Metastatic colorectal carcinomas with high SATB2 expression are associated with better prognosis and response to chemotherapy: a population-based Scandinavian study

Figures & data

Table 1. Baseline clinicopathological data.

	SATB2
	n, (percent)		p value	q value
	Low 189 (42)	High 261 (58)
Age, mean (range)	69 (24–96)	69 (28–92)	.146*	0.253
Gender
-  Male	88 (47)	134 (51)	.317	0.380
-  Female	101 (53)	127 (49)
Location
-  Right colon	99 (52)	76 (29)
-  Left colon^a	50 (27)	110 (42)	<.001	<0.001
-  Rectum	39 (20)	69 (26)
-  Multiple	1 (1)	6 (2)
Clinical TNM^b stage at diagnosis
-  I-II	33 (18)	39 (15)
-  III	39 (21)	76 (29)	.123	0.246
-  IV	117 (62)	146 (56)
Number of metastatic sites
-  1	76 (40)	113 (43)	.513	0.513
-  ≥2	113 (60)	148 (57)
Metastasis type
-  Synchronous	109 (58)	134 (51)	.184	0.255
-  Metachronous	80 (42)	127 (49)
WHO Performance status
-  0-1	118 (62)	182 (70)	.105	0.246
-  ≥2	71 (38)	79 (30)
Alkaline phosphatase
-  High^c	82 (43)	138 (53)	.191	0.255
-  Normal	77 (41)	99 (38)
-  missing	30 (16)	24 (9)
Tumour differentiation
-  Well-medium diff	122 (65)	219 (84)	<.001	<0.001
-  Low and undifferentiated	62 (33)	34 (13)
-  missing	5 (2)	8 (3)
Chemotherapy for mCRC
-  Given	108 (57)	174 (67)	.039	0.117
-  Not given	81 (43)	87 (33)
BRAF
-  wt	119 (63)	227 (87)	<.001	<0.001
-  mutated	69 (36)	33 (12)
-  missing	1 (1)	1 (1)
KRAS
-  wt	113 (60)	143 (55)	.352	0.384
-  mutated	71 (38)	108 (41)
-  missing	30 (2)	24 (4)

Baseline clinicopathological data of the study cohort according to SATB2 expression. Data are presented as number of patients and percentages of respective group (in parentheses). Chi-square test with contingency coefficient or Mann–Whitney U Test (*) was used for evaluation of statistical significance. The Benjamini-Hochberg FDR adjustment for multiple testing was applied (q-values).

^aLeft colon includes colon from splenic flexure and sigmoid.

^bTNM stages according to AJCC 7^th ed.: Stage I-II = T1-4N0M0, Stage III = T1-4N1-2M0, Stage IV = T1-4N1-2M1.

^cAlkaline phosphatase high was defined according to clinical routine practice at the laboratories in Bergen, Odense and Uppsala.

Figure 1. Kaplan–Meier plot of overall survival (from the date of metastatic diagnosis) in patients having high-SATB2 (red line) versus low-SATB2 expression (blue line). (A) The whole TMA cohort. (B) According to treatment provided. Overall survival of patients receiving chemotherapy was better for those having high SATB2 expression (left panel), while it was less affected by SATB2 expression in patients not receiving chemotherapy (right panel). Log rank test used for the analysis of statistical significance.

Table 2. SATB2 and clinicopathological parameters as prognostic factors for overall survival (univariable Cox regression model) in patients with mCRC.

Covariates	Number of patients	HR	95% CI for HR
			Lower	Upper
SATB2 expression (low vs high)	189/261	1.51	1.24	1.83
Age at diagnosis (>75 vs < =75)	153/297	2.15	1.76	2.64
Gender (female)	228/222	1.03	0.85	1.24
Localization (right vs left)	175/268	1.31	0.08	1.60
Synchronous metastases	243/207	0.88	0.73	1.07
Number of metastatic sites (2 or more vs 1)	261/189	1.44	1.19	1.75
WHO PS (2,3 vs 0,1)	150/300	2.87	2.33	3.53
Alkaline Phosphatase (elevated vs normal)	220/176	1.66	1.35	2.05
Tumour differentiation (poor vs well)	96/341	1.67	1.33	2.11
Loss of CK20	59/391	1.17	0.88	1.55
Loss of CDX2	51/397	2.58	1.91	3.47
BRAF (mut vs wt)	102/364	1.68	1.34	2.10
KRAS (mut vs wt)	179/256	0.99	0.82	1.21

HR: hazard ratio; CI: confidence interval.

Table 3. Multivariable analysis.

Covariates	Number of patients	HR	95.0% CI for HR
			Lower	Upper
SATB2 expression (low vs high)	150/216	1.31	1.02	1.67
Age at diagnosis (>75 vs <=75)	110/256	1.94	1.51	2.50
Localization (right vs left)	140/226	1.05	0.83	1.34
Number of metastatic sites (2 or more vs 1)	207/159	1.30	1.04	1.62
WHO PS (2,3 vs 0,1)	112/254	2.52	1.98	3.22
Alkaline Phosphatase (elevated vs normal)	205/161	2.11	1.68	2.65
Tumour differentiation (poor vs well)	83/283	1.44	1.09	1.90
BRAF (mut vs wt)	82/284	1.55	1.14	2.10
KRAS (mut vs wt)	150/216	1.10	0.87	1.39

HR: hazard ratio; CI: confidence interval.

SATB2 as a prognostic factor for overall survival in multivariable analysis (Cox regression model) in patients with mCRC.

Table 4. OS and PFS in different treatment groups.

		SATB2 low	SATB2 high	p-value
OS	5-FU + Oxaliplatin (165)	16.0	22.0
		(12.8–19.2)	(15.9–28.1)	.066
	5-FU alone (57)	9.0	12.0
		(2.0–16.0)	(7.6–16.4)	.333
	5-FU + Irinotecan (50)	14.0	26.0
		(11.4–16.6)	(21.5–30.5)	<.001
	Irinotecan alone (7)	10.0	18.0
		(7.1–12.9)	(0.0–38.9)	.221
	BSC	3.0	3.0
		(2.0–4.0)	(1.4–4.6)	.046
PFS	5-FU + Oxaliplatin (165)	7.0	8.0
		(5.9–8.1)	(6.9–9.1)	.471
	5-FU alone (57)	3.0	4.0
		(0.0–6.7)	(2.2–5.8)	.723
	5-FU + Irinotecan (50)	5.0	9.0
		(1.5–8.5)	(7.0–11.0)	.124
	Irinotecan alone (6)	2.0	5.3
		(0.0–4.0)*	(3.0–7.7)	.115
	Irinotecan in any combination (59)	4.0	8.0
		(1.3–6.7)	(6.2–9.8)	.019

Data are presented as median OS and PFS in months and as CI (in parentheses), of respective group, except for *, for which mean is shown (due to too few cases). Log-rank test used for the analyses of statistical significance.