Prognostic Value Of Preoperative Systemic Inflammatory Biomarkers In Patients With Gallbladder Cancer And The Establishment Of A Nomogram

Figures & data

Table 1 Baseline Characteristics Of GBC Patients

Patient Characteristics	n/Median (Range)
Age (years)	64 (30–87)
Gender (male/female)	55/114
Hypertension (%)	36 (21.302%)
Diabetes mellitus (%)	13 (7.692%)
Liver cysts (%)	27 (15.976%)
Differentiation (well/moderate/poor)	29/68/72
Gallstones (%)	82 (48.521%)
Anemia (%)	51 (30.178)
T stage (T1/T2/T3/T4)	17/51/80/21
N stage (N0/N1/N2)	79/67/23
TNM (I/II/III/VI)	16/37/76/40
Death (%)	120 (71.006%)
Survival time	14 (1–97)
CEA (ng/mL)	4.14 (0.80–562.12)
Hemoglobin (g/L)	120 (60–166)
Monocyte (k/mm^2)	0.45 (0.01–2.17)
Lymphocyte (k/mm^2)	1.28 (0.19–3.51)
Albumin (g/dL)	38.80 (21.80–50.41)
Platelet (k/mm^2)	174 (37–525)
Leukocyte (k/mm^2)	5.80 (1.60–16.91)
Neutrophil (k/mm^2)	3.90 (1.00–15.20)
NLR	3.26 (0.83–44.32)
dNLR	2.03 (0.67–35.08)
PLR	145.21 (31.79–2282.61)
LMR	2.98 (0.43–234.00)

Note: The values are expressed as the median (range).

Abbreviations: TNM, tumor-node-metastasis; NLR, neutrophil to lymphocyte ratio; dNLR, derived neutrophil to lymphocyte ratio; PLR platelet to lymphocyte ratio; LMR, lymphocyte to monocyte ratio.

Figure 1 Optimal cut-off values for NLR (A), dNLR (B), PLR (C) and LMR (D) were applied with ROC curves for OS.

Table 2 Associations Of Inflammation-Based Markers With Clinicopathologic Characteristics Of GBC Patients

Variables	NLR		dNLR		PLR		LMR
	Median (Range)	P value	Median (Range)	P value	Median (Range)	P value	Median (Range)	P value
Total	3.26 (0.83–44.32)		2.03 (0.67–35.08)		145.21 (31.79–2282.61)		2.98 (0.43–234.00)
Age (years)		0.496		0.762		0.705		0.481
<60	3.46 (1.09–44.32)		2.09 (0.79–35.08)		154.89 (38.14–656.36)		3.14 (0.61–165.00)
≥60	3.09 (0.83–37.30)		2.03 (0.67–22.75)		141.41 (31.79–2282.61)		2.88 (0.43–234.00)
Gender		0.255		0.371		0.475		0.225
Male	3.64 (0.83–44.32)		2.18 (0.67–35.08)		146.56 (31.79–656.36)		3.27 (0.78–234.00)
Female	3.13 (0.85–38.00)		1.98 (0.75–22.75)		143.01 (38.14–2282.61)		2.81 (0.43–165.00)
Hypertension		0.869		0.985		0.942		0.727
Present	3.26 (0.85–44.32)		2.17 (0.75–35.08)		135.39 (31.79–380.00)		2.95 (0.85–12.40)
Absent	3.26 (0.83–38.00)		2.03 (0.67–22.75)		145.83 (38.14–2282.61)		3.02 (0.43–234.00)
Diabetes mellitus		0.916		0.974		0.516		0.054
Present	3.33 (1.40–5.98)		2.00 (0.97–4.16)		149.01 (31.79–342.52)		3.52 (1.86–165.00)
Absent	3.24 (0.83–44.32)		2.04 (0.67–35.08)		144.83 (38.14–2282.61)		2.89 (0.43–234.00)
CEA		0.960		0.767		0.553		0.068
≤3.14	3.31 (0.83–44.32)		2.00 (0.67–35.08)		151.46 (31.79–2282.61)		3.20 (0.43–234.00)
>3.14	3.24 (0.85–38.00)		2.07 (0.75–22.75)		139.93 (38.14–656.36)		2.68 (0.61–84.00)
Differentiation		0.009^#		0.008^#		0.024^#		0.002^#
Well	2.30 (0.85–30.33)		1.68 (0.75–22.75)		106.25 (45.83–458.54)		3.88 (1.33–18.00)
Moderate	3.30 (0.83–38.00)		2.04 (0.67–20.00)		141.95 (38.14–604.17)		3.05 (0.43–234.00)
Poor	3.56 (1.32–44.32)		2.26 (1.00–35.08)		159.74 (31.79–2282.61)		2.54 (0.61–165.00)
Gallstones		0.161		0.107		0.887		0.385
Present	2.97 (0.83–30.33)		1.95 (0.67–22.75)		145.33 (41.46–458.54)		3.12 (0.43–18.00)
Absent	3.36 (1.23–44.32)		2.21 (0.91–35.08)		144.44 (31.79–2282.61)		2.95 (0.61–234.00)
T stages		0.175		0.203		0.066		0.020^#
T1	2.36 (1.18–44.32)		1.78 (0.97–35.08)		97.86 (45.83–458.54)		3.88 (1.29–10.43)
T2	3.00 (0.83–38.00)		1.97 (0.67–22.75)		127.78 (31.79–604.17)		3.21 (1.03–234.00)
T3	3.78 (1.09–37.30)		2.31 (0.79–20.00)		160.05 (41.46–2282.61)		2.79 (0.43–165.00)
T4	3.18 (1.48–6.07)		1.90 (1.12–3.62)		158.72 (46.45–346.05)		2.51 (1.00–4.59)
N stages		0.184		0.203^#		0.012^#		0.001^#
N0	2.89 (0.85–44.32)		1.86 (0.75–35.08)		121.81 (31.79–656.36)		3.37 (1.03–234.00)
N1	3.40 (0.83–37.30)		2.13 (0.67–20.00)		148.42 (38.14–2282.61)		2.55 (0.43–165.00)
N2	3.90 (2.10–11.33)		2.49 (1.62–5.66)		191.51 (88.46–377.50)		2.42 (0.78–12.40)
TNM stages		0.292		0.404		0.035^#		0.002^#
I	2.33 (1.18–44.32)		1.73 (0.97–35.08)		97.66 (45.83–458.54)		4.02 (1.29–10.43)
II	2.77 (0.85–38.00)		1.78 (0.75–22.75)		120.00 (31.79–604.17)		3.73 (1.03–234.00)
III	3.62 (0.83–37.30)		2.14 (0.67–20.00)		148.72 (38.14–2282.61)		2.86 (0.43–165.00)
VI	3.28 (1.48–11.33)		2.22 (1.12–5.66)		166.91 (46.45–377.50)		2.43 (0.78–12.40)
Anemia		0.150		0.130		0.127		0.009^#
Present	3.20 (0.83–50.50)		2.23 (0.97–13.20)		148.42 (60.43–656.36)		2.50 (0.78–9.31)
Absent	3.58 (1.18–29.71)		1.89 (0.67–35.08)		143.47 (31.79–2282.61)		3.20 (0.43–234.00)
Liver cysts		0.761		0.879		0.918		0.685
Present	3.32 (0.83–44.32)		2.12 (0.92–9.49)		146.56 (66.18–282.26)		2.88 (1.19–12.40)
Absent	3.06 (1.15–15.91)		2.03 (0.67–35.08)		143.47 (31.79–2282.61)		3.04 (0.43–234.00)
Death		0.001^#		0.001^#		0.039^#		0.020^#
Present	3.54 (0.85–38.00)		2.22 (0.75–22.75)		153.01 (31.79–2282.61)		2.68 (0.43–165.00)
Absent	2.29 (0.83–44.32)		1.64 (0.67–35.08)		114.39 (60.43–458.54)		3.20 (1.30–234.00)

Note: ^#P value < 0.050. P value of less than 0.050 was considered to indicate significant difference. The P value was calculated by nonparametric Wilcoxon rank-sum test.

Abbreviations: TNM, tumor-node-metastasis; NLR, neutrophil to lymphocyte ratio; dNLR, derived neutrophil to lymphocyte ratio; PLR platelet to lymphocyte ratio; LMR, lymphocyte to monocyte ratio.

Figure 2 Kaplan-Meier curves for cumulative OS of the study population (A) and OS of patients stratified according to tumor differentiation (B) and TNM stage (C).

Figure 3 Kaplan-Meier curves for overall survival probability according to the preoperative NLR (A), dNLR (B), PLR (C), and LMR (D), respectively.

Table 3 Univariate Cox Proportional Hazards Regression Analysis For Overall Survival (OS) In Patients With Gallbladder Carcinoma (GBC)

Variables	Factors	Univariate Analysis		Multivariate Analysis
		HR (95% CI)	P value	HR (95% CI)	P value
Age (years)	≥60 vs <60	0.928 (0.622–1.382)	0.712
Gender	Male vs Female	1.054 (0.718–1.548)	0.787
Hypertension	Present vs Absent	1.180 (0.956–1.456)	0.124
Diabetes mellitus	Present vs Absent	1.234 (0.644–2.364)	0.527
CEA (ng/mL)	>3.14 vs ≤3.14	1.463 (1.011–2.118)	0.044^#	1.704 (1.156–2.513)	0.007^#
Differentiations	Per 1 degree increase	2.029 (1.560–2.639)	<0.001^#	1.459 (1.064–2.002)	0.019^#
Liver cysts	Present vs Absent	0.789 (0.458–1.359)	0.393
Gallstones	Present vs Absent	0.950 (0.661–1.368)	0.784
Anemia	Present vs Absent	1.233 (0.834–1.822)	0.293
T stage	Per 1 stage increase	2.278 (1.773–2.928)	<0.001^#	1.850 (1.389–2.463)	< 0.001^#
N stage	Per 1 stage increase	2.166 (1.680–2.792)	<0.001^#	1.516 (1.116–2.059)	0.008
TNM stage	Per 1 stage increase	2.190 (1.734–2.765)	<0.001^#	NG	NG
NLR	≥2.61 vs <2.61	2.268 (1.525–3.373)	<0.001^#	3.298 (1.359–8.000)	0.008^#
dNLR	≥1.78 vs <1.78	1.906 (1.294–2.808)	0.001^#	0.494 (0.217–1.126)	0.093
PLR	≥145.33 vs <145.33	2.152 (1.485–3.118)	<0.001^#	1.221 (0.785–1.899)	0.376
LMR	<2.66 vs ≥2.66	2.048 (1.421–2.951)	<0.001^#	1.549 (1.051–2.283)	0.027^#

Note: ^#P value < 0.050. P value of less than 0.050 was considered to indicate significant difference. The P value was calculated by nonparametric Wilcoxon rank-sum test.

Abbreviations: HR, hazard ratio; CI, confidence interval; TNM, tumor-node-metastasis; NLR, neutrophil to lymphocyte ratio; dNLR, derived neutrophil to lymphocyte ratio; PLR platelet to lymphocyte ratio; LMR, lymphocyte to monocyte ratio; NG, none given.

Figure 4 Nomogram for predicting 1-, 3-, and 5-year OS of GBC patients after radical cholecystectomy (A). Calibration plot of the nomogram for 1-year (B), 3-year (C), and 5-year survival (D). The red line represents the “ideal” line of a perfect match between predicted and observed survival. The black line indicates the performance of the proposed nomogram. The X-axis is nomogram predicted probability of survival and Y-axis is actual survival. Black dots are sub-cohorts of the data set; vertical bars represent 95% confidence interval.