Evaluating the utility of ZNF331 promoter methylation as a prognostic and predictive marker in stage III colon cancer: results from CALGB 89803 (Alliance)

Figures & data

Table 1. Demographics of the study population by ZNF331 promoter methylation status.

	Methylated (N = 267)	Unmethylated (N = 118)	Total (N = 385)	p-value^a
Age				0.01
Median (Years)	63.0	59.0	62.0
Q1, Q3 (Years)	54.0, 70.0	51.0, 67.0	53.0, 69.0
Sex				0.71
Male	148 (55.4%)	63 (53.4%)	211 (54.8%)
Female	119 (44.6%)	55 (46.6%)	174 (45.2%)
Performance Status				0.53
0	203 (76.6%)	93 (79.5%)	296 (77.5%)
1–2	62 (23.4%)	24 (20.5%)	86 (22.5%)
Missing	2	1	3
Treatment Arm				0.34
FU/LV	134 (50.2%)	53 (44.9%)	187 (48.6%)
IFL	133 (49.8%)	65 (55.1%)	198 (51.4%)
Tumor Site				<0.0001
Distal	173 (65.8%)	46 (39.3%)	219 (57.6%)
Proximal	90 (34.2%)	71 (60.7%)	161 (42.4%)
Missing	4	1	5
T-Stage				0.31
T1/T2	21 (8.0%)	15 (12.9%)	36 (9.5%)
T3	222 (84.1%)	93 (80.2%)	315 (82.9%)
T4	21 (8.0%)	8 (6.9%)	29 (7.6%)
Missing	3	2	5
Number of Nodes Sampled				0.28
Median	13.0	12.0	13.0
Q1, Q3	9.0, 19.0	8.0, 17.0	9.0, 18.0
Missing	2	1	3
Number of Positive Nodes				0.89
Median	3.0	3.0	3.0
Q1, Q3	1.0, 5.0	1.0, 5.0	1.0, 5.0
Missing	2	1	3
Extramural Vascular Invasion				0.58
Absent	233 (90.3%)	105 (92.1%)	338 (90.9%)
Present	25 (9.7%)	9 (7.9%)	34 (9.1%)
Missing	9	4	13
Perineural Invasion				0.84
Absent	241 (92.3%)	105 (92.9%)	346 (92.5%)
Present	20 (7.7%)	8 (7.1%)	28 (7.5%)
Missing	6	5	11
Lymphovascular Invasion				0.70
Absent	177 (67.6%)	80 (69.6%)	257 (68.2%)
Present	85 (32.4%)	35 (30.4%)	120 (31.8%)
Missing	5	3	8
Histologic Grade				0.99
Grade 1/2	201 (76.1%)	89 (76.1%)	290 (76.1%)
Grade 3/4	63 (23.9%)	28 (23.9%)	91 (23.9%)
Missing	3	1	4
MMR Status				0.07
pMMR	216 (85.0%)	102 (91.9%)	318 (87.1%)
dMMR	38 (15.0%)	9 (8.1%)	47 (12.9%)
Missing	13	7	20
BRAF^V600E				0.003
Wildtype	207 (81.5%)	103 (93.6%)	310 (85.2%)
Mutant	47 (18.5%)	7 (6.4%)	54 (14.8%)
Missing	13	8	21
KRAS mutation				0.049 [2]
Wildtype	160 (63.0%)	81 (73.6%)	241 (66.2%)
Mutant	94 (37.0%)	29 (26.4%)	123 (33.8%)
Missing	13	8	21
TP53 mutation				0.17
Wildtype	113 (61.1%)	45 (52.3%)	158 (58.3%)
Mutant	72 (38.9%)	41 (47.7%)	113 (41.7%)
Missing	82	32	114
CIMP Status				<0.0001
CIMP^–	184 (69.2%)	113 (97.4%)	297 (77.7%)
CIMP^+	82 (30.8%)	3 (2.6%)	85 (22.3%)
Missing	1	2	3

^ap-values were calculated by χ² test for all categorical variables, and Kruskal-Wallis test for continuous variables (i.e., Age, Number of Nodes Sampled, and Number of Positive Nodes).

Figure 1. Overall survival by ZNF331 promoter methylation status. (a) OS is based on ZNF331 promoter methylation status in the total analysis population (N = 385). There was no significant difference in OS in patients with methylated versus unmethylated ZNF331 colon cancers. (b) Evaluation of ZNF331 promoter methylation status as a prognostic marker of OS.

Figure 2. Disease-free survival by ZNF331 promoter methylation status. (a) DFS OS is based on ZNF331 promoter methylation status in the total analysis population (N = 385). There was no significant difference in DFS in patients with methylated versus unmethylated ZNF331 colon cancers. (b) Evaluation of ZNF331 promoter methylation status as a prognostic marker of DFS.

Figure 3. Overall survival (OS) for patients treated with FU/LV vs IFL based on ZNF331 promoter methylation status. Interaction of ZNF331 promoter methylation status and treatment arm on disease-free survival: (a) unmethylated ZNF331 and (b) methylated ZNF331. There was no observed difference in OS based on a two-way interaction model between treatment arm and ZNF331 promoter methylation status. (c) Evaluation of ZNF331 promoter methylation status as a predictive marker of OS.

Figure 4. Disease-free survival (DFS) for patients treated with FU/LV vs IFL based on ZNF331 promoter methylation status. Interaction of ZNF331 promoter methylation status and treatment arm on disease-free survival: (a) unmethylated ZNF331 and (b) methylated ZNF331. There was no observed difference in DFS based on a two-way interaction model between treatment arm and ZNF331 promoter methylation status. (c) Evaluation of ZNF331 promoter methylation status as a predictive marker of DFS.

Muller MF, Ibrahim AE, Arends MJ. Molecular pathological classification of colorectal cancer. Virchows Arch. 2016;469(2):125–134. doi: 10.1007/s00428-016-1956-3

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Data availability statement

De-identified patient data may be requested from Alliance for Clinical Trials in Oncology via http://[email protected] if data are not publicly available. A formal review process includes verifying the availability of data, conducting a review of any existing agreements that may have implications for the project, and ensuring that any transfer is in compliance with the IRB. The investigator will be required to sign a data release form prior to transfer.