapy, n (%)	2 (4)	1 (2)	0.653
Preoperative CA19-9 level, median (range), U/mL	37 (0-27146)	13 (0-1246)	0.019
Diseases, n (%)
Perihilar cholangiocarcinoma	8 (17)	6 (15)	0.176
Distal cholangiocarcinoma	10 (22)	13 (34)
Gallbladder cancer	19 (41)	18 (46)
Ampulla of vater cancer	9 (20)	2 (5)
Operating time, median (range), min	465 (82-962)	425 (239-1052)	0.853
Operative blood loss, median (range), mL	310 (5-3950)	410 (5-1600)	0.609
Histology, tub1/tub2, n (%)	37 (80)	31 (79)	0.913
Tumor stage, pT3/T4, n (%)	14 (30)	10 (26)	0.624
Pathological tumor size, median (range), mm	35 (0-110)	25 (1-88)	0.081
Lymphatic invasion (ly), n (%)	16 (35)	6 (15)	0.039
Venous invasion (v), n (%)	20 (43)	14 (36)	0.477
Neural invasion (ne), n (%)	22 (48)	17 (44)	0.696
Tumor infiltrative type c (IFN c), n (%)	8 (17)	5 (13)	0.558
Lymph node metastasis, n (%)	24 (52)	16 (41)	0.304
Resection status, R0, n (%)	36 (78)	31 (80)	0.890
Adjuvant chemotherapy, n (%)	27 (59)	22 (56)	0.832

CA19-9: Carbohydrate antigen 19-9; tub1: Well-differentiated tubular adenocarcinoma; tub2: Moderately differentiated tubular adenocarcinoma.

Table 2 Univariate and multivariate overall survival analyses of poor prognostic factors (n = 85)

Factors	Univariate			Multivariate
	Total patients, (n = 85), n(%)	MST (months)	P value	HR	95%CI	P value
Age, years
< 80	62 (73)	37.8	0.718
≥ 80	23 (27)	58.7
Sex
Male	45 (53)	37.2	0.378
Female	40 (47)	46.5
Neoadjuvant chemotherapy
Yes	3 (4)	36.0	0.956
No	82 (96)	46.5
Preoperative CA 19-9 level, U/mL
< 37	55 (65)	46.5	0.504
≥ 37	30 (35)	43.4
TMPRSS4
Positivity	46 (54)	25.3	< 0.001	2.33	1.08-5.08	0.032
Negativity	39 (46)			1.0
Histology, tub1/tub2
Yes	68 (80)	46.5	0.752
No	17 (20)	36.0
Tumor stage, pT3/T4
Yes	24 (28)	22.0	0.002	2.26	1.06-4.81	0.035
No	61 (72)	59.4		1.0
Pathological tumor size, mm
< 30	43 (51)		0.017	1.0
≥ 30	42 (49)	33.7		1.32	0.65-2.65	0.439
Lymphatic invasion (ly)
Yes	22 (26)	16.3	< 0.001	1.33	0.62-2.84	0.461
No	63 (74)	75.3		1.0
Venous invasion (v)
Yes	34 (40)	22.0	< 0.001	1.93	0.91-4.07	0.086
No	51 (60)	59.4		1.0
Neural invasion (ne)
Yes	39 (46)	33.3	0.058	0.60	0.26-1.40	0.237
No	46 (54)	58.7		1.0
Tumor infiltrative type c (IFN c)
Yes	13 (15)	33.7	0.081	1.18	0.58-2.42	0.648
No	72 (85)	58.7		1.0
Lymph node metastasis
Yes	40 (47)	25.6	0.004	1.44	0.60-3.46	0.412
No	45 (53)	75.3		1.0
Resection status,
R0	67 (79)	46.6	0.022	1.0
R1	18 (21)	24.5		2.21	1.08-4.52	0.030
Adjuvant chemotherapy
Yes	49 (58)	36.0	0.229
No	36 (42)	75.3

CA19-9: Carbohydrate antigen 19-9; CI: Confidence interval; HR: Hazard ratio; MST: Median survival time; tub1: Well-differentiated tubular adenocarcinoma; tub2: moderately differentiated tubular adenocarcinoma; TMPRSS4: Transmembrane serine protease 4.

Table 3 Multivariate analyses of factors associated with transmembrane serine protease 4 positivity

Factors	Odds ratio (95%CI)	P value
Preoperative CA19-9 ≥ 37 U/mL	4.02 (1.30-12.47)	0.016
Pathological tumor size ≥ 30 mm	2.78 (1.05-7.30)	0.038
Lymphatic invasion (ly)	2.67 (0.84-8.53)	0.097
Neural invasion (ne)	0.45 (0.15-1.35)	0.153

CA19-9: Carbohydrate antigen 19-9; CI: Confidence interval; TMPRSS4: Transmembrane serine protease 4.