Clinical assessment and identification of immuno-oncology markers concerning the 19-gene based risk classifier in stage IV colorectal cancer

Table 1 Association between differential regulation of 19-gene-based risk classifier genes and clinicopathological factors in 60 patients with stage IV colorectal cancer

Variables (No. of patients)	Percentage of tumors with a log22-ΔΔCT value > 1 compared with matched normal tissue (P value)
	GADD45B1	S1PR3	CDKN2B	EGR2	CTGF	SERPINE1	RGS16	RHOU	TIMP1	PHLDA1	IL36RN	SLAMF7	E2F7	DTL	CFB	CDK1	CXCL1	CXCL3	CKS2	TREM1
Mean ± SEM of 2ΔΔCT	0.78 ± 0.74	1.45 ± 4.23	1.64 ± 6.03	3.24 ± 10.88	1.23 ± 1.66	8.19 ± 22.49	10.39 ± 35.49	1.01 ± 1.59	2.90 ± 2.79	5.49 ± 14.95	4.40 ± 15.22	1.17 ± 5.10	9.84 ± 34.23	2.46 ± 4.68	3.29 ± 5.62	2.94 ± 6.51	22.76 ± 75.79	30.55 ± 76.03	2.65 ± 4.14	14.14 ± 71.65
Sex	25.9/24.2	25.9/27.3	22.2/15.2	33.3/39.4	37.0/36.4	74.1/81.8	81.5/69.7	33.3/24.2	74.1/75.8	63.0/66.7	33.3/42.4	3.7/18.2	85.2/84.8	44.4/60.6	70.4/69.7	51.9/60.6	92.6/78.8	96.3/84.8	55.6/75.8	29.6/42.4
Female/male (27/33)	0.56	0.57	0.35	0.42	0.58	0.34	0.23	0.31	0.56	0.49	0.33	0.89	0.63	0.16	0.59	0.34	0.13	0.15	0.08	0.23
Age	23.2/50.0	26.8/25.0	17.9/25.0	37.5/25.0	35.7/50.0	76.8/100	75.0/75.0	28.6/25.0	73.2/100	64.3/75.0	39.3/25.0	10.7/25.0	83.9/100	55.4/25.0	71.4/50.0	58.9/25.0	83.9/100	89.3/100	66.1/75.0	35.7/50.0
≤ 75 vs > 75 (56/4)	0.26	0.71	0.57	0.53	0.47	0.37	0.69	0.68	0.31	0.56	0.5	0.4	0.51	0.26	0.35	0.21	0.51	0.65	0.59	0.47
Comorbidity	20.0/32.0	31.4/20.0	20.0/16.0	42.9/28.0	37.1/36.0	74.3/84.0	80.0/.68.0	34.3/20.0	68.6/84.0	62.9/68.0	45.7/28.0	8.6/16.0	80.0/92.0	60.0/44.0	71.4/68.0	68.6/40.0	82.9/88.0	88.6/92.0	68.6/64.0	37.1/36.0
No/Yes (35/25)	0.22	0.25	0.48	0.18	0.57	0.28	0.22	0.18	0.14	0.45	0.13	0.31	0.18	0.17	0.5	0.03	0.43	0.51	0.46	0.57
Family history	24.0/30.0	28.0/20.0	18.0/20.0	38.0/30.0	36.0/40.0	78.0/80.0	72.0/90.0	28.0/30.0	74.0/80.0	64.0/70.0	42.0/20.0	12.0/10.0	88.0/70.0	56.0/40.0	70.0/70.0	60.0/40.0	88.0/70.0	94.0/70.0	72.0/40.0	36.0/40.0
No/Yes (50/10)	0.48	0.46	0.59	0.46	0.54	0.63	0.22	0.59	0.52	0.51	0.17	0.67	0.16	0.28	0.63	0.21	0.16	0.05	0.06	0.54
Synchronous Lm	33.3/21.4	33.3/23.8	22.2/16.7	33.3/38.1	33.3/38.1	72.2/81.0	83.3/71.4	44.4/21.4	77.8/73.8	66.7/64.3	44.4/35.7	22.2/7.1	72.2/90.5	55.6/52.4	83.3/64.3	72.2/50.0	100/78.6	100/85.7	83.3/59.5	38.9/35.7
No/Yes (18/42)	0.25	0.32	0.43	0.48	0.48	0.33	0.26	0.07	0.51	0.55	0.36	0.11	0.08	0.52	0.12	0.09	0.03	0.1	0.06	0.52
Synchronous Pm	28.9/13.3	26.7/26.7	17.8/20.0	37.8/33.3	35.6/40.0	77.8/80.0	77.8/66.7	31.1/20.0	77.8/66.7	66.7/60.0	40.0/33.3	13.3/6.7	86.7/80.0	57.8/40.0	71.1/66.7	62.2/40.0	88.9/73.3	91.1/86.7	66.7/66.7	40.0/26.7
No/Yes (45/15)	0.2	0.64	0.56	0.51	0.49	0.58	0.3	0.32	0.3	0.43	0.44	0.43	0.4	0.18	0.49	0.11	0.15	0.47	0.62	0.27
AJCC stage	0/25.9	0/27.6	0/11	0/37.9	50/36.2	50/79.3	100/74.1	50/27.6	0/77.6	50/65.5	50/37.9	0/12.1	100/84.5	100/51.7	100/69.0	100/55.2	100/84.5	100/89.7	100/65.5	0/37.9
III/IV (2/58)	0.56	0.53	0.66	0.4	0.6	0.39	0.56	0.49	0.06	0.58	0.62	0.78	0.72	0.28	0.49	0.32	0.72	0.81	0.44	0.4
LVI	10.0/32.5	20.0/30.0	15.0/20.0	25.0/42.5	25.0/42.5	65.0/85.0	65.0/80.0	30.0/27.5	75.0/75.0	45.0/75.0	25.0/45.0	0/17.5	70.0/92.5	35.0/62.5	60.0/75.0	45.0/62.5	75.0/90.0	85.0/92.5	55.0/72.5	30.0/40.0
No/Yes (20/40)	0.05	0.31	0.47	0.15	0.15	0.08	0.17	0.53	0.63	0.02	0.11	0.05	0.03	0.04	0.18	0.16	0.13	0.31	0.14	0.32
PNI	12.0/34.3	32.0/22.9	16.0/20.0	40.0/34.3	32.0/40.0	76.0/80.0	60.0/85.7	36.0/22.9	72.0/77.1	56.0/71.4	40.0/37.1	8.0/14.3	76.0/91.4	52.0/54.3	68.0/71.4	56.0/57.1	76.0/91.4	84.0/94.3	64.0/68.6	24.0/45.7
No/Yes (25/35)	0.04	0.31	0.48	0.43	0.36	0.47	0.02	0.2	0.44	0.17	0.52	0.37	0.1	0.53	0.5	0.57	0.1	0.19	0.46	0.07
CRM involvement	22.4/36.4	26.5/27.3	18.4/18.2	34.7/45.5	38.8/27.3	79.6/72.7	73.5/81.8	30.6/18.2	73.5/81.8	63.3/72.7	36.7/45.5	6.1/36.4	83.7/90.9	51.0/63.6	69.4/72.7	53.1/72.7	85.7/81.8	89.8/90.9	61.2/90.9	30.6/63.6
No/Yes (49/11)	0.27	0.61	0.68	0.37	0.36	0.44	0.44	0.34	0.44	0.41	0.42	0.02	0.47	0.34	0.57	0.2	0.52	0.7	0.05	0.04

¹GADD45B, control gene. Rt: Right; Lt: Left; Re: Rectum; Lm: Hepatic metastasis; Pm: Pulmonary metastasis; AJCC: American Joint Committee on Cancer; LVI: Lymphovascular invasion; PNI: Perineural invasion; CRM: Circumferential resection margin; IHC: Immunohistochemistry.

Table 2 Multivariate analyses of prognostic factors associated with progression-free survival using Cox-regression

	P value	Hazard ratio	CI lower	CI upper
N-category	0.02	0.569	0.349	0.927
LVI	0.004	2.559	1.347	4.862
PNI	0.538	0.837	0.476	1.473
CRM	0.004	2.931	1.398	6.143
Bormann type	0.3	0.731	0.402	1.327
SLAMF7	0.003	0.206	0.072	0.589
CKS2	0.018	0.484	0.266	0.883
TREM1	0.017	0.471	0.254	0.875

CI: Confidence interval; CKS-2: Cyclin-dependent kinases regulatory subunit 2; CRM: Circumferential resection margin; LVI: Lymphovascular invasion; PNI: Perineural invasion; SLAMF7: Signaling lymphocytic activation molecule family, member 7; TREM1: Triggering receptor expressed on myeloid cells 1.