Associations of two-pore domain potassium channels and triple negative breast cancer subtype in The Cancer Genome Atlas: systematic evaluation of gene expression and methylation

Dookeran, Keith A.; Zhang, Wei; Stayner, Leslie; Argos, Maria

doi:10.1186/s13104-017-2777-4

Table 3 Annotation and expression correlation for select K2p methylation loci associated with triple negative subtype

From: Associations of two-pore domain potassium channels and triple negative breast cancer subtype in The Cancer Genome Atlas: systematic evaluation of gene expression and methylation

Gene	GLM Models^a		Annotation^b	Luminal A^c			Combined triple negative^c
CpG loci	Beta	p-value	Annotation^b	N	Rho	p-value	N	Rho	p-value
KCNK1
cg17851113	0.188	1.45E−12		339	0.487	1.31E−21	103	0.301	2.02E−03
cg23054119	−0.140	3.40E−06		338	0.498	1.37E−22	103	−0.114	2.53E−01
KCNK2
cg04923840	−0.219	2.00E−25	Body	339	0.227	2.52E−05	103	−0.253	9.81E−03
cg06873024	−0.183	1.64E−21	Between CENPF/KCNK2	339	0.124	2.21E−02	103	0.241	1.43E−02
cg24464500	−0.206	9.81E−20	Body	337	0.280	1.70E−07	103	−0.048	6.33E−01
cg13916421	0.085	1.53E−11	Body	339	0.061	2.60E−01	103	−0.211	3.22E−02
cg00848374	0.129	2.35E−07	1stExon; 5′UTR	338	0.202	1.83E−04	103	−0.079	4.27E−01
KCNK3
cg20491914	−0.170	2.97E−11	TSS1500	339	−0.297	2.46E−08	103	−0.164	9.82E−02
cg11273176	−0.128	1.60E−10	Body	339	−0.388	1.23E−13	103	−0.408	1.88E−05
cg06854842	−0.090	2.20E−09	Body	339	−0.360	7.91E−12	103	−0.451	1.78E−06
cg05616379	0.078	1.50E−06	Body	339	−0.221	3.97E−05	103	−0.452	1.64E−06
KCNK4
cg01708924	−0.185	2.87E−31	3′UTR PRDX5	339	−0.221	3.92E−05	103	0.017	8.68E−01
cg10718809	−0.148	2.81E−23	PRDX5: body	339	−0.224	3.04E−05	103	−0.026	7.98E−01
cg10155572	−0.037	1.92E−07	ESRRA: body	339	−0.239	8.75E−06	103	−0.001	9.92E−01
KCNK5
cg05255811	−0.373	9.32E−70	Body	339	−0.369	2.40E−12	103	−0.674	5.95E−15
cg18705155	−0.226	2.71E−26	Body	339	−0.120	2.78E−02	103	−0.605	1.33E−11
cg09130674	−0.224	1.52E−25	Body	339	−0.197	2.65E−04	103	−0.711	3.91E−17
cg21388745	−0.119	1.81E−23	Body	339	−0.203	1.68E−04	103	−0.701	1.59E−16
cg00859574	−0.129	4.14E−08	Body	339	−0.160	3.04E−03	103	−0.430	5.90E−06
cg02128567	−0.113	3.53E−07	1stExon; 5′UTR	339	−0.253	2.35E−06	103	−0.345	3.62E−04
KCNK6
cg13521973	0.039	6.36E−07	Body	339	−0.244	5.62E−06	103	−0.193	5.07E−02
cg08216899	−0.025	5.10E−06	3′UTR	339	0.110	4.25E−02	103	0.217	2.75E−02
KCNK7
cg10142520	−0.210	3.27E−22	EHBP1L1 body	339	−0.215	6.77E−05	103	0.014	8.90E−01
cg17290213	−0.126	1.09E−17	EHBP1L1 body	339	−0.223	3.57E−05	103	0.092	3.55E−01
cg03416228	−0.092	6.06E−15	Between EHBP1L1/KCNK7	339	−0.225	2.91E−05	103	−0.171	8.44E−02
cg12758867	−0.072	2.02E−14	EHBP1L1 body	339	−0.223	3.49E−05	103	0.095	3.38E−01
cg13179915	−0.067	3.13E−11	1stExon	339	−0.205	1.39E−04	103	−0.305	1.75E−03
cg05436845	−0.036	6.28E−06	MAP3K11: body	339	−0.223	3.34E−05	103	0.045	6.51E−01
cg17918700	−0.030	1.55E−05	TSS200	339	−0.230	1.84E−05	103	−0.277	4.55E−03
KCNK9
cg21415530	−0.332	1.14E−56	TSS1500	339	−0.159	3.32E−03	103	−0.383	6.39E−05
cg12175729	−0.273	6.23E−22	TSS1500	339	−0.056	3.02E−01	103	−0.215	2.88E−02
cg20761810	0.155	1.67E−16	Between KCNK9/TRAPPC9	339	0.238	9.24E−06	103	−0.119	2.30E−01
cg05988964	0.183	2.15E−11	3′UTR	339	0.208	1.16E−04	103	0.197	4.56E−02
cg17336929	−0.110	9.79E−10	Between KCNK9/TRAPPC9	339	0.055	3.13E−01	103	−0.248	1.17E−02
cg25900813	−0.106	4.38E−08	Between KCNK9/TRAPPC9	339	0.069	2.07E−01	103	−0.236	1.62E−02
cg24020826	0.102	7.26E−08	3′UTR	339	0.176	1.12E−03	103	0.204	3.84E−02
cg18195416	0.125	6.90E−06	Between COL22A1/KCNK9	339	0.206	1.29E−04	103	0.237	1.60E−02
cg03919980	−0.066	2.96E−05	Between KCNK9/TRAPPC9	339	0.114	3.59E−02	103	−0.222	2.43E−02
KCNK10
cg09945147	0.219	3.03E−33	Between GPR65/KCNK10	339	0.241	7.35E−06	103	0.312	1.32E−03
cg01733928	0.153	4.71E−29	Between GPR65/KCNK10	339	0.250	3.17E−06	103	0.282	3.97E−03
cg08069902	0.190	9.47E−26	Body	339	0.088	1.07E−01	103	0.231	1.90E−02
cg02222791	0.225	1.04E−23	Between GPR65/KCNK10	339	0.238	9.06E−06	103	0.267	6.42E−03
cg18078958	0.219	2.22E−20	Between GPR65/KCNK10	339	0.181	8.11E−04	103	0.290	2.94E−03
cg10172979	0.123	1.23E−14	Between GPR65/KCNK10	339	0.167	2.01E−03	103	0.286	3.40E−03
cg24740404	0.167	1.05E−13	Between GPR65/KCNK10	339	0.166	2.12E−03	103	0.211	3.21E−02
cg15347348	0.134	2.77E−13	Body; TSS1500	339	0.118	2.99E−02	103	0.313	1.27E−03
cg19453093	0.081	3.20E−12	Body	339	0.205	1.46E−04	103	0.375	9.54E−05
cg19476426	0.145	2.58E−11	Between GPR65/KCNK10	339	0.172	1.44E−03	103	0.212	3.16E−02
cg15493607	0.167	4.53E−11	Body; TSS1500	339	0.197	2.64E−04	103	0.313	1.29E−03
cg17671157	−0.105	6.87E−10	1stExon; 5′UTR	337	−0.068	2.10E−01	103	0.229	1.97E−02
cg18525616	0.144	8.98E−10	Between GPR65/KCNK10	339	0.156	4.04E−03	103	0.270	5.81E−03
cg00927624	0.143	3.91E−09	Between KCNK10/SPATA7	339	0.249	3.43E−06	103	0.318	1.08E−03
cg23291854	−0.107	4.26E−08	1stExon; 5′UTR	339	−0.040	4.65E−01	103	0.282	3.85E−03
cg22521269	−0.093	1.35E−06	TSS200	339	−0.116	3.35E−02	103	0.215	2.89E−02
cg02883668	0.079	2.03E−05	Body	339	0.177	1.07E−03	103	0.262	7.40E−03
cg23381267	0.097	6.14E−05	Body	339	0.154	4.44E−03	103	0.227	2.11E−02
KCNK12
cg00981060	0.183	1.55E−20	Between MSH2/KCNK12	339	0.073	1.79E−01	103	0.223	2.38E−02
cg27138584	−0.059	4.47E−05	Body	339	0.003	9.63E−01	103	0.258	8.46E−03
cg00783525	0.054	7.26E−05	Body	339	0.113	3.70E−02	103	0.335	5.39E−04
KCNK13
cg21191365	−0.209	2.20E−20	Body	339	−0.026	6.39E−01	103	0.201	4.17E−02
cg00364611	−0.118	1.32E−11	1stExon	339	−0.170	1.66E−03	103	0.275	4.87E−03
cg25225073	−0.100	4.05E−07	Body	339	0.073	1.80E−01	103	0.303	1.88E−03
KCNK15
cg13598409	0.210	1.39E−56	TSS1500	339	−0.251	2.87E−06	103	0.093	3.50E−01
cg04966972	0.164	7.67E−45	TSS1500	339	−0.298	2.14E−08	103	0.078	4.35E−01
cg11681959	0.109	5.52E−28	TSS200	339	−0.278	2.01E−07	103	−0.053	5.98E−01
cg25301532	−0.113	6.12E−09	Body	339	0.253	2.35E−06	103	0.290	2.99E−03
cg09357268	−0.048	4.75E−08	Body	339	0.195	2.96E−04	103	0.225	2.24E−02
KCNK16
cg05897803	0.114	3.86E−11	TSS200	339	−0.342	1.04E−10	103	0.009	9.28E−01
cg07970874	0.087	2.82E−06	TSS200	339	−0.269	4.73E−07	103	0.019	8.47E−01
KCNK17
cg13855924	−0.142	2.45E−12	Body	339	−0.209	1.09E−04	103	−0.105	2.93E−01
cg04755571	−0.131	5.17E−10	TSS200	339	−0.241	7.29E−06	103	−0.262	7.62E−03
cg06347083	−0.124	5.92E−10	TSS200	339	−0.215	6.61E−05	103	−0.216	2.82E−02
cg10712551	−0.122	1.58E−07	Body	339	−0.175	1.19E−03	103	−0.239	1.49E−02
cg03252829	−0.105	1.61E−05	1stExon; 5′UTR	339	−0.284	1.04E−07	103	−0.200	4.28E−02
cg08315770	−0.103	6.55E−05	1stExon	339	−0.205	1.48E−04	103	−0.084	4.02E−01

mRNA expression z-scores (RNA Seq V2 RSEM)
Spearman’s Rho values of <0.2 or >0.2 were considered evidence of correlation if also associated with p-values <0.05 (these values are in italics)
K2p 2-pore domain K+ channel genes, glm generalized linear model
^aAge and race adjusted associations of individual methylated CpG loci and combined triple negative vs. luminal A subtype were ranked according to p-value (smallest first) and all significant loci were selected for further evaluation (Bonferroni adjusted threshold for methylation analyses = p < 8.22 × 10(−8))
^bAnnotation data obtained from Illumina for Human Methylation 450K chip array (http://support.illumina.com/array/array_kits/infinium_humanmethylation450_beadchip_kit/downloads.html)
^cFunctional correlation between methylation and expression was then examined using Spearman’s correlation and results are presented stratified by subtype

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ISSN: 1756-0500

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