Table 2.

Association of intratumoral gene expression with RFS and OS in CLM

		RFS					OS
Genea	n	Median (95% CI)	Uni HR (95% CI)	P a	Multi HR (95% CI)	P b	3-yr rate ± SE	Uni HR (95% CI)	P b	Multi HR (95% CI)	P b
		ACVRL1				0.59		0.11			0.034		0.041
0	13	29.1 (10.3–81.2)	1 (reference)		1 (reference)		0.75 ± 0.13	1 (reference)		1 (reference)
≤ 0.390	12	9.5 (4.1–16.5)	2.86 (1.06–7.73)		2.95 (1.07–8.12)		0.36 ± 0.16	3.37 (0.98–11.56)		2.46 (0.69–8.71)
> 0.390	95	11.7 (9.2–14.4)	1.97 (0.91–4.30)		1.73 (0.78–3.82)		0.71 ± 0.05	1.25 (0.44–3.56)		0.82 (0.27–2.46)
EGFL7				0.052		0.044			0.51		0.88
0	13	29.1 (10.3–81.2)	1 (reference)		1 (reference)		0.75 ± 0.13	1 (reference)		1 (reference)
0.001	63	16.0 (10.1–20.3)	1.58 (0.71–3.51)		1.46 (0.64–3.32)		0.70 ± 0.07	1.30 (0.44–3.81)		0.91 (0.30–2.80)
> 0.001	42	8.4 (5.4–11.7)	3.05 (1.34–6.91)		2.45 (1.06–5.67)		0.62 ± 0.09	1.76 (0.58–5.30)		1.11 (0.34–3.61)
EPHB4				0.043		0.16			0.20		0.66
0	13	29.1 (10.3–81.2)	1 (reference)		1 (reference)		0.75 ± 0.13	1 (reference)		1 (reference)
≤ 0.286	99	13.0 (10.1–16.3)	1.88 (0.87–4.06)		1.75 (0.79–3.88)		0.69 ± 0.05	1.38 (0.49–3.89)		1.00 (0.34–2.93)
> 0.286	12	7.7 (4.5–10.8)	4.67 (1.67–13.06)		2.78 (0.97–8.00)		0.32 ± 0.18	2.89 (0.77–10.90)		1.59 (0.39–6.59)
HIF1A				0.017		0.002			0.27		0.61
0	13	29.1 (10.3–81.2)	1 (reference)		1 (reference)		0.75 ± 0.13	1 (reference)		1 (reference)
≤ 1.725	82	9.5 (6.5–11.1)	2.62 (1.21–5.70)		2.26 (1.01–5.02)		0.62 ± 0.06	1.74 (0.61–4.94)		1.20 (0.40–3.62)
> 1.725	20	91.1+	0.67 (0.23–1.96)		0.60 (0.20–1.82)		0.81 ± 0.10	0.87 (0.22–3.49)		0.71 (0.17–2.91)
VEGFA				0.36		0.063			0.26		0.65
0	13	29.1 (10.3–81.2)	1 (reference)		1 (reference)		0.75 ± 0.13	1 (reference)		1 (reference)
≤ 6.573	65	13.0 (9.2–16.3)	1.96 (0.88–4.33)		1.65 (0.73–3.73)		0.73 ± 0.06	1.28 (0.43–3.74)		0.94 (0.30–2.94)
> 6.573	29	9.5 (4.9–11.1)	2.89 (1.23–6.79)		2.68 (1.11–6.47)		0.53 ± 0.12	2.12 (0.68–6.61)		1.39 (0.40–4.75)
VEGFB				0.001		<.0001			0.013		0.065
0	13	29.1 (10.3–81.2)	1 (reference)		1 (reference)		0.75 ± 0.13	1 (reference)		1 (reference)
≤ 4.135	65	8.3 (5.6–10.3)	3.36 (1.55–7.32)		3.29 (1.45–7.46)		0.57 ± 0.07	2.12 (0.74–6.04)		1.56 (0.50–4.82)
> 4.135	28	91.1+	0.84 (0.33–2.10)		0.71 (0.27–1.87)		0.91 ± 0.06	0.54 (0.14–2.16)		0.44 (0.11–1.83)
VEGFC				0.034		0.025			0.10		0.34
0	13	29.1 (10.3–81.2)	1 (reference)		1 (reference)		0.75 ± 0.13	1 (reference)		1 (reference)
≤ 0.481	98	10.3 (8.3–13.5)	2.34 (1.08–5.07)		2.07 (0.93–4.61)		0.62 ± 0.06	1.65 (0.59–4.64)		1.16 (0.39–3.43)
> 0.481	13	72.7+	0.60 (0.18–2.02)		0.66 (0.19–2.26)		1.00 ± 0.00	0.29 (0.03–2.58)		0.26 (0.03–2.36)
FLT1				0.23		0.27			0.62		1.00
0	13	29.1 (10.3–81.2)	1 (reference)		1 (reference)		0.75 ± 0.13	1 (reference)		1 (reference)
≤ 1.403	101	10.5 (8.3–14.3)	2.16 (0.99–4.70)		1.86 (0.84–4.11)		0.66 ± 0.05	1.50 (0.53–4.23)		1.01 (0.34–2.99)
> 1.403	11	18.5 (10.3–54.4)	1.20 (0.40–3.55)		1.40 (0.46–4.28)		0.72 ± 0.18	0.94 (0.17–5.13)		1.02 (0.18–5.82)
KDR				0.039		0.015			0.27		0.63
0	13	29.1 (10.3–81.2)	1 (reference)		1 (reference)		0.75 ± 0.13	1 (reference)		1 (reference)
≤ 0.691	65	9.5 (5.8–12.8)	2.70 (1.23–5.95)		2.29 (1.02–5.13)		0.58 ± 0.07	1.70 (0.59–4.93)		1.04 (0.34–3.19)
> 0.691	39	17.8 (11.7–91.1)	1.24 (0.53–2.91)		1.16 (0.49–2.79)		0.82 ± 0.07	0.99 (0.31–3.15)		0.72 (0.21–2.40)

^amRNA levels of gene were dichotomized on the optimal cut-off value using the maximal χ² method on RFS. P value for univariable analysis of RFS was adjusted for considering potential multiple cut-off value.

^bP values were based on log-rank test in the univariate analysis and Wald test in the multivariate analysis within Cox regression model. Multivariate Cox regression model was adjusted for age (<65 vs. ≥65 yrs), number of mets (1–2 Mets vs. >2 Mets), timing to metastases (metachronous vs. synchronous), and bilobar (no vs. yes).