TROP2 as Patient-Tailoring but Not Prognostic Biomarker for Breast Cancer

Figures & data

Table 1 The Expression Level of TROP2 in Breast Tissues

Characteristic	Cases	TROP2 Expression (%)		Pearson χ2	P-value
		Low	High
Total cases	404
BC tissue	241	142 (58.92)	99 (41.08)	3.993	0.046
Matched adjacent tissue	163	112 (68.71)	51 (31.29)
Total cases	241
TNBC tissue	32	13 (40.62)	19 (59.38)	5.103	0.024
Other BC tissue	209	129 (61.72)	80 (38.28)

Abbreviations: BC, breast cancer; TNBC, triple negative breast cancer.

Figure 1 IHC staining of TROP2 in BC tissues on tissue microarray sections. Positive staining was observed as dark brown color. (A and E) Low expression of TROP2 in BC tissues and matched adjacent tissues, respectively. (C and G) High expression of TROP2 in BC tissues and matched adjacent tissues, respectively. (A), (C), (E) and (G) were scanned by Vectra Polaris Pathology Imaging System at ×10 magnification (bar, 500 μm), (B), (D), (F) and (H) were shown at original × 50 magnification (bar, 100 μm).

Abbreviations: IHC, Immunohistochemistry; BC, breast cancer.

Table 2 Correlation Between the TROP2 Expression Levels and Clinicopathologic Features in BC Patients

Clinicopathologic Parameters	Cases	TROP2 Expression		Pearson χ2	P-value
		Low	High
Total cases	241
Age				2.086	0.149
≤50	88	53	35
>50	153	89	64
ER				5.224	0.022
Negative	64	30	34
Positive	177	112	65
PR				3.336	0.068
Negative	79	40	39
Positive	162	102	60
HER2				0.814	0.367
Negative	75	41	34
Positive	166	101	65
Tumor size (cm)				1.146	0.564
≤2	82	52	30
>2 and ≤5	139	78	61
>5	20	12	8
Ki-67				0.023	0.879
Low	113	66	47
High	128	76	52
Lymph node status				1.399	0.237
N0	155	87	68
N1+N2+N3	86	55	31
TNM stage				5.755	0.056
I	55	35	20
II	140	74	66
III	46	33	13
Morphologic subtypes				1.267	0.737
Ductal carcinoma in situ	20	10	10
Invasive ductal carcinoma	198	119	79
Invasive lobular carcinoma	11	7	4
Mucinous adenocarcinoma	12	6	6

Abbreviations: BC, breast cancer; ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2.

Figure 2 Survival analysis based on TROP2 expression in BC tissues by Kaplan–Meier method and Log rank test. (A) Survival analysis in 241 BC patients collected from Shanghai General Hospital, China. (B) Survival analysis in 181 BC patients from Tang_2018 and Liu_2014 online protein databases (Kaplan–Meier Plotter).

Abbreviation: BC, breast cancer.

Table 3 Summary of the TROP2 Relative Expression Levels, IC₅₀ and I_max Values of Diverse BC Cell Lines

Cell	Subtype	TROP2 Relative Expression	IC50 (nM)		Imax (%)
			MMAE	DS001	MMAE	DS001
MDA-MB-468	TNBC	57098	0.1102	0.3019	67.35	66.65
SK-BR-3	HER2+	48,206	0.0489	0.0245	75.64	74.83
MCF-10A	Fibroadenoma	41,671	0.3391	0.47	82.22	64.33
MCF7	Luminal A	30490	1.592	0.4261	61.63	27.25
HCC1806	TNBC	19182	0.0958	0.2512	74.46	71.31
MDA-MB-231	TNBC	5718	0.3787	145	61.99	59.68
MDA-MB-453	TNBC	1971	0.0715	117.5	65.75	55.64
SUM159	TNBC	7	0.5506	>300	75.42	−26.1

Abbreviations: BC, breast cancer; MMAE, monomethyl auristatin E; IC₅₀, half maximal inhibitory concentration; I_max, maximal inhibition rate.

Figure 3 The expression levels of TROP2 were significantly correlated with the anti-tumor effects of DS001 in diverse BC cell lines. Dose-response curves generated after 96 h treatment with (A) MMAE and (B) DS001. Data were represented as mean ± SD (n = 3). Correlation between the TROP2 expression levels and IC₅₀ values for (C) MMAE and (D) DS001. Correlation between the TROP2 expression levels and the I_max (%) values for (E) MMAE and (F) DS001. Pearson correlation coefficients were shown.

Abbreviations: BC, breast cancer; MMAE, monomethyl auristatin E; IC₅₀, half maximal inhibitory concentration; I_max, maximal inhibition rate.

Figure 4 The expression levels of TROP2 were correlated with the anti-tumor effects of DS001 in PDOs. (A and B) IHC images of BC PDOs with high and low expression levels of TROP2, respectively. Images were captured by an Olympus optical microscope at 400× magnification (bar, 50 μm). (C and D) Dose-response curves of DS001 in PDOs with high and low TROP2 expression levels, respectively. (E) Calculated IC₅₀ and I_max values by nonlinear regression (four-parameter).

Abbreviations: BC, breast cancer; PDO, patient-derived organoid; IHC, Immunohistochemistry; IC₅₀, half maximal inhibitory concentration; I_max, maximal inhibition rate.