The prognostic value of C-reactive protein/albumin ratio in human malignancies: an updated meta-analysis

Figures & data

Figure 1 Flow diagram of searching relevant studies for this meta-analysis.

Table 1 Characteristics of studies included in this meta-analysis

Author	Year	Country	Study sample size (M/F)	Mean/median age (years)	Cancer stage	Cancer sites	Cut-off value for CAR (> CV/, CV)	Major treatment	Study end points	HR with its 95% CI	Source	Follow-up time (months)
Park et al^Citation13	2016	Korea	40 (27/13)	Mean 66 (31–83)	I–IV (AJCC)	Oral	0.085 (13/27)	Resection	OS	OS (M), 6.08 (1.97–18.74)	Direct	Mean 35.58
Li et al^Citation14	2016	China	409 (288/121)	Median 45 (18–77)	I–IV (AJCC)	Nasopharynx	0.037 (228/181)	Multiple	OS, 5-year survival rate	OS (M), 2.09 (1.22–3.59)	Direct	>60
Zhang et al^Citation15	2016	China	1,572 (1,172/400)	Median 45 (14–78)	I–IV (AJCC)	Nasopharynx	0.05 (614/958)	Multiple	OS, DFS	OS (M), 1.39 (1.00–1.94) DFS (M), 1.24 (0.97–1.57)	Direct Direct	Median 50.0 (1.4–76.4)
Tao et al^Citation16	2016	China	719 (495/224)	Median 48 (14–81)	I–IV (AJCC)	Nasopharynx	0.141 (341/378)	Radiotherapy	OS, 5-year survival rate	OS (M), 2.17 (1.13–3.06)	Direct	>60
He et al^Citation17	2016	China	2,685 (2,535/150)	NA	I–III (NA)	Nasopharynx	0.064 (1,022/1,663)	Multiple	OS, DFS, 5-year survival rate	OS (M), 1.36 (1.11–1.65)	Direct	Median 46.30 (0.07–188.43)
Yu et al^Citation18	2017	China	129	Median 61 (29–82)	I–IV (AJCC)	Laryngeal	0.047 (56/73)	Multiple	OS, DFS	OS (M), 2.13 (1.15–3.93) DFS (M), 2.36 (1.28–4.36)	Direct Direct	Median 77 (66–94)
Zhang et al^Citation19	2017	China	617 (461/156)	Median 60 (30–82)	I–III (clinical stage)	Lung	0.424 (125/492)	Resection	OS, DFS	OS (M), 1.87 (1.41–2.49) DFS (M), 1.54 (1.10–2.16)	Direct Direct	Median 50 (1–108)
Miyazaki et al^Citation20	2016	Japan	108 (69/39)	Median 82	I–IV (clinical stage)	Lung	0.028 (49/59)	Resection	OS, 5-year survival rate	OS (M), 2.13 (1.07–4.30)	Direct	>60
Zhou et al^Citation21	2015	China	367 (316/51)	Median 59 (23–82)	Limited/extensive	Lung	0.441 (128/239)	Multiple	OS	OS (M), 1.34 (1.04–1.73)	Direct	Median 29.40 (0.03–116.07)
Wei et al^Citation22	2015	China	423 (341/82)	Median 58 (24–88)	I–IV (AJCC)	Esophageal	0.095 (147/276)	Resection	OS	OS (M), 1.39 (1.03–1.88)	Direct	Median 35.7 (0.6–95.6)
Xu et al^Citation23	2015	China	468 (416/52)	Median 58	I–IIIC (AJCC)	Esophageal	0.50 (87/381)	Resection	OS, 5-year survival rate	OS (M), 2.44 (1.82–3.26)	Direct	>36
Liu et al^Citation24	2015	China	455 (314/141)	Median 59 (19–86)	I–III (AJCC)	Gastric	0.25 (302/153)	Resection	OS, 5-year survival rate	OS (M), 1.63 (1.19–2.20)	Direct	Median 25 (1–76)
Toiyama et al^Citation25	2016	Japan	384 (264/120)	Median 67 (32–88)	I–III (JC)	Gastric	0.051 (NA)	Resection	OS, DFS	OS (M), 2.21 (1.19–4.11) DFS (M), 1.82 (1.03–3.23)	Direct Direct	Median 47.6 (40.1–54.1)
Shibutani et al^Citation26	2016	Japan	99 (57/42)	63 (27–86)	Unresectable	Colorectal	0.183 (36/63)	Chemotherapy	OS	OS (M), 1.87 (1.06–3.30)	Direct	Up to 60
Shibutani et al^Citation27	2016	Japan	705 (411/294)	Median 68 (26–90)	I–III (JC)	Colorectal	0.028 (358/347)	Resection	OS, DFS, 5-year survival rate	OS (U), 1.76 (1.17–2.64) DFS (U), 1.50 (1.05–2.14)	Curve Direct	>60
Ishizuka et al^Citation28	2015	Japan	627 (400/227)	NA	0–IV (JC)	Colorectal	0.038 (366/261)	Resection	OS	OS (M), 2.61 (1.62–4.21)	Direct	Median 30
Tominaga et al^Citation29	2016	Japan	136 (79/57)	NA	T1–4 N1–3	Colorectal	0.1 (30/106)	Resection	OS, DFS	OS (U), 0.96 (0.87–1.06) DFS (M), 4.43 (1.94–10.15)	Data Direct	Up to 110
Li and Zhang^Citation30	2016	China	178 (127/51)	Mean 67.9	NA	Hepatic	0.46 (97/86)	Resection	OS	OS (M), 2.52 (1.82–3.47)	Direct	Mean 35.6 (19–55)
Kinoshita et al^Citation31	2015	Japan	186 (133/53)	Median 72	0–D (BCLC)	Hepatic	0.037 (102/84)	Resection	OS	OS (M), 3.39 (1.99–5.80)	Direct	Median 18 (1–88)
Liu et al^Citation32	2017	China	386 (238/148)	Median 61 (34–83)	I–IV (AJCC)	Pancreatic	0.180 (91/295)	Resection	OS	OS (M), 2.07 (1.59–2.70)	Direct	Median 8.7
Wu et al^Citation33	2016	China	233 (156/77)	Median 62 (26–85)	Advanced	Pancreatic	0.54 (74/159)	Multiple	OS	OS (M), 4.00 (2.64–6.03)	Direct	Up to 12
Haruki et al^Citation34	2016	Japan	113 (70/43)	Median 66.8 (27–85)	I–IV (clinical)	Pancreatic	0.03 (58/53)	Resection	OS, DFS	OS (M), 1.73 (1.04–2.87) DFS (U), 1.54 (1.00–2.37)	Direct Direct	>60
Lee et al^Citation35	2016	Korea	82 (49/33)	Mean 63.5±10.7	Advanced/metastatic	Pancreatic	0.5 (40/42)	Chemotherapy	OS	OS (M), 1.60 (0.84–3.04)	Direct	Up to 24
Chen et al^Citation36	2015	China	406 (253/153)	Median 58 (24–80)	I–IV (clinical stage)	Kidney	0.15 (93/313)	Resection	OS	OS (U), 3.44 (2.43–4.86)	Curve	Mean 63 (1–151)
Guo et al^Citation37	2017	China	570 (382/188)	Mean 51.43±13.52	I–IV (TNM stage)	Kidney	0.085 (393/177)	Resection	OS, DFS	OS (M), 1.94 (1.12–3.36) DFS (M), 2.14 (1.22–3.75)	Direct	Median 63.54

Notes: Multiple: multidisciplinary treatments; Data: available data to calculate HR with corresponding CI; Curve: Kaplan–Meier curve.

Abbreviations: M/F, male/female; CAR, C-reactive protein/albumin ratio; CV, cut-off value; HR, hazard ratio; CI, confidence interval; AJCC, American Joint Committee on Cancer; OS, overall survival; M, multivariate analysis; DFS, disease-free survival; NA, not available; JC, Japanese Classification; U, univariate analysis; BCLC, Barcelona Clinic Liver Cancer.

Figure 2 Forest plots for the prognostic impact of CAR on overall survival in human malignancies. Studies were grouped by cut-off value of CAR, and the median value was 0.095.

Note: Weights are from random-effects analysis.
Abbreviations: CAR, C-reactive protein/albumin ratio; HR, hazard ratio; CI, confidence interval.

Figure 3 Forest plots for the prognostic impact of C-reactive protein/albumin ratio on disease-free survival in human malignancies.

Abbreviations: HR, hazard ratio; CI, confidence interval.

Figure 4 Forest plots for the prognostic impact of C-reactive protein/albumin ratio on 5-year mortality in human malignancies.

Note: Weights are from random-effects analysis.
Abbreviations: OR, odds ratio; CI, confidence interval.

Figure 5 Forest plots for subgroup analysis based on the meta-analysis with overall survival according to different cancer types.

Note: Weights are from random-effects analysis.
Abbreviations: HR, hazard ratio; CI, confidence interval.

Table 2 Subgroup analysis for the prognostic impact of C-reactive protein/albumin ratio on overall survival in human malignancies

Variables	No of studies	No of patients	HR (95% CI)	P-value	Heterogeneity
					I^2 (%)	P-value
Total	25	12,097	1.99 (1.65–2.40)	0.000	86.9	0.000
Publication year
2016–2017	18	9,165	1.93 (1.54–2.42)	0.000	86.6	0.000
2014–2015	7	2,932	2.11 (1.56–2.84)	0.000	81.6	0.000
Country
China	15	9,617	1.97 (1.66–2.34)	0.000	75.3	0.000
Others	10	2,480	2.03 (1.38–2.97)	0.000	86.4	0.000
Sample size
≥386	14	10,426	1.91 (1.64–2.24)	0.000	63.5	0.001
<386	11	1,671	2.10 (1.45–3.04)	0.000	90.6	0.000
Cut-off value for CAR
>0.095	12	4,146	2.00 (1.47–2.72)	0.000	92.7	0.000
≤0.095	13	7,951	1.88 (1.57–2.25)	0.000	51.5	0.016
Cancer sites
Nasopharynx	4	5,385	1.56 (1.25–1.94)	0.000	35.8	0.197
Esophagus	2	891	1.84 (1.06–3.20)	0.030	85.6	0.008
Lung	3	1,092	1.63 (1.24–2.15)	0.046	45.4	0.160
Stomach	2	839	1.73 (1.31–2.28)	0.000	0.0	0.388
Liver	2	364	2.73 (2.07–3.60)	0.000	0.0	0.352
Pancreas	4	814	2.25 (1.52–3.34)	0.000	69.8	0.019
Colorectum	4	1,567	1.64 (0.96–2.80)	0.069	89.0	0.000
Kidney	2	976	2.69 (1.54–4.69)	0.000	66.5	0.084
Others	2	169	3.22 (1.18–8.80)	0.022	61.0	0.109
Treatments
Resection	16	5,802	2.08 (1.60–2.71)	0.000	90.1	0.000
Others	9	6,295	1.82 (1.43–2.33)	0.000	70.9	0.001

Abbreviations: HR, hazard ratio; CI, confidence interval; CAR, C-reactive protein/albumin ratio.

Figure 6 Sensitivity analysis for the studies included in the meta-analysis with overall survival in human malignancies.

Abbreviation: CI, confidence interval.

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