Serum hepatitis B viral (HBV) DNA is a predictive biomarker for survival in non-small cell lung cancer patients with chronic HBV infection

Figures & data

Table 1 Baseline clinical and characteristics of patients

Characteristic	No.	%
Gender
Male	144	76.6
Female	44	23.4
Age (years)
<56	87	46.3
≥56	101	53.7
Family history
Yes	43	22.9
No	145	77.1
Smoking
Yes	114	60.6
No	74	39.4
TNM stage^a
I	41	21.8
II	19	10.1
III	73	38.8
IV	55	29.3
Histological type
Adenocarcinoma	119	63.3
Squamous cell carcinoma	62	33.0
Other	7	3.7
Size (cm)^b
<4.0	72	38.3
≥4.0	116	61.7
Treatment
Surgery	42	22.3
Surgery and radiotherapy/chemotherapy	63	33.5
Radiotherapy/chemotherapy	61	32.4
Other	22	11.8
HBV DNA, copies/mL
<10^3	60	31.9
10^3–9,999	49	26.1
10^4–99,999	30	16.0
10^5–999,999	22	11.7
≥10^6	27	14.3
ALB (g/L)
<42.0	86	45.7
≥42.0	102	54.3
CRP (mg/L)
<4.0	87	46.3
≥4.0	101	53.7
Platelet (10^9/L)
<229	93	49.5
≥229	95	50.5
NLR
<2.23	94	50.0
≥2.23	94	50.0
PLR
<121.5	94	50.0
≥121.5	94	50.0
GPS
0	128	68.1
1	53	28.2
2	7	3.7

Notes: ^aTNM stage was classified according to the AJCC 7th TNM staging system; ^bThe tumor maximum diameter.

Abbreviations: TNM, pathological tumor node metastasis stage; ALB, albumin; CRP, C-reactive protein; NLR, neutrophil–lymphocyte ratio; PLR, platelet–lymphocyte ratio; GPS, Glasgow prognostic score; AJCC, American Joint Committe on cancer.

Table 2 Univariable and multivariable analysis for OS

Variable	Univariable analysis		Multivariable analysis
HR (95% CI)	P	HR (95% CI)	P
Gender			-	-
Male	Reference
Female	0.86 (0.54–1.39)	0.548
Age (years)			-	-
<56	Reference
≥56	0.75 (0.50–1.12)	0.159
Family history			-	-
Yes	Reference
No	1.04 (0.64–1.67)	0.879
Smoking			-	-
Yes	Reference
No	1.05 (0.69–1.58)	0.834
TNM stage			1.36 (1.03–1.78)	0.028
I	Reference
II	2.27 (0.89–5.75)	0.085
III	3.25 (1.61–6.57)	0.001
IV	7.31 (3.60–14.84)	<0.001
Histological type			-	-
Adenocarcinoma	Reference
Squamous cell carcinoma	0.96 (0.62–1.48)	0.845
Other	2.00 (0.73–5.52)	0.179
Size (cm)			-	-
<4.0	Reference
≥4.0	1.83 (1.18–2.84)	0.007
Treatment			1.57 (1.17–2.09)	0.002
Surgery	Reference
Surgery and radiotherapy/chemotherapy	0.86 (0.45–1.640)	0.639
Radiotherapy/chemotherapy	3.21 (1.77–5.83)	<0.001
Other	6.61 (3.29–13.30)	<0.001
HBV DNA, copies/mL
<103	Reference		1.43 (1.23–1.67)	<0.001
103–9,999	2.00 (1.09–3.70)	0.026
104–99,999	2.54 (1.34–4.82)	0.004
105–999,999	4.23 (2.06–8.72)	<0.001
≥106	6.11 (3.23–11.56)	<0.001
ALB (g/L)			-	-
<42.0	Reference
≥42.0	0.60 (0.40–0.90)	0.012
CRP (mg/L)			-	-
<4.0	Reference
≥4.0	2.00 (1.31–3.01)	0.001
Platelet (109/L)
<229	Reference
≥229	1.13 (0.75–1.69)	0.562
NLR			-	-
<2.23	Reference
≥2.23	1.58 (1.05–2.37)	0.027
PLR			-	-
<121.5	Reference
≥121.5	1.29 (0.86–1.93)	0.217
GPS			1.69 (1.07–2.69)	0.026
0	Reference
1	2.31 (1.51–3.54)	<0.001
2	2.35 (0.94–5.88)	0.068

Abbreviations: HR, hazard ratio; 95% CI, 95% confidence interval; TNM, Pathological Tumor Node Metastasis stage; ALB, albumin; CRP, C-reactive protein; NLR, neutrophil-lymphocyte ratio; PLR, platelet-lymphocyte ratio; GPS, Glasgow prognostic score.

Figure 1 Cox regression forest plot of independent prognostic factors in NSCLC patients with chronic HBV infection.

Abbreviations: HBV, hepatitis B viral; GPS, Glasgow Prognostic Score; NSCLC, non-small cell lung cancer.

Figure 2 Kaplan–Meier estimates of 1-, 3-, and 5-year survival and OS for NSCLC patients with different HBV DNA levels. (A) 1-year survival; (B) 3-year survival; (C) 5-year survival; (D) OS for NSCLC patients.Abbreviations: HBV, hepatitis B viral; NSCLC, non-small cell lung cancer; OS, overall survival.

Figure 3 Nomogram model predicting 1-, 3- and 5-year survival in NSCLC patients with chronic HBV infection. Abbreviations: GPS, Glasgow Prognostic Score; HBV, hepatitis B viral; NSCLC, non-small cell lung cancer; Rad/che, radiotherapy/chemotherapy.

Table 3 The C-index of independent factors and nomogram for prediction of OS*

Factor	C-index (95% CI)	P
Nomogram*	0.76 (0.72–0.81)
TNM stage	0.69 (0.64–0.73)
Treatment	0.68 (0.63–0.74)
HBV DNA	0.67 (0.61–0.72)
GPS	0.61 (0.56–0.66)
HBV DNA vs nomogram		<0.001
TNM stage vs nomogram		<0.001
HBV DNA vs treatment		0.50
HBV DNA vs GPS		0.12
HBV DNA vs TNM stage		0.48

Note: *Nomogram: including four risk factors (TNM, treatment, HBV DNA, and GPS).

Abbreviations: C-index, concordance index; GPS, Glasgow Prognostic Score; HBV, hepatitis B viral; OS, overall survival.

Figure 4 Time-dependent ROC analysis of TNM, treatment, HBV DNA, and GPS. Abbreviations: AUC, area under the curve; GPS, Glasgow Prognostic Score; HBV, hepatitis B viral; ROC, receiver operating characteristic.