Polymorphisms in AURKA and AURKB are associated with the survival of triple-negative breast cancer patients treated with taxane-based adjuvant chemotherapy

Figures & data

Table 1 Information for the SNPs genotyped in this study

SNPs	Position	Location	Alleles	Gene	MAF in CHB
rs10485805	20:56370727	Intron variant	A/G	AURKA	0.302
rs1468056	20:56390932	Intron variant	C/G	AURKA	0.128
rs2236207	20:56392509	utr variant 5 prime	A/G	AURKA	0.093
rs2298016	20:56384240	Intron variant	C/G	AURKA	0.367
rs6099128	20:56390288	Intron variant	G/T	AURKA	0.167
rs8173	20:56369735	utr variant 3 prime	C/G	AURKA	0.395
rs7503353	17:8204661	Downstream variant 500B	G/T	AURKB	0.163
rs11651993	17:8212456	Upstream variant 2 KB	C/T	AURKB	0.105
rs11869914	17:8211831	Upstream variant 2 KB	G/T	AURKB	0.386
rs2289590	17:8207446	Intron variant	A/C	AURKB	0.267
rs3027257	17:8208935	Intron variant	C/T	AURKB	0.267

Abbreviations: CHB, Han Chinese in Beijing; MAF, minor allele frequency; SNP, single-nucleotide polymorphism.

Table 2 Clinicopathological characteristics and survival of TNBC

Variables	Patients (%)	5-year DFS (%)	HR (95% CI)	P	5-year OS (%)	HR (95% CI)	P
Age (years)
≤50	166 (60.8)	68.9	1 (Ref)		87.2	1 (Ref)
>50	107 (39.2)	79.5	0.586 (0.339–1.011)	0.055	86.8	0.876 (0.403–1.901)	0.737
Menopause
Pre	142 (52.0)	72.1	1 (Ref)		90.1	1 (Ref)
Post	131 (48.0)	72.9	1.320 (0.806–2.160)	0.270	83.8	1.271 (0.605–2.673)	0.526
Grade
1–2	70 (25.6)	68.9	1 (Ref)		96.8	1 (Ref)
3	152 (55.7)	76.9	1.101 (0.609–1.992)	0.750	79.5	3.640 (1.071–12.373)	0.039
UK	51 (18.7)	71.9	0.977 (0.469–2.034)	0.950	91.1	2.219 (0.554–8.891)	0.260
Vascular invasion
Negative	255 (93.4)	73.5	1 (Ref)		87.1	1 (Ref)
Positive	18 (6.6)	64.2	1.477 (0.636–3.427)	0.364	82.6	2.108 (0.729–6.097)	0.169
Tumor size
≤2 cm	127 (46.5)	83.5	1 (Ref)		95.6	1 (Ref)
>2 cm	146 (53.5)	63.9	2.376 (1.377–4.098)	0.002	80.3	3.983 (1.514–10.478)	0.005
Lymph node
Negative	162 (59.3)	81.0	1 (Ref)		98.1	1 (Ref)
Positive	111 (40.7)	61.0	3.039 (1.822–5.068)	<0.001	72.1	13.219 (3.990–43.797)	<0.001
TNM
I	84 (30.8)	85.4	1 (Ref)		100.0	1 (Ref)
II	137 (50.2)	75.6	1.814 (0.852–3.860)	0.122	92.9	5.801 (0.742–45.350)	0.094
III	52 (19.0)	45.5	7.272 (3.419–15.468)	<0.001	52.3	36.227 (4.811–272.806)	<0.001

Abbreviations: DFS, disease-free survival; OS, overall survival; Ref, reference; TNBC, triple-negative breast cancer; UK, unknown.

Table 3 AURKA or AURKB genotypes and DFS

Variables	Patients (%)	5-year DFS (%)	Crude		Adjusted
			HR (95% CI)	P	HR (95% CI)	P
AURKB rs11651993
TT	207 (75.8)	76.2	1 (Ref)		1 (Ref)
TC	58 (21.3)	64.0	1.876 (1.087–3.237)	0.024	1.838 (1.064–3.173)	0.029
CC	8 (2.9)	56.3	2.417 (0.745–7.841)	0.142	2.162 (0.652–7.168)	0.208
TT vs TC + CC			1.934 (1.149–3.254)	0.013	1.876 (1.116–3.154)	0.018
TT + TC vs CC			2.045 (0.639–6.543)	0.228	1.868 (0.570–6.127)	0.302
AURKB rs2289590
CC	152 (55.7)	68.1	1 (Ref)		1 (Ref)
CA	105 (38.5)	77.0	0.562 (0.325–0.972)	0.039	0.533 (0.307–0.927)	0.026
AA	16 (5.8)	87.5	0.357 (0.086–1.475)	0.155	0.559 (0.130–2.400)	0.434
CC vs CA + AA			0.531 (0.313–0.902)	0.019	0.536 (0.315–0.912)	0.021
CC + CA vs AA			0.438 (0.107–1.796)	0.252	0.685 (0.161–2.922)	0.609

Abbreviations: DFS, disease-free survival; OS, overall survival; Ref, reference.

Table 4 AURKA or AURKB genotypes and overall survival

Variables	5-year OS (%)	Crude		Adjusted
		HR (95% CI)	P	HR (95% CI)	P
AURKA rs10485805
GG	91.2	1 (Ref)		1 (Ref)
GA	78.9	2.177 (1.024–4.628)	0.043	1.987 (0.912–4.328)	0.084
AA	100.0	–		–
GG vs GA + AA		1.757 (0.830–3.719)	0.141	1.605 (0.746–3.451)	0.226
GG + GA vs AA		0.043 (0.000–19.180)	0.312	–
AURKA rs6099128
TT	88.4	1 (Ref)		1 (Ref)
TG	85.5	1.081 (0.434–2.693)	0.868	1.128 (0.448–2.841)	0.799
GG	45.0	3.248 (0.749–14.091)	0.116	12.889 (2.386–69.627)	0.003
TT vs TG + GG		1.296 (0.570–2.945)	0.536	1.440 (0.627–3.308)	0.391
TT + TG vs GG		0.313 (0.073–1.339)	0.117	12.499 (2.357–66.298)	0.003

Abbreviations: OS, overall survival; Ref, reference.

Figure 1 Kaplan–Meier curve of OS for patients with different AURKA rs6099128 genotypes.

Abbreviation: OS, overall survival.

Figure 2 Kaplan–Meier curve of DFS for patients with different AURKB rs11651993 genotypes.

Abbreviation: DFS, disease-free survival.

Figure 3 Kaplan–Meier curve of DFS for patients with different AURKB rs2289590 genotypes.

Abbreviation: DFS, disease-free survival.

Table 5 Subgroup analysis of polymorphisms and survival

Variants	Subgroup	DFS		OS
		HR (95% CI)	P	HR (95% CI)	P
RS11651993 TT vs TC + CC	Age ≤ 50 years	1.942 (1.046–3.606)	0.036	1.093 (0.358–3.333)	0.876
	Age > 50 years	1.913 (0.738–4.956)	0.182	7.309 (1.817–29.402)	0.005
	Pre-menopausal	1.314 (0.581–2.975)	0.512	2.598 (0.842–8.015)	0.097
	Post-menopausal	2.613 (1.309–5.218)	0.006	1.806 (0.612–5.328)	0.284
	Grade 1–2	1.274 (0.442–3.671)	0.654	0.033 (0.000–4,638.821)	0.572
	Grade 3	1.769 (0.864–3.623)	0.119	2.801 (1.086–7.224)	0.033
	Grade UK	3.480 (1.110–10.914)	0.032	4.420 (0.810–24.130)	0.086
	Tumor size ≤2 cm	1.844 (0.681–4.991)	0.228	1.149 (0.119–11.093)	0.904
	Tumor size >2 cm	1.990 (1.080–3.668)	0.027	2.236 (0.966–5.178)	0.060
	LN negative	3.520 (1.526–8.122)	0.003	2.525 (0.210–30.414)	0.466
	LN positive	1.377 (0.689–2.751)	0.365	2.198 (0.965–5.006)	0.061
RS2289590 CC vs CA + AA	Age ≤ 50 years	0.618 (0.337–1.135)	0.121	1.228 (0.487–3.095)	0.663
	Age > 50 years	0.343 (0.113–1.042)	0.059	1.229 (0.354–4.273)	0.745
	Pre-menopausal	0.377 (0.161–0.884)	0.025	0.978 (0.325–2.944)	0.968
	Post-menopausal	0.676 (0.341–1.343)	0.264	1.405 (0.509–3.878)	0.512
	Grade 1–2	0.528 (0.183–1.521)	0.237	1.730 (0.144–20.752)	0.665
	Grade 3	0.358 (0.162–0.789)	0.011	0.780 (0.306–1.989)	0.602
	Grade UK	1.437 (0.481–4.293)	0.516	5.701 (0.661–49.170)	0.113
	Tumor size ≤2 cm	0.471 (0.168–1.322)	0.153	2.041 (0.340–12.239)	0.435
	Tumor size >2 cm	0.543 (0.293–1.006)	0.052	1.084 (0.478–2.461)	0.847
	LN negative	0.549 (0.226–1.334)	0.185	95.034 (0.007–1280606)	0.348
	LN positive	0.507 (0.262–0.983)	0.044	0.858 (0.388–1.896)	0.705

Abbreviations: DFS, disease-free survival; OS, overall survival; Ref, reference; UK, unknown.