Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: TOP2A

Gene summary for TOP2A

Gene summary.

Gene information	Species	Human
	Gene symbol	TOP2A
	Gene ID	7153
	Gene name	DNA topoisomerase II alpha
	Gene Alias	TOP2
	Cytomap	17q21.2
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P11388

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
7153	TOP2A	GSM4909282	Human	Breast	IDC	7.47e-18	4.64e-01	-0.0288
7153	TOP2A	GSM4909285	Human	Breast	IDC	3.86e-02	1.28e-01	0.21
7153	TOP2A	GSM4909287	Human	Breast	IDC	9.31e-06	3.63e-01	0.2057
7153	TOP2A	GSM4909318	Human	Breast	IDC	2.26e-04	7.14e-01	0.2031
7153	TOP2A	GSM4909319	Human	Breast	IDC	2.41e-03	1.87e-01	0.1563
7153	TOP2A	M1	Human	Breast	IDC	3.07e-03	3.15e-01	0.1577
7153	TOP2A	M2	Human	Breast	IDC	7.33e-05	6.31e-01	0.21
7153	TOP2A	NCCBC14	Human	Breast	DCIS	6.68e-10	6.40e-01	0.2021
7153	TOP2A	P1	Human	Breast	IDC	2.65e-04	4.04e-01	0.1527
7153	TOP2A	HTA11_696_2000001011	Human	Colorectum	AD	9.56e-07	3.38e-01	-0.1464
7153	TOP2A	HTA11_1391_2000001011	Human	Colorectum	AD	2.48e-04	4.93e-01	-0.059
7153	TOP2A	HTA11_99999970781_79442	Human	Colorectum	MSS	4.46e-07	1.99e-01	0.294
7153	TOP2A	A002-C-021	Human	Colorectum	FAP	8.13e-03	1.02e-01	0.1171
7153	TOP2A	LZE2T	Human	Esophagus	ESCC	1.86e-04	1.20e+00	0.082
7153	TOP2A	LZE21T	Human	Esophagus	ESCC	1.61e-04	6.55e-01	0.0655
7153	TOP2A	LZE6T	Human	Esophagus	ESCC	6.79e-07	4.96e-01	0.0845
7153	TOP2A	P2T-E	Human	Esophagus	ESCC	8.42e-18	1.20e+00	0.1177
7153	TOP2A	P4T-E	Human	Esophagus	ESCC	1.77e-09	5.80e-01	0.1323
7153	TOP2A	P5T-E	Human	Esophagus	ESCC	6.46e-12	6.11e-01	0.1327
7153	TOP2A	P8T-E	Human	Esophagus	ESCC	1.03e-03	4.58e-01	0.0889

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:001603214	Breast	IDC	viral process	75/1434	415/18723	1.98e-12	4.02e-10	75
GO:001905814	Breast	IDC	viral life cycle	61/1434	317/18723	1.61e-11	2.77e-09	61
GO:001907914	Breast	IDC	viral genome replication	32/1434	131/18723	2.82e-09	2.46e-07	32
GO:005079214	Breast	IDC	regulation of viral process	36/1434	164/18723	6.55e-09	5.03e-07	36
GO:190390014	Breast	IDC	regulation of viral life cycle	30/1434	148/18723	7.25e-07	3.35e-05	30
GO:004506913	Breast	IDC	regulation of viral genome replication	20/1434	85/18723	4.77e-06	1.63e-04	20
GO:004852413	Breast	IDC	positive regulation of viral process	17/1434	65/18723	5.31e-06	1.75e-04	17
GO:00450706	Breast	IDC	positive regulation of viral genome replication	9/1434	30/18723	2.89e-04	4.39e-03	9
GO:00485117	Breast	IDC	rhythmic process	38/1434	298/18723	1.34e-03	1.39e-02	38
GO:00330445	Breast	IDC	regulation of chromosome organization	26/1434	187/18723	2.22e-03	2.06e-02	26
GO:001603224	Breast	DCIS	viral process	73/1390	415/18723	3.40e-12	6.88e-10	73
GO:001905824	Breast	DCIS	viral life cycle	59/1390	317/18723	4.05e-11	5.74e-09	59
GO:001907923	Breast	DCIS	viral genome replication	30/1390	131/18723	2.12e-08	1.45e-06	30
GO:005079222	Breast	DCIS	regulation of viral process	34/1390	164/18723	3.58e-08	2.30e-06	34
GO:190390022	Breast	DCIS	regulation of viral life cycle	28/1390	148/18723	3.79e-06	1.16e-04	28
GO:004852421	Breast	DCIS	positive regulation of viral process	16/1390	65/18723	1.56e-05	3.79e-04	16
GO:004506923	Breast	DCIS	regulation of viral genome replication	18/1390	85/18723	4.23e-05	8.98e-04	18
GO:004507012	Breast	DCIS	positive regulation of viral genome replication	8/1390	30/18723	1.21e-03	1.28e-02	8
GO:004851113	Breast	DCIS	rhythmic process	37/1390	298/18723	1.44e-03	1.47e-02	37
GO:003304412	Breast	DCIS	regulation of chromosome organization	26/1390	187/18723	1.44e-03	1.47e-02	26

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa01524	Colorectum	MSS	Platinum drug resistance	25/1875	73/8465	1.17e-02	3.99e-02	2.44e-02	25
hsa015241	Colorectum	MSS	Platinum drug resistance	25/1875	73/8465	1.17e-02	3.99e-02	2.44e-02	25
hsa015247	Esophagus	ESCC	Platinum drug resistance	56/4205	73/8465	1.85e-06	1.13e-05	5.78e-06	56
hsa0152414	Esophagus	ESCC	Platinum drug resistance	56/4205	73/8465	1.85e-06	1.13e-05	5.78e-06	56
hsa015242	Liver	HCC	Platinum drug resistance	52/4020	73/8465	3.14e-05	1.88e-04	1.04e-04	52
hsa015243	Liver	HCC	Platinum drug resistance	52/4020	73/8465	3.14e-05	1.88e-04	1.04e-04	52
hsa015246	Oral cavity	OSCC	Platinum drug resistance	51/3704	73/8465	5.41e-06	2.75e-05	1.40e-05	51
hsa0152413	Oral cavity	OSCC	Platinum drug resistance	51/3704	73/8465	5.41e-06	2.75e-05	1.40e-05	51

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

TOP2A

SNV

Missense_Mutation

novel

c.4138N>A

p.Glu1380Lys

p.E1380K

P11388

protein_coding

tolerated(0.53)

benign(0.01)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

TOP2A

SNV

Missense_Mutation

c.570N>G

p.Phe190Leu

p.F190L

P11388

protein_coding

tolerated(0.11)

possibly_damaging(0.511)

TCGA-A2-A0CX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

TOP2A

SNV

Missense_Mutation

rs777230505

c.3644N>A

p.Arg1215His

p.R1215H

P11388

protein_coding

tolerated(0.55)

benign(0)

TCGA-AQ-A0Y5-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cytoxan

TOP2A

SNV

Missense_Mutation

c.2843A>G

p.Glu948Gly

p.E948G

P11388

protein_coding

deleterious(0.03)

benign(0.05)

TCGA-E9-A1RD-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

TOP2A

insertion

Nonsense_Mutation

novel

c.1399_1400insTTGGTTAAATTGAGGATACTTACGTTTGCTCTTATTTCAT

p.Thr467IlefsTer3

p.T467Ifs*3

P11388

protein_coding

TCGA-A8-A06P-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unspecific

TOP2A

insertion

Frame_Shift_Ins

novel

c.2071_2072insGCTTATACTTTCAC

p.Thr691SerfsTer8

p.T691Sfs*8

P11388

protein_coding

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TOP2A

insertion

Nonsense_Mutation

novel

c.1736_1737insTGTTTCAACTGGCTAAA

p.Lys579AsnfsTer6

p.K579Nfs*6

P11388

protein_coding

TCGA-AR-A0U2-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

tamoxiphen

TOP2A

SNV

Missense_Mutation

c.4144G>C

p.Asp1382His

p.D1382H

P11388

protein_coding

deleterious(0.01)

benign(0.146)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TOP2A

SNV

Missense_Mutation

c.1794G>T

p.Trp598Cys

p.W598C

P11388

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-LP-A4AX-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TOP2A

insertion

Frame_Shift_Ins

novel

c.4236_4237insGTTTGTAATTTCAGTTTCATCTGGGA

p.Asn1413ValfsTer11

p.N1413Vfs*11

P11388

protein_coding

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID	Symbol	Category	Interaction Types	Drug Claim Name	Drug Name	PMIDs
7153	TOP2A	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, ENZYME	inhibitor	CHEMBL1186894	AMRUBICIN
7153	TOP2A	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, ENZYME		EPIPODOPHYLLOTOXIN 4-(MORPHOLINE)CARBAMATE	CHEMBL1773343	21489802
7153	TOP2A	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, ENZYME		DTS-201
7153	TOP2A	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, ENZYME		DOXORUBICIN	DOXORUBICIN
7153	TOP2A	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, ENZYME		ANTHRACYCLINE		14978790,15068318
7153	TOP2A	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, ENZYME		BECATECARIN	BECATECARIN
7153	TOP2A	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, ENZYME		VORELOXIN	VOSAROXIN
7153	TOP2A	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, ENZYME		DOXORUBICIN	DOXORUBICIN
7153	TOP2A	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, ENZYME		ELLIPTECINE	ELLIPTECINE	18816045,19783445
7153	TOP2A	DRUGGABLE GENOME, CLINICALLY ACTIONABLE, ENZYME		DOXORUBICIN	DOXORUBICIN

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