Distinct prognosis of mRNA expression of the five RecQ DNA-helicase family members – RECQL, BLM, WRN, RECQL4, and RECQL5 – in patients with breast cancer

Figures & data

Figure 1 Survival curves of RECQL mRNA expression in all BCs from the database (Affymetrix ID for RECQL: 212918_at).

Notes: (A) RFS curve; (B) PPS curve; (C) OS curve; (D) DMFS curve.

Abbreviations: BC, breast cancer; RFS, relapse-free survival; PPS, postprogression survival; OS, overall survival; DMFS, distant metastasis-free survival.

Figure 2 Survival curves of BLM mRNA expression in all BCs from the database (Affymetrix ID for BLM: 205733_at).

Notes: (A) DMFS curve; (B) OS curve; (C) RFS curve; (D) PPS curve.

Abbreviations: BC, breast cancer; DMFS, distant metastasis-free survival; OS, overall survival; RFS, relapse-free survival; PPS, postprogression survival.

Figure 3 Survival curves of WRN mRNA expression in all BCs from the database (Affymetrix ID for WRN: 205667_at).

Notes: (A) OS curve; (B) RFS curve; (C) DMFS curve; (D) PPS curve.

Abbreviations: BC, breast cancer; OS, overall survival; RFS, relapse-free survival; DMFS, distant metastasis-free survival; PPS, postprogression survival.

Figure 4 Survival curves of RECQL4 mRNA expression in all breast cancers from the database (Affymetrix ID for RECQL4: 213520_at).

Notes: (A) OS curve; (B) DMFS curve; (C) RFS curve; (D) PPS curve.

Abbreviations: BC, breast cancer; OS, overall survival; DMFS, distant metastasis-free survival; RFS, relapse-free survival; PPS, postprogression survival.

Figure 5 Survival curves of RECQL5 mRNA expression in all BCs from the database (Affymetrix ID for RECQL5: 221686_s_at).

Notes: (A) RFS curve; (B) OS curve; (C) DMFS curve; (D) PPS curve.

Abbreviations: BC, breast cancer; RFS, relapse-free survival; OS, overall survival; DMFS, distant metastasis-free survival; PPS, postprogression survival.

Figure 6 OS curves of RECQL with different intrinsic breast cancer subtypes identified for patients in the database (Affymetrix ID for RECQL: 212918_at).

Notes: (A) Basal-like; (B) luminal A; (C) luminal B; (D) HER2.

Abbreviation: OS, overall survival.

Figure 7 OS curves of RECQL4 with the different intrinsic breast cancer subtypes identified for patients in the database (Affymetrix IDs for RECQL4: 213520_at).

Notes: (A) Luminal A; (B) HER2; (C) Luminal B; (D) Basal-like.

Abbreviation: OS, overall survival.

Figure 8 OS curves of RECQL5 with the different intrinsic breast cancer subtypes identified for patients in the database (Affymetrix ID for RECQL5: 221686_s_at).

Notes: (A) HER2; (B) Luminal A; (C) Luminal B; (D) Basal-like.

Abbreviation: OS, overall survival.

Table 1 Correlation of RecQ-member mRNA expression with OS in different ER statuses of breast cancer patients

RecQ family	Affymetrix ID	ER status	Cases	HR	95% CI	P-value
RECQL	212918_at	Positive	548	1.14	0.80–1.63	0.46
		Negative	251	1.00	0.64–1.57	1.00
BLM	205733_at	Positive	548	1.27	0.89–1.81	0.19
		Negative	251	1.13	0.79–1.61	0.51
WRN	205667_at	Positive	548	1.13	0.79–1.61	0.51
		Negative	251	0.64	0.40–1.02	0.056
RECQL4	213520_at	Positive	548	1.90	1.33–2.74	<0.001
		Negative	251	1.29	0.82–2.03	0.27
RECQL5	221686_s_at	Positive	548	0.97	0.68–1.39	0.88
		Negative	251	0.90	0.57–1.42	0.66

Notes: HR and 95% CI for OS presented as high vs low expression. HR <1 indicates patients with high expression of each RecQ family achieving better OS than low expression.

Abbreviation: OS, overall survival; ER, estrogen receptor.

Table 2 Correlation of RecQ-member mRNA expression with OS in different PR statuses of breast cancer patients

RecQ family	Affymetrix ID	PR status	Cases	HR	95% CI	P-value
RECQL	212918_at	Positive	83	2.90	0.60–14.05	0.17
		Negative	89	1.41	0.56–3.58	0.47
BLM	205733_at	Positive	83	0.66	0.16–2.64	0.55
		Negative	89	1.10	0.44–2.78	0.84
WRN	205667_at	Positive	83	0.81	0.22–3.01	0.75
		Negative	89	0.69	0.27–1.78	0.44
RECQL4	213520_at	Positive	83	4.87	1.01–23.52	0.029
		Negative	89	0.58	0.23–1.51	0.26
RECQL5	221686_s_at	Positive	83	1.10	0.29–4.11	0.89
		Negative	89	3.20	1.14–8.97	0.02

Notes: HR and 95% CI for OS presented as high vs low expression. HR <1 indicates patients with high expression of each RecQ family achieving better OS than low expression.

Abbreviation: OS, overall survival; PR, progesterone receptor.

Table 3 Correlation of RecQ-member mRNA expression with OS in different lymph-node statuses of breast cancer patients

RecQ family	Affymetrix ID	Lymph-node status	Cases	HR	95% CI	P-value
RECQL	212918_at	Positive	313	0.70	0.47–1.03	0.07
		Negative	594	1.26	0.87–1.83	0.22
BLM	205733_at	Positive	313	1.05	0.72–1.55	0.79
		Negative	594	1.08	0.74–1.56	0.70
WRN	205667_at	Positive	313	0.80	0.54–1.18	0.25
		Negative	594	0.92	0.63–1.34	0.65
RECQL4	213520_at	Positive	313	1.30	0.88–1.92	0.18
		Negative	594	1.38	0.95–2.01	0.09
RECQL5	221686_s_at	Positive	313	1.28	0.86–1.89	0.22
		Negative	594	0.68	0.47–0.99	0.043

Notes: HR and 95% CI for OS presented as high vs low expression. HR <1 indicates patients with high expression of each RecQ family achieving better OS than low expression.

Abbreviation: OS, overall survival.

Table 4 Correlation of RecQ-member mRNA expression with OS in different grades of breast cancer patients

RecQ family	Affymetrix ID	Grade	Cases	HR	95% CI	P-value
RECQL	212918_at	I	161	2.02	0.77–5.25	0.14
		II	387	0.79	0.51–1.22	0.29
		III	503	0.99	0.72–1.38	0.97
BLM	205733_at	I	161	1.08	0.43–2.66	0.88
		II	387	1.37	0.89–2.12	0.15
		III	503	0.75	0.54–1.05	0.09
WRN	205667_at	I	161	1.06	0.41–2.74	0.91
		II	387	1.07	0.70–1.64	0.76
		III	503	0.89	0.64–1.24	0.49
RECQL4	213520_at	I	161	0.83	0.33–2.05	0.68
		II	387	1.32	0.86–2.03	0.20
		III	503	1.23	0.88–1.70	0.22
RECQL5	221686_s_at	I	161	0.74	0.30–1.83	0.51
		II	387	1.30	0.85–2.01	0.22
		III	503	0.88	0.63–1.22	0.44

Notes: HR and 95% CI for OS presented as high vs low expression. HR <1 indicates patients with high expression of each RecQ family achieving better OS than low expression.

Abbreviation: OS, overall survival.

Table 5 Correlation of RecQ-member mRNA expression with OS in different TP53 statuses of breast cancer patients

RecQ family	Affymetrix ID	TP53 status	Cases	HR	95% CI	P-value
RECQL	212918_at	Mutant	111	0.33	0.13–0.82	0.013
		Wild type	187	0.74	0.39–1.42	0.37
BLM	205733_at	Mutant	111	1.15	0.53–2.49	0.72
		Wild type	187	1.64	0.84–3.19	0.14
WRN	205667_at	Mutant	111	1.27	0.60–2.71	0.53
		Wild type	187	0.80	0.42–1.53	0.50
RECQL4	213520_at	Mutant	111	1.78	0.82–3.84	0.14
		Wild type	187	1.42	0.74–2.73	0.29
RECQL5	221686_s_at	Mutant	111	1.33	0.59–2.98	0.49
		Wild type	187	1.71	0.88–3.32	0.11

Notes: HR and 95% CI for OS presented as high vs low expression. HR <1 indicates patients with high expression of each RecQ family achieving better OS than low expression.

Abbreviation: OS, overall survival.

Figure 9 Prognostic significances of WRN and RECQL4 protein expression in breast cancer.

Notes: (A) Immunohistochemical analysis of WRN in breast cancer tissue with low staining and high staining; (B) immunochemical analysis of RECQL4 in breast cancer tissue with low staining and high staining; (C) Kaplan–Meier OS analysis of WRN protein expression for patients with breast cancer; (D) Kaplan–Meier OS analysis of RECQL4 protein expression for patients with breast cancer. Each tissue section was observed under microscopy with low magnification of 50× and high magnification of 100×.

Abbreviation: OS, overall survival.

Figure S1 OS curves of BLM with intrinsic different breast cancer subtypes identified for patients in the database (Affymetrix ID for BLM: 205733_at).

Notes: (A) Luminal A, (B) luminal B, (C) HER2, (D) basal-like.

Abbreviation: OS, overall survival.

Figure S2 OS curves of WRN with different intrinsic breast cancer subtypes identified for patients in the database (Affymetrix ID for WRN: 205667_at).

Notes: (A) Luminal A, (B) luminal B, (C) HER2, (D) basal-like.

Abbreviation: OS, overall survival.

Table S1 Clinicopathological characteristics of WRN- and RECQL4-expression cohorts in tumor tissue

	WRN		P-value	RECQL4		P-value
	High (n=67)	Low (n=85)		High (n=55)	Low (n=92)
Age, years			0.931			0.058
>50	35	45		34	42
≤50	32	40		21	50
Laterality			0.614			0.082
Left	28	39		29	35
Right	39	46		26	57
T stage			0.273			0.573
T1	20	16		11	20
T2	41	59		40	60
T3	6	8		4	10
Unknown	0	2		0	2
N stage			0.902			0.414
N0	27	31		19	36
N1	22	26		17	29
N2	14	20		16	18
N3	3	5		1	7
Unknown	1	3		2	2
AJCC stage			0.346			0.893
1	8	5		3	7
2	40	48		31	55
3	18	28		19	27
Unknown	1	4		2	3
ER status			0.205			0.186
Positive	42	60		32	67
Negative	25	23		22	24
Unknown	0	2		1	1
PR status			0.668			0.638
Positive	37	52		31	57
Negative	29	31		23	32
Unknown	1	2		1	3
HER2 status			0.447			0.910
Positive	16	20		13	21
Negative	51	65		42	71

Note: Associations between protein-expression levels of WRN or RECQL4 and clinicopathological features analyzed using Pearson’s χ² test.

Abbreviation: AJCC, American Joint Committee on Cancer.

Data availability

Data on associations of RecQ family-member mRNA expression with prognostic value can be downloaded from the online Kaplan–Meier Plotter breast cancer database (http://kmplot.com/analysis/index.php), and data sets used and analyzed during the current study are available from the corresponding author on reasonable request.