Table 4 Univariable and multivariable Cox regression models for cancer-specific and overall survival according to G-cross (G_{tumour:T cell}) proximity function values at 20 µm radius and T cell densities.

From: Prognostic significance of spatial and density analysis of T lymphocytes in colorectal cancer

		Colorectal cancer-specific survival				Overall survival
	No. of cases	No. of events	Univariable HR (95% CI)	Multivariable HR (95% CI)		No. of events	Univariable HR (95% CI)	Multivariable HR (95% CI)
CD3⁺ cell proximity
Tumour center
Q1	246	100	1 (referent)		1 (referent)	152	1 (referent)	1 (referent)
Q2	246	82	0.75 (0.56–1.00)		0.88 (0.65–1.18)	135	0.81 (0.64–1.02)	0.86 (0.68–1.08)
Q3	246	55	0.48 (0.34–0.67)		0.65 (0.46–0.91)	114	0.64 (0.50–0.81)	0.75 (0.58–0.96)
Q4	245	33	0.26 (0.18–0.39)		0.45 (0.30–0.68)	93	0.47 (0.36–0.61)	0.57 (0.43–0.75)
P_trend			<0.0001		<0.0001		<0.0001	<0.0001
Invasive margin
Q1	246	106	1 (referent)		1 (referent)	158	1 (referent)	1 (referent)
Q2	246	91	0.84 (0.63–1.11)		0.93 (0.70–1.24)	137	0.84 (0.67–1.06)	0.88 (0.70–1.11)
Q3	246	45	0.35 (0.25–0.50)		0.61 (0.42–0.88)	94	0.48 (0.37–0.62)	0.66 (0.50–0.86)
Q4	245	28	0.22 (0.15–0.34)		0.35 (0.22–0.55)	105	0.53 (0.42–0.68)	0.62 (0.47–0.81)
P_trend			<0.0001		<0.0001		<0.0001	<0.0001
CD8⁺ cell proximity
Tumour center
Q1	246	95	1 (referent)		1 (referent)	146	1 (referent)	1 (referent)
Q2	246	82	0.85 (0.63–1.15)		1.08 (0.80–1.46)	135	0.91 (0.72–1.14)	1.04 (0.82-1.32)
Q3	246	57	0.54 (0.39–0.75)		0.77 (0.55–1.08)	110	0.65 (0.51–0.84	0.81 (0.63–1.04)
Q4	245	36	0.33 (0.22–0.48)		0.59 (0.39–0.89)	103	0.58 (0.45–0.74)	0.75 (0.57–0.98)
P_trend			<0.0001		0.006		<0.0001	0.012
Invasive margin
Q1	246	110	1 (referent)		1 (referent)	151	1 (referent)	1 (referent)
Q2	246	80	0.70 (0.53–0.94)		0.70 (0.52–0.94)	135	0.85 (0.67–1.07)	0.90 (0.71–1.14)
Q3	246	49	0.38 (0.27–0.53)		0.57 (0.40–0.82)	99	0.54 (0.42–0.70)	0.71 (0.55–0.93)
Q4	245	31	0.24 (0.16–0.35)		0.38 (0.25–0.58)	109	0.59 (0.46–0.75)	0.70 (0.53–0.91)
P_trend			<0.0001		<0.0001		<0.0001	0.003
CD3⁺ cell density
Tumour center
Q1	246	92	1 (referent)		1 (referent)	151	1 (referent)	1 (referent)
Q2	246	85	0.88 (0.66–1.19)		1.17 (0.86–1.59)	135	0.85 (0.67–1.07)	1.14 (0.89–1.45)
Q3	246	54	0.50 (0.36–0.70)		0.71 (0.50–1.00)	105	0.58 (0.45–0.75)	0.79 (0.61–1.02)
Q4	245	39	0.31 (0.25–0.52)		0.52 (0.35–0.76)	103	0.56 (0.43–0.71)	0.67 (0.52–0.87)
P_trend			<0.0001		0.0001		<0.0001	0.0003
Invasive margin
Q1	246	98	1 (referent)		1 (referent)	152	1 (referent)	1 (referent)
Q2	246	81	0.78 (0.58–1.05)		0.92 (0.68–1.24)	127	0.78 (0.61–0.98)	0.89 (0.70–1.13)
Q3	246	55	0.50 (0.36–0.69)		0.66 (0.47–0.93)	114	0.65 (0.51–0.83)	0.75 (0.58–0.96)
Q4	245	36	0.31 (0.21–0.45)		0.48 (0.32–0.71)	101	0.54 (0.42–0.69)	0.61 (0.47–0.80)
P_trend			<0.0001		<0.0001		<0.0001	0.0002
CD8⁺ cell density
Tumour center
Q1	246	90	1 (referent)		1 (referent)	145	1 (referent)	1 (referent)
Q2	246	78	0.84 (0.62–1.13)		0.97 (0.71–1.31)	128	0.85 (0.67–1.08)	0.95 (0.74–1.20)
Q3	246	57	0.59 (0.42–0.82)		0.74 (0.52–1.04)	117	0.73 (0.57–0.93)	0.83 (0.65–1.06)
Q4	245	45	0.44 (0.31–0.63)		0.65 (0.45–0.95)	104	0.61 (0.48–0.79)	0.73 (0.56–0.95)
P_trend			<0.0001		0.010		<0.0001	0.011
Invasive margin
Q1	246	105	1 (referent)		1 (referent)	155	1 (referent)	1 (referent)
Q2	246	62	0.51 (0.37–0.69)		0.73 (0.53–1.02)	112	0.60 (0.47–0.76)	0.76 (0.59–0.97)
Q3	246	61	0.51 (0.37–0.70)		0.65 (0.47–0.90)	114	0.64 (0.50–0.81)	0.72 (0.56–0.93)
Q4	245	42	0.34 (0.24–0.49)		0.53 (0.37–0.78)	113	0.61 (0.48–0.78)	0.72 (0.56–0.94)
P_trend			<0.0001		0.0004		0.0003	0.013

Analyses were done separately for CD3⁺ and CD8⁺ cells in tumour center and in invasive margin by using ordinal quartile categories (Q1–Q4, from low to high).
Multivariable Cox proportional hazards regression models were adjusted for sex, age (<65, 65–75, >75), year of operation (2000–2005, 2006–2010, 2011–2015), tumour location (proximal colon, distal colon, rectum), disease stage (I–II, III, IV), tumour grade (well/moderately differentiated, poorly differentiated), lymphovascular invasion (negative, positive), MMR status (proficient, deficient), BRAF status (wild-type, mutant).
P_trend values were calculated by using the four ordinal categories of G-cross (G_{tumour:T cell}) proximity function values at 20 µm radius and T cell densities as continuous variables in univariable and multivariable Cox proportional hazard regression models.
CI confidence interval, HR hazard ratio.

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Table 4 Univariable and multivariable Cox regression models for cancer-specific and overall survival according to G-cross (G_{tumour:T cell}) proximity function values at 20 µm radius and T cell densities.

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