Table 2.

Univariable and multivariable analysis for DFS in the discovery set and the two external validation sets

	Discovery set		Validation set V1		Validation set V2
	HR (95%CI)	p	HR (95%CI)	p	HR (95%CI)		p
Univariable analysis
Age
> 65 years vs. ≤ 65 years	1.32(0.93–1.86)	0.115	1.02(0.60–1.71)	0.953	0.80(0.47–1.37)		0.410
Sex
Female vs. Male	0.64(0.45–0.91)	0.012	0.69(0.46–1.02)	0.061	0.62(0.41–0.94)		0.025
Smoking status
Ever vs. Never	1.72(1.20–2.47)	0.003	1.25(0.81–1.93)	0.316	1.32(0.88–1.97)		0.181
Tumor site
Lower vs. Upper/Middle	0.87(0.60–1.27)	0.482	1.33(0.88–2.01)	0.182	0.95(0.63–1.44)		0.820
Family history
Yes vs. No	1.20 (0.71–2.02)	0.503	1.25(0.58–2.70)	0.574	0.23(0.03–1.64)		0.142
Differentiation
G3/G4 vs. G1/G2	3.03(2.12–4.33)	<0.001	2.07(1.38–3.12)	<0.001	1.76(1.18–2.64)		0.006
TNM stage
II vs. I	2.58(1.61–4.14)	<0.001	2.00(1.18–3.39)	0.010	2.43(1.41–4.20)		0.001
III vs. I	5.51(3.69–8.22)	<0.001	5.95(3.71–9.54)	<0.001	4.25(2.66–6.77)		< 0.001
VPI
Yes vs. No	1.42(1.01–2.00)	0.042	1.06(0.71–1.59)	0.759	1.72(1.00–2.96)		0.051
LVI
Yes vs. No	4.37(2.54–7.53)	<0.001	2.96(0.41–21.36)	0.281	2.05(0.94–4.43)		0.070
Type of surgery
Segmentectomy/Wedge vs.	0.87(0.48–1.57)	0.644	1.14(0.46–2.81)	0.775	1.61(0.65–3.97)		0.300
Lobectomy/Pneumonectomy
Adjuvant chemotherapy
Yes vs. No	3.85(2.71–5.47)	<0.001	2.31(1.53–3.50)	<0.001	3.06(1.97–4.74)		< 0.001
Immune phenotypes
IP2 vs. IP1	0.57(0.38–0.86)	0.007	0.52(0.30–0.90)	0.019	0.37(0.21–0.64)		< 0.001
IP3 vs. IP1	0.50(0.33–0.76)	0.001	0.43(0.21–0.86)	0.016	0.37(0.18–0.77)		0.008
TLS density
High vs. Low	0.66(0.44–0.98)	0.039	0.60(0.39–0.93)	0.024	0.29(0.16–0.55)		< 0.001
Multivariable analysis
Smoking status
Ever vs. Never	1.69(1.17–2.45)	0.005	1.42(0.89–2.25)	0.137
Differentiation
G3/G4 vs. G1/G2	1.66(1.10–2.51)	0.016	1.39(0.89–2.15)	0.146	1.64(1.09–2.48)		0.019
TNM stage
II vs. I	1.95(1.18–3.23)	0.010	2.07(1.20–3.59)	0.009	2.20(1.27–3.81)		0.005
III vs. I	3.81(2.40–6.04)	<0.001	5.16(3.11–8.56)	<0.001	3.46(2.16–5.56)		< 0.001
LVI
Yes vs. No	1.78(0.97–3.25)	0.062
TLS density
High vs. Low	0.61(0.41–0.92)	0.017	0.60(0.37–0.95)	0.031	0.32(0.17–0.60)		< 0.001

HR, hazard ratio; CI, confidence interval; G1/G2, well-differentiated or moderately differentiated; G3/G4, poorly differentiated or undifferentiated; IP1, immune-desert phenotype; IP2, immune-excluded phenotype; IP3, inflamed phenotype; VPI, visceral pleural invasion; LVI, lymphovascular invasion.