Soluble cytotoxic T-lymphocyte antigen 4: a favorable predictor in malignant tumors after therapy

Figures & data

Table 1 Characteristics of cancer patients (N=141)

Features	No of patients (%)
	RT	Chemotherapy	CRT	Total
Overall	57 (40.43)	46 (32.62)	38 (26.95)	141
Gender
Female	22 (15.60)	19 (13.48)	16 (11.35)	57 (40.43)
Male	35 (24.82)	27 (19.15)	22 (15.60)	84 (59.57)
Age (years)
≤65	28 (19.86)	23 (16.31)	23 (16.31)	74 (52.48)
.65	29 (20.57)	23 (16.31)	15 (10.64)	67 (47.52)
Tobacco smoking
Ever	18 (12.77)	13 (9.22)	15 (10.64)	46 (32.62)
Never	39 (27.66)	33 (23.40)	23 (16.31)	95 (67.38)
Alcohol drinking
Ever	34 (24.11)	25 (17.73)	26 (18.44)	85 (60.28)
Never	23 (16.31)	21 (14.89)	12 (8.51)	56 (39.72)
Type
Lung cancer	16 (11.35)	18 (12.77)	23 (16.31)	57 (40.43)
Esophageal cancer	25 (17.73)	7 (4.96)	9 (6.38)	41 (29.08)
Liver cancer	9 (6.38)	4 (2.84)	3 (2.13)	16 (11.35)
Ovarian cancer	4 (2.83)	6 (4.26)	9 (6.38)	19 (13.48)
Cervical cancer	3 (2.13)	3 (2.13)	2 (1.42)	8 (5.67)
Stage
II–III	23 (16.31)	14 (9.93)	24 (17.02)	61 (43.26)
IV	34 (24.11)	32 (22.70)	14 (9.93)	80 (56.74)
Lymph node metastasis
Yes	23 (16.31)	13 (9.22)	18 (12.77)	54 (38.30)
No	34 (24.11)	33 (23.40)	20 (14.18)	87 (61.70)
Distant metastasis
Yes	27 (19.15)	10 (7.09)	21 (14.89)	58 (41.13)
No	30 (21.28)	36 (2.53)	17 (12.06)	83 (58.87)

Abbreviations: CRT, chemoradiotherapy; RT, radiotherapy.

Figure 1 Level of sCTLA-4 in all 4 groups.

Notes: Compared with the level of sCTLA-4 1 day before therapies, sCTLA-4 levels during therapies were significantly higher among all these 4 subgroups including the (A) RT, (B) chemotherapy, (C) CRT, and (D) whole patient group (all P<0.05).
Abbreviations: CRT, chemoradiotherapy; RT, radiotherapy; sCTLA-4, soluble cytotoxic T-lymphocyte antigen 4.

Figure 2 Survival curves for OS in all 4 groups.

Notes: Survival analysis was according to sCTLA-4 levels during therapy, with green indicating upregulated sCTLA-4 levels and blue denoting downregulated sCTLA-4 levels. Patients in the (A) RT, (B) chemotherapy, (C) CRT, and (D) whole patient groups with upregulated sCTLA-4 levels had longer OS than patients with downregulated sCTLA-4 levels (all P<0.05, log-rank test).
Abbreviations: CRT, chemoradiotherapy; OS, overall survival; RT, radiotherapy; sCTLA-4, soluble cytotoxic T-lymphocyte antigen 4.

Figure 3 Survival curves for PFS in all 4 groups.

Notes: Survival analysis was according to sCTLA-4 levels during therapy, with green indicating upregulated sCTLA-4 levels and blue denoting downregulated sCTLA-4 levels. Patients in the (A) RT, (B) chemotherapy, (C) CRT, and (D) whole patient groups with upregulated sCTLA-4 levels had longer PFS than patients with downregulated sCTLA-4 levels (all P<0.05, log-rank test).
Abbreviations: CRT, chemoradiotherapy; PFS, progression-free survival; RT, radiotherapy; sCTLA-4, soluble cytotoxic T-lymphocyte antigen 4.

Table 2 Details of the Cox proportional hazard model for all 4 groups

Factor	RT group		Chemotherapy group		CRT group		Whole patient group
	P-value	HR (95% CI)	P-value	HR (95% CI)	P-value	HR (95% CI)	P-value	HR (95% CI)
Age	0.591	0.787 (0.327–1.889)	0.031	0.292 (0.095–0.893)	0.897	0.943 (0.388–2.291)	0.644	0.897 (0.567–1.420)
Gender	0.624	1.295 (0.461–3.643)	0.717	0.823 (0.287–2.363)	0.995	1.003 (0.373–2.702)	0.966	0.989 (0.595–1.644)
Lymphocyte metastasis	0.346	0.629 (0.239–1.651)	0.719	1.389 (0.231–8.352)	0.038	0.353 (0.132–0.944)	0.009	0.481 (0.277–0.835)
Distant metastasis	0.568	1.292 (0.536–3.119)	0.280	0.312 (0.038–2.579)	0.248	1.221 (0.453–3.293)	0.974	1.008 (0.608–1.672)
TNM stage	0.007*	0.190 (0.057–0.633)	0.013*	0.163 (0.039–0.681)	0.026*	0.121 (0.019–0.773)	0.000*	0.222 (0.122–0.402)
sCTLA-4	0.049*	0.385 (0.149–0.996)	0.016*	0.311 (0.121–0.802)	0.010*	0.061 (0.007–0.517)	0.000*	0.287 (0.166–0.493)
WBC change	0.537	1.522 (0.402–5.761)	0.892	0.922 (0.285–2.984)	0.186	0.489 (0.169–1.413)	0.998	0.999 (0.568–1.758)
NEU change	0.777	0.865 (0.315–2.371)	0.679	1.252 (0.433–3.620)	0.705	0.851 (0.369–1.963)	0.729	0.922 (0.580–1.464)
LYM change	0.209	0.550 (0.216–1.398)	0.066	3.219 (0.924–11.215)	0.584	0.732 (0.239–2.239)	0.115	0.681 (0.422–1.098)
MON change	0.325	0.480 (0.111–2.068)	0.148	0.362 (0.091–1.433)	0.161	2.688 (0.674–10.715)	0.827	0.938 (0.528–1.666)

Notes: HR and 95% CI were listed. TNM stage and high sCTLA-4 level were independent prognostic factors.

* P<0.05.

Abbreviations: CI, confidence interval; CRT, chemoradiotherapy; HR, hazard ratio; LYM, lymphocyte; MON, monocyte; NEU, neutrophil; RT, radiotherapy; sCTLA-4, soluble cytotoxic T-lymphocyte antigen 4; TNM, tumor node metastisis; WBC, white blood cell.

Table 3 Spearman’s rho analyses for consistency between sCTLA-4 and clinicopathological factors

Clinicopathological factor	Correlation coefficient	P-value
Age	−0.083	0.325
Gender	−0.088	0.302
TNM stage	−0.405	0.000*
Therapy	−0.079	0.350
Distant metastasis	−0.137	0.106
Lymph node metastasis	−0.181	0.031*
WBC change	−0.161	0.056
NEU change	0.093	0.271
LYM change	−0.032	0.710
MON change	−0.107	0.205

Notes: Of all the clincopathological factors evaluated in this research, TNM stage and lymph node metastasis were correlated with sCTLA-4 level in whole patient group.

* P<0.05.

Abbreviations: CI, confidence interval; HR, hazard ratio; LYM, lymphocyte; MON, monocyte; NEU, neutrophil; sCTLA-4, soluble cytotoxic T-lymphocyte antigen 4; TNM, tumor node metastasis; WBC, white blood cell.