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: ACTR2

Gene summary for ACTR2

Gene summary.

Gene information	Species	Human
	Gene symbol	ACTR2
	Gene ID	10097
	Gene name	actin related protein 2
	Gene Alias	ARP2
	Cytomap	2p14
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P61160

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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
10097	ACTR2	HTA11_1938_2000001011	Human	Colorectum	AD	1.06e-04	5.85e-01	-0.0811
10097	ACTR2	HTA11_78_2000001011	Human	Colorectum	AD	6.90e-09	6.42e-01	-0.1088
10097	ACTR2	HTA11_347_2000001011	Human	Colorectum	AD	2.89e-29	9.25e-01	-0.1954
10097	ACTR2	HTA11_411_2000001011	Human	Colorectum	SER	1.62e-03	7.85e-01	-0.2602
10097	ACTR2	HTA11_2112_2000001011	Human	Colorectum	SER	4.20e-02	6.54e-01	-0.2196
10097	ACTR2	HTA11_1391_2000001011	Human	Colorectum	AD	4.49e-05	5.29e-01	-0.059
10097	ACTR2	HTA11_99999965104_69814	Human	Colorectum	MSS	8.18e-09	7.22e-01	0.281
10097	ACTR2	A015-C-203	Human	Colorectum	FAP	3.93e-28	-4.57e-01	-0.1294
10097	ACTR2	A015-C-204	Human	Colorectum	FAP	9.41e-04	-1.74e-01	-0.0228
10097	ACTR2	A014-C-040	Human	Colorectum	FAP	9.70e-04	-5.24e-01	-0.1184
10097	ACTR2	A002-C-201	Human	Colorectum	FAP	5.06e-08	-1.30e-01	0.0324
10097	ACTR2	A002-C-203	Human	Colorectum	FAP	8.11e-04	-6.35e-02	0.2786
10097	ACTR2	A001-C-119	Human	Colorectum	FAP	1.71e-10	-4.84e-01	-0.1557
10097	ACTR2	A001-C-108	Human	Colorectum	FAP	4.84e-17	-2.44e-01	-0.0272
10097	ACTR2	A002-C-205	Human	Colorectum	FAP	1.33e-15	-2.40e-01	-0.1236
10097	ACTR2	A001-C-104	Human	Colorectum	FAP	8.60e-09	-2.75e-01	0.0184
10097	ACTR2	A015-C-005	Human	Colorectum	FAP	4.31e-03	-2.45e-01	-0.0336
10097	ACTR2	A015-C-006	Human	Colorectum	FAP	6.67e-13	-4.70e-01	-0.0994
10097	ACTR2	A015-C-106	Human	Colorectum	FAP	8.79e-16	-3.74e-01	-0.0511
10097	ACTR2	A002-C-114	Human	Colorectum	FAP	2.54e-14	-4.00e-01	-0.1561

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
Prostate		BPH: Benign Prostatic Hyperplasia
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:0048285	Liver	HCC	organelle fission	254/7958	488/18723	1.07e-05	1.23e-04	254
GO:003431421	Liver	HCC	Arp2/3 complex-mediated actin nucleation	30/7958	39/18723	1.28e-05	1.43e-04	30
GO:003083812	Liver	HCC	positive regulation of actin filament polymerization	63/7958	99/18723	1.76e-05	1.89e-04	63
GO:009758121	Liver	HCC	lamellipodium organization	58/7958	90/18723	2.16e-05	2.30e-04	58
GO:000091011	Liver	HCC	cytokinesis	100/7958	173/18723	3.38e-05	3.39e-04	100
GO:190274521	Liver	HCC	positive regulation of lamellipodium organization	28/7958	37/18723	4.26e-05	4.16e-04	28
GO:005105411	Liver	HCC	positive regulation of DNA metabolic process	113/7958	201/18723	5.76e-05	5.33e-04	113
GO:009730522	Liver	HCC	response to alcohol	138/7958	253/18723	6.91e-05	6.26e-04	138
GO:200102211	Liver	HCC	positive regulation of response to DNA damage stimulus	64/7958	105/18723	1.03e-04	8.88e-04	64
GO:00343411	Liver	HCC	response to interferon-gamma	82/7958	141/18723	1.25e-04	1.03e-03	82
GO:00713461	Liver	HCC	cellular response to interferon-gamma	70/7958	118/18723	1.66e-04	1.32e-03	70
GO:004501011	Liver	HCC	actin nucleation	35/7958	52/18723	2.63e-04	1.94e-03	35
GO:190274321	Liver	HCC	regulation of lamellipodium organization	36/7958	54/18723	2.88e-04	2.07e-03	36
GO:006164011	Liver	HCC	cytoskeleton-dependent cytokinesis	60/7958	100/18723	3.09e-04	2.20e-03	60
GO:001072011	Liver	HCC	positive regulation of cell development	155/7958	298/18723	5.39e-04	3.48e-03	155
GO:00062824	Liver	HCC	regulation of DNA repair	74/7958	130/18723	6.27e-04	3.89e-03	74
GO:0000280	Liver	HCC	nuclear division	220/7958	439/18723	6.90e-04	4.25e-03	220
GO:001059221	Liver	HCC	positive regulation of lamellipodium assembly	21/7958	29/18723	1.07e-03	6.16e-03	21
GO:003003221	Liver	HCC	lamellipodium assembly	44/7958	72/18723	1.10e-03	6.32e-03	44
GO:00063021	Liver	HCC	double-strand break repair	131/7958	251/18723	1.17e-03	6.54e-03	131

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04144	Colorectum	AD	Endocytosis	111/2092	251/8465	5.95e-12	1.42e-10	9.08e-11	111
hsa05131	Colorectum	AD	Shigellosis	109/2092	247/8465	1.09e-11	2.44e-10	1.55e-10	109
hsa05100	Colorectum	AD	Bacterial invasion of epithelial cells	44/2092	77/8465	1.13e-09	2.22e-08	1.42e-08	44
hsa04530	Colorectum	AD	Tight junction	76/2092	169/8465	5.49e-09	9.69e-08	6.18e-08	76
hsa05132	Colorectum	AD	Salmonella infection	102/2092	249/8465	7.65e-09	1.28e-07	8.17e-08	102
hsa04666	Colorectum	AD	Fc gamma R-mediated phagocytosis	46/2092	97/8465	9.10e-07	1.22e-05	7.77e-06	46
hsa05130	Colorectum	AD	Pathogenic Escherichia coli infection	79/2092	197/8465	1.05e-06	1.36e-05	8.65e-06	79
hsa05135	Colorectum	AD	Yersinia infection	58/2092	137/8465	3.90e-06	4.35e-05	2.78e-05	58
hsa04810	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa041441	Colorectum	AD	Endocytosis	111/2092	251/8465	5.95e-12	1.42e-10	9.08e-11	111
hsa051311	Colorectum	AD	Shigellosis	109/2092	247/8465	1.09e-11	2.44e-10	1.55e-10	109
hsa051001	Colorectum	AD	Bacterial invasion of epithelial cells	44/2092	77/8465	1.13e-09	2.22e-08	1.42e-08	44
hsa045301	Colorectum	AD	Tight junction	76/2092	169/8465	5.49e-09	9.69e-08	6.18e-08	76
hsa051321	Colorectum	AD	Salmonella infection	102/2092	249/8465	7.65e-09	1.28e-07	8.17e-08	102
hsa046661	Colorectum	AD	Fc gamma R-mediated phagocytosis	46/2092	97/8465	9.10e-07	1.22e-05	7.77e-06	46
hsa051301	Colorectum	AD	Pathogenic Escherichia coli infection	79/2092	197/8465	1.05e-06	1.36e-05	8.65e-06	79
hsa051351	Colorectum	AD	Yersinia infection	58/2092	137/8465	3.90e-06	4.35e-05	2.78e-05	58
hsa048101	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa051312	Colorectum	SER	Shigellosis	87/1580	247/8465	3.07e-10	7.27e-09	5.28e-09	87
hsa051002	Colorectum	SER	Bacterial invasion of epithelial cells	36/1580	77/8465	1.56e-08	3.45e-07	2.50e-07	36

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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

ACTR2

SNV

Missense_Mutation

novel

c.743N>A

p.Ser248Tyr

p.S248Y

P61160

protein_coding

deleterious(0)

possibly_damaging(0.725)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ACTR2

SNV

Missense_Mutation

rs746974315

c.1196N>A

p.Arg399Gln

p.R399Q

P61160

protein_coding

deleterious_low_confidence(0.01)

benign(0)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ACTR2

SNV

Missense_Mutation

c.1043G>A

p.Arg348His

p.R348H

P61160

protein_coding

deleterious(0.02)

possibly_damaging(0.807)

TCGA-AA-3947-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

ACTR2

SNV

Missense_Mutation

rs17851188

c.529N>A

p.Gly177Ser

p.G177S

P61160

protein_coding

tolerated(0.08)

possibly_damaging(0.706)

TCGA-AA-A01V-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

ACTR2

SNV

Missense_Mutation

c.254G>A

p.Arg85Gln

p.R85Q

P61160

protein_coding

tolerated(0.42)

possibly_damaging(0.899)

TCGA-EI-6917-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

5fluorouracil+oxaciplatina+l-folinian

ACTR2

SNV

Missense_Mutation

novel

c.1061G>A

p.Arg354His

p.R354H

P61160

protein_coding

deleterious(0.03)

possibly_damaging(0.852)

TCGA-EI-6917-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

5fluorouracil+oxaciplatina+l-folinian

ACTR2

SNV

Missense_Mutation

novel

c.668N>C

p.Glu223Ala

p.E223A

P61160

protein_coding

deleterious(0.01)

benign(0.229)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

ACTR2

SNV

Missense_Mutation

c.946N>A

p.Pro316Thr

p.P316T

P61160

protein_coding

deleterious(0)

possibly_damaging(0.767)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

ACTR2

SNV

Missense_Mutation

novel

c.1048N>A

p.Glu350Lys

p.E350K

P61160

protein_coding

tolerated(0.64)

probably_damaging(0.999)

TCGA-AJ-A3EK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

ACTR2

SNV

Missense_Mutation

c.655N>T

p.Arg219Cys

p.R219C

P61160

protein_coding

deleterious(0)

benign(0.186)

TCGA-AJ-A3EL-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

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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
10097	ACTR2	NA		ETOPOSIDE	ETOPOSIDE	15900709
10097	ACTR2	NA		MCP-1		16004967

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