Tables at a glance

Table 1

Table 2

Table 3

Table 4

Table 5

Table 6

Figures at a glance

Comments

Figure 1

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Figure 2

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Figure 3

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Figure 4

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Figure 5

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Figure 6

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Figure 7

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Figure 8

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Figure 9

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Figure 10

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Figure 11

Table 1

subtype	Clinical Diagnostic Index				Relapse rate%
subtype	ER	PR	HER2	Ki67	Relapse rate%
Luminal A	+	+	-	-	30–70
Luminal B	+	+	-	+	10–20
HER2 overexpression	-	-	+	NA	5–15
Basal-like	-	-	-	NA	15–20

Table 1: Four subtypes of breast cancer

Table Note: + indicates that the receptor is present, - indicates that the receptor is not present, and NA (not applicable) indicates that it is not applicable

Table 2

Drug	Formula	Molecular weight (g·mol-1)	Number of Rotatable Keys
Tamoxifen	C26H29NO2	371.524	8/32
Lapatinib	C29H26ClFN4O4S	581.069	11/32
Eribulin	C40H59NO11	729.908	24/32
Afimoxifene	C26H29NO2	387.523	9/32

Table 2: Related properties of small drug molecules

Table 3

Database	Samples	DERNA	Expression	DEmiRNAs	DElncRNAs	DEmRNAs
GSE5764	30（10/20）	336	up	2	10	218
GSE5764	30（10/20）	336	down	0	3	103
GSE7904	62（43/19）	791	up	4	36	366
GSE7904	62（43/19）	791	down	5	31	349
GSE8977	22(7/15)	402	up	0	20	157
GSE8977	22(7/15)	402	down	2	11	212
GSE10810	58(31 /27)	391	up	4	15	287
GSE10810	58(31 /27)	391	down	0	0	85

Table 3: Differentially expressed RNAs for breast cancer

Table 4

Characteristics	Univariate analysis					Multivariate analysis
	Hazard.Ratio	CI95	P.value		Hazard.Ratio		CI95	P.value
Age	1.01	1.01-1.02		0.00010198		1	1-1.01	0.60009222
Cancer_Status	0.29	0.2-0.42		0		0.3	0.17-0.51	1.52E-05
estrogen_receptor	0.94	0.8-1.1		0.45603331
he.positive.lymphnodes	0.99	0.97-1.01		0.22350717
histological_type	1.06	0.98-1.15		0.14003869
lymph_node	0.98	0.98-0.99		2.83E-05		0.99	0.98-1	0.05569107
M	0.25	0.1-0.59		0.00176032		0.38	0.09-1.55	0.17728732
margin_status	1.19	0.98-1.44		0.07976564
N	1.04	0.97-1.13		0.27340616
New_Event	0.37	0.28-0.47		0		0.41	0.28-0.6	3.41E-06
progesterone_receptor	0.96	0.84-1.11		0.62162759
race	0.82	0.7-0.96		0.01335634		1.03	0.84-1.26	0.79408382
RiskScore	5.95	3.78-9.38		0		6.4	3.59-11.39	0
Sex	1.31	0.72-2.37		0.37739826
Stage	1.04	0.95-1.15		0.36816163
T	1	0.91-1.09		0.97460252

Table 4: Univariate and multivariate analyses of risk scores and characteristics

Table Note: Age: patient's age; Cancer_Status: TUMOR FREE, WITH TUMOR; estrogen_receptor: breast cancer estrogen receptor status, divided into positive and negative; he.positive.lymphnodes: positive lymph node count; histological_ type: divided into Infiltrating Lobular Carcinoma and others; lymph_node: lymph node count; M, N, T: TNM stage; margin_status: margin status: divided into Negative, Positive, Close; New_Event: whether cancer occurs again. progesterone_receptor: breast cancer progesterone receptor status, divided into Negative and Positive; race: race divided into WHITE, others; RiskScore: model risk score; Sex: gender; Stage: breast cancer staging.

Table 5

Protein	Structure	Expression	PDB	Method	Resolution
COMP,cartilage oligomeric matrix protein		down	3FBY	x-ray	3.15 Å
PIGR,polymeric immunoglobulin receptor		up	1XED	x-ray	1.9 Å
CXCL10,C-X-C motif chemokine ligand 10		down	1O7Y	x-ray	3.00 Å

Table 5: Related properties of small drug molecules

Table 6

Receptor	Ligand	Number of conformations	Binding energy kcal·mol-1	Interaction
Receptor	Ligand	Number of conformations	Binding energy kcal·mol-1	Ligand Atom	Amino Acid Residue	Bond Length / Å
COMP	Tamoxifen	25/50	-2.02	UNL1:HN	ASP248:OD2	2.9
	Lapatinib	5/50	-1.91	UNL1:HN	GLN364:OE1	2.1
	Eribulin	1/50	-5.64	UNL1:HN2	LEU713:O	2.2
	Afimoxifene	2/50	-3.31	UNL1:HO	ASP507:OD2	2.0
PIGR	Tamoxifen	6/50	-3.75	UNL1:O	ASN16:HD21	2.2
	Lapatinib	3/50	-4.21	UNL1:HN1	GLU14:OE2	2.1
	Eribulin	1/50	-4.49	UNL1:O	GLN81:HE22	2.1
	Afimoxifene	2/50	-3.72	UNL1:HO	SER19:O	6.8
CXCL10	Tamoxifen	4/50	-2.88	UNL1:N	GLU57:OE2	2.9
	Lapatinib	4	/	/	/	/
	Eribulin	2/50	-4.04	UNL1:O	LYS46:HZ2	2.2
	Afimoxifene	1/50	-4.85	UNL1:HO	GLN34:O	2.2

Table 6: Interaction between target protein and drug

FIGURE 1

Figure 1: The volcano plot of mRNA in GEO databases The order is GSE5764, GSE7904, GSE8977 and GSE10810. Green represents RNA down-regulation, red represents RNA up-regulation, and blue represent genes with no difference. The absolute value of log2FC indicate the level of these mRNAs

FIGURE 2

Figure 2: The 12 hub DEmRNAs across four datasets

FIGURE 3

Figure 3: Enrichment analysis of DEmRNA by FunRich. followed by MF, CC, BP and KEGG

FIGURE 4

Figure 4: Enrichment analysis of DEmRNA by DAVID, followed by BPCC, BP and KEGG. Among them, the abscissa is the enrichment factor, and the ordinate is the term of enrichment analysis. The size of the circle represents the number of genes, and the color of the circle is the visualization of the value of -log10(10)

FIGURE 5

Figure 5: Enrichment analysis of common DEmRNAs by DAVID. Yellow represents KEGG, brown represents MF, green represents CC, and blue represents BP

FIGURE 6

Figure 6: PPI network of DEmRNA

FIGURE 7

Figure 7: lncRNA–miRNA–mRNA regulatory network in BC. Among them, the red ellipse is miRNA, the green triangle is lncRNA, and the purple diamond represents the mRNA that binds to the target gene

FIGURE 8

Figure 8: Construction of an mRNA risk model based on ce-RNA regulatory network in. (A) Forest plot of three risk genes LRP1, ZIC1, AXIN2, (B) Survival curves of breast cancer patients in two groups, (C) Time-dependent ROC curve of the risk model, (D) Distribution of survival status of samples with increasing risk scores and model gene expression, (E) Comparison of the abundance of 8 types of immune cells with 2 types of stromal cells under MPCounter algorithm in two groups of breast cancer patients

FIGURE 9

Figure 9: Association of risk score and clinical characteristics. (A) No significant difference was identified in patients with different Cancer status, (B) Survival curve of patients with tumor, (C) Survival curve of patient’s tumor free, (D) No significant difference was identified in patients with different New Event, (E) Survival curves for patients with new event, (F) Survival curves for patients with no new events

FIGURE 10

Figure 10: Construction and calibration of nomogram. (A) nomogram integrating risk score and clinical features, (B) calibration of the nomogram at 3 and 5 years, (C) Nomogram Survival Curve, (D) Nomogram ROC Analysis

FIGURE 11

Figure 11: Schematic diagram of the docking of target protein and drug molecule, followed by COMP, PIGR and CXCL10