KIF20A is a Prognostic Marker for Female Patients with Estrogen Receptor-Positive Breast Cancer and Receiving Tamoxifen as Adjuvant Endocrine Therapy

Figures & data

Figure 1 The flowchart illustrating the main steps of our study.

Figure 2 Kaplan-Meier curves illustrating the RFS (A), DMFS (B), and OS (C) of ER-positive BC patients receiving TAM therapy, stratified by KIF20A expression levels using the Kaplan-Meier Plotter (P < 0.001, P < 0.001, and P = 0.008, respectively, log rank test).

Abbreviations: RFS, relapse-free survival; DMFS, distant metastasis-free survival; OS, overall survival; ER, estrogen receptor; BC, breast cancer; TAM, tamoxifen.

Figure 3 Predictive value of KIF20A in assessing the treatment outcome of TAM in ER-positive BC patients, evaluated using the ROC Plotter. (A) The comparison of KIF20A gene expression between patients with ER-positive BC who responded and did not respond to TAM therapy (P < 0.001, Mann–Whitney test). (B) The ROC curve depicting the predictive value of KIF20A expression for TAM treatment outcome in patients with ER-positive BC receiving TAM therapy (AUC = 0.63, P < 0.001).

Abbreviations: TAM, tamoxifen; ER, estrogen receptor; BC, breast cancer; ROC, receiver operating characteristic; AUC, area under curve.

Table 1 Relationship Between KIF20A Expression and Clinicopathological Features in Patients with ER-Positive BC

Variables	High KIF20A Expression (%)	Low KIF20A Expression (%)	P value
Age group			0.822
≤35	10 (9.9)	12 (11.8)
>35	91 (90.1)	90 (88.2)
Tumor size			0.206
≤2cm	50 (49.5)	60 (58.8)
>2cm	51 (50.5)	42 (41.2)
LN metastasis			0.105
≤3 LNs	78 (77.2)	88 (86.3)
>3 LNs	23 (22.8)	14 (13.7)
TNM stage			0.074
I_II	77 (76.2)	88 (86.3)
III	24 (23.8)	14 (13.7)
HER2 status			0.111
Negative	79 (78.2)	70 (68.6)
Positive	19 (18.8)	31 (30.4)
Indeterminate	3 (3.0)	1 (1.0)
Ki67 level			0.123
Low	45 (44.6)	57 (55.9)
High	56 (55.4)	45 (44.1)
Histologic grade			0.551
I–II	66 (65.3)	71 (69.6)
III	35 (34.7)	31 (30.4)
Lymphovascular invasion			0.668
Absent	59 (58.4)	63 (61.8)
Present	42 (41.6)	39 (38.2)
Chemotherapy			0.460
No	10 (9.9)	7 (6.9)
Yes	91 (90.1)	95 (93.1)
Radiotherapy			0.160
No	42 (41.6)	53 (52.0)
Yes	59 (58.4)	49 (48.0)
Disease status			0.001*
Disease-free	56 (55.4)	80 (78.4)
Recurrence/metastasis	45 (44.6)	22 (21.6)
Survival status			0.002*
Alive	73 (72.3)	91 (89.2)
Deceased	28 (27.7)	11 (10.8)

Note: *Statistically significant difference.

Abbreviations: ER, estrogen receptor; BC, breast cancer; HER2, human epidermal growth factor receptor 2; LN, lymph node.

Figure 4 IHC analysis of KIF20A expression in tumor tissues of ER-positive BC patients. (A) Representative image showing low expression level of KIF20A (×200). (B) Representative image showing high expression level of KIF20A (×200).

Abbreviations: IHC, immunohistochemistry; ER, estrogen receptor; BC, breast cancer.

Figure 5 The Kaplan-Meier curve depicting the DFS of patients, stratified by KIF20A expression levels (P = 0.001, log rank test).

Abbreviation: DFS, disease-free survival.

Figure 6 The Kaplan-Meier curve depicting the OS of patients, stratified by KIF20A expression levels (P = 0.002, log rank test).

Abbreviation: OS, overall survival.

Table 2 Univariate and Multivariate Cox Analysis Results of Clinicopathological Variables and Expression Levels of KIF20A for DFS of ER-Positive BC Patients with TAM Therapy

Variables	Univariate		Multivariate
	HR (95% CI)	P value	HR (95% CI)	P value
Age groups		0.293
≤ 35	Reference
> 35	0.686 (0.340–1.385)
HER2 status^a		0.406
Negative	Reference
Positive	0.772 (0.419–1.421)
Ki67 level		0.115
Low	Reference
High	1.476 (0.909–2.396)
Histologic grades		0.974
I_II	Reference
III	1.008 (0.606–1.679)
Lymphovascular invasion		0.018*		0.041*
Absent	Reference		Reference
Present	1.784 (1.104–2.883)		1.666 (1.021–2.719)
Tumor size		0.013*		0.068
≤ 2cm	Reference		Reference
> 2cm	1.847 (1.136–3.002)		1.599 (0.965–2.649)
LN metastasis		0.014*		0.278
≤ 3 LNs	Reference		Reference
> 3 LNs	1.968 (1.146–3.381)		1.371 (0.776–2.422)
Chemotherapy		0.778
No	Reference
Yes	1.140 (0.458–2.836)
Radiotherapy		0.529
No	Reference
Yes	1.168 (0.720–1.895)
KIF20A expression		0.001*		0.001*
Low	Reference		Reference
High	2.347 (1.408–3.912)		2.323 (1.387–3.890)

Notes: ^aThere were four patients with indeterminate HER2 status and thus were excluded from the analysis. *Statistically significant difference.

Abbreviations: DFS, disease-free survival; ER, estrogen receptor; BC, breast cancer; TAM, tamoxifen; HER2, human epidermal growth factor receptor 2; LN, lymph node; HR, hazard ratio; CI, confidence interval.

Table 3 Univariate and Multivariate Cox Analysis Results of Clinicopathological Variables and Expression Levels of KIF20A for OS of ER-Positive BC Patients with TAM Therapy

Variables	Univariate		Multivariate
	HR (95% CI)	P value	HR (95% CI)	P value
Age groups		0.211
≤ 35	Reference
> 35	0.573 (0.240–1.370)
HER2 status^a		0.979
Negative	Reference
Positive	0.990 (0.468–2.094)
Ki67 level		0.331
Low	Reference
High	1.368 (0.727–2.573)
Histologic grades		0.691
I_II	Reference
III	1.142 (0.593–2.199)
Lymphovascular invasion		0.008*		0.042*
Absent	Reference		Reference
Present	2.411 (1.263–4.601)		1.992 (1.027–3.865)
Tumor size		0.019*		0.192
≤ 2cm	Reference		Reference
> 2cm	2.189 (1.137–4.214)		1.573 (0.797–3.103)
LN metastasis		0.001*		0.035*
≤ 3 LNs	Reference		Reference
> 3 LNs	3.002 (1.574–5.726)		2.069 (1.052–4.067)
Chemotherapy		0.927
No	Reference
Yes	1.057 (0.325–3.434)
Radiotherapy		0.404
No	Reference
Yes	1.317 (0.690–2.512)
KIF20A expression		0.003*		0.008*
Low	Reference		Reference
High	2.841 (1.413–5.713)		2.604 (1.289–5.260)

Notes: ^aThere were four patients with indeterminate HER2 status and thus were excluded from the analysis. *Statistically significant difference.

Abbreviations: OS, overall survival; ER, estrogen receptor; BC, breast cancer; TAM, tamoxifen; HER2, human epidermal growth factor receptor 2; LN, lymph node; HR, hazard ratio; CI, confidence interval.