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: CTNNA3

Gene summary for CTNNA3

Gene summary.

Gene information	Species	Human
	Gene symbol	CTNNA3
	Gene ID	29119
	Gene name	catenin alpha 3
	Gene Alias	ARVD13
	Cytomap	10q21.3
	Gene Type	protein-coding
	GO ID	GO:0001508
	UniProtAcc	A8K141

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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
29119	CTNNA3	HTA11_347_2000001011	Human	Colorectum	AD	8.73e-05	2.68e-01	-0.1954
29119	CTNNA3	HTA11_3361_2000001011	Human	Colorectum	AD	3.64e-04	3.84e-01	-0.1207
29119	CTNNA3	HTA11_83_2000001011	Human	Colorectum	SER	1.69e-03	2.78e-01	-0.1526
29119	CTNNA3	HTA11_696_2000001011	Human	Colorectum	AD	1.00e-06	3.10e-01	-0.1464
29119	CTNNA3	HTA11_866_2000001011	Human	Colorectum	AD	1.43e-02	1.53e-01	-0.1001
29119	CTNNA3	HTA11_1391_2000001011	Human	Colorectum	AD	1.76e-05	2.77e-01	-0.059
29119	CTNNA3	HTA11_2992_2000001011	Human	Colorectum	SER	1.87e-03	3.78e-01	-0.1706
29119	CTNNA3	HTA11_6818_2000001011	Human	Colorectum	AD	1.70e-03	4.45e-01	0.0112
29119	CTNNA3	HTA11_99999965062_69753	Human	Colorectum	MSI-H	4.94e-04	5.88e-01	0.3487
29119	CTNNA3	AEH-subject1	Human	Endometrium	AEH	1.66e-03	1.17e-01	-0.3059
29119	CTNNA3	HTA12-23-1	Human	Pancreas	PDAC	3.41e-03	5.19e-01	0.3405
29119	CTNNA3	HTA12-26-1	Human	Pancreas	PDAC	9.77e-13	6.82e-01	0.3728
29119	CTNNA3	HTA12-29-1	Human	Pancreas	PDAC	3.38e-23	6.11e-01	0.3722

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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

∗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:0007015	Colorectum	AD	actin filament organization	167/3918	442/18723	1.65e-16	7.94e-14	167
GO:0032970	Colorectum	AD	regulation of actin filament-based process	142/3918	397/18723	4.05e-12	5.90e-10	142
GO:0034109	Colorectum	AD	homotypic cell-cell adhesion	40/3918	90/18723	4.37e-07	1.67e-05	40
GO:0098901	Colorectum	AD	regulation of cardiac muscle cell action potential	15/3918	27/18723	8.20e-05	1.29e-03	15
GO:0098911	Colorectum	AD	regulation of ventricular cardiac muscle cell action potential	9/3918	12/18723	9.01e-05	1.38e-03	9
GO:0030048	Colorectum	AD	actin filament-based movement	44/3918	127/18723	2.31e-04	2.99e-03	44
GO:0090257	Colorectum	AD	regulation of muscle system process	73/3918	252/18723	1.46e-03	1.24e-02	73
GO:0086004	Colorectum	AD	regulation of cardiac muscle cell contraction	15/3918	34/18723	1.96e-03	1.58e-02	15
GO:00070151	Colorectum	SER	actin filament organization	134/2897	442/18723	1.39e-15	5.70e-13	134
GO:00329701	Colorectum	SER	regulation of actin filament-based process	115/2897	397/18723	4.16e-12	8.80e-10	115
GO:00341091	Colorectum	SER	homotypic cell-cell adhesion	32/2897	90/18723	2.23e-06	9.31e-05	32
GO:00300481	Colorectum	SER	actin filament-based movement	38/2897	127/18723	2.80e-05	7.56e-04	38
GO:00989011	Colorectum	SER	regulation of cardiac muscle cell action potential	12/2897	27/18723	3.27e-04	5.22e-03	12
GO:00902571	Colorectum	SER	regulation of muscle system process	60/2897	252/18723	3.28e-04	5.22e-03	60
GO:00989111	Colorectum	SER	regulation of ventricular cardiac muscle cell action potential	7/2897	12/18723	8.12e-04	1.01e-02	7
GO:0003012	Colorectum	SER	muscle system process	92/2897	452/18723	2.98e-03	2.63e-02	92
GO:00860041	Colorectum	SER	regulation of cardiac muscle cell contraction	12/2897	34/18723	3.60e-03	3.03e-02	12
GO:0055117	Colorectum	SER	regulation of cardiac muscle contraction	21/2897	77/18723	5.54e-03	4.09e-02	21
GO:00341093	Colorectum	MSI-H	homotypic cell-cell adhesion	20/1319	90/18723	3.43e-06	1.89e-04	20
GO:00329703	Colorectum	MSI-H	regulation of actin filament-based process	49/1319	397/18723	8.99e-05	2.90e-03	49

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05100	Colorectum	AD	Bacterial invasion of epithelial cells	44/2092	77/8465	1.13e-09	2.22e-08	1.42e-08	44
hsa04520	Colorectum	AD	Adherens junction	50/2092	93/8465	1.52e-09	2.83e-08	1.81e-08	50
hsa05213	Colorectum	AD	Endometrial cancer	29/2092	58/8465	2.69e-05	2.57e-04	1.64e-04	29
hsa04670	Colorectum	AD	Leukocyte transendothelial migration	41/2092	114/8465	4.60e-03	2.20e-02	1.40e-02	41
hsa051001	Colorectum	AD	Bacterial invasion of epithelial cells	44/2092	77/8465	1.13e-09	2.22e-08	1.42e-08	44
hsa045201	Colorectum	AD	Adherens junction	50/2092	93/8465	1.52e-09	2.83e-08	1.81e-08	50
hsa052131	Colorectum	AD	Endometrial cancer	29/2092	58/8465	2.69e-05	2.57e-04	1.64e-04	29
hsa046701	Colorectum	AD	Leukocyte transendothelial migration	41/2092	114/8465	4.60e-03	2.20e-02	1.40e-02	41
hsa051002	Colorectum	SER	Bacterial invasion of epithelial cells	36/1580	77/8465	1.56e-08	3.45e-07	2.50e-07	36
hsa045202	Colorectum	SER	Adherens junction	37/1580	93/8465	1.54e-06	2.35e-05	1.71e-05	37
hsa046702	Colorectum	SER	Leukocyte transendothelial migration	37/1580	114/8465	2.77e-04	2.56e-03	1.86e-03	37
hsa052132	Colorectum	SER	Endometrial cancer	20/1580	58/8465	3.05e-03	2.11e-02	1.53e-02	20
hsa051003	Colorectum	SER	Bacterial invasion of epithelial cells	36/1580	77/8465	1.56e-08	3.45e-07	2.50e-07	36
hsa045203	Colorectum	SER	Adherens junction	37/1580	93/8465	1.54e-06	2.35e-05	1.71e-05	37
hsa046703	Colorectum	SER	Leukocyte transendothelial migration	37/1580	114/8465	2.77e-04	2.56e-03	1.86e-03	37
hsa052133	Colorectum	SER	Endometrial cancer	20/1580	58/8465	3.05e-03	2.11e-02	1.53e-02	20
hsa045206	Colorectum	MSI-H	Adherens junction	22/797	93/8465	3.71e-05	5.47e-04	4.58e-04	22
hsa051006	Colorectum	MSI-H	Bacterial invasion of epithelial cells	15/797	77/8465	4.86e-03	4.63e-02	3.88e-02	15
hsa045207	Colorectum	MSI-H	Adherens junction	22/797	93/8465	3.71e-05	5.47e-04	4.58e-04	22
hsa051007	Colorectum	MSI-H	Bacterial invasion of epithelial cells	15/797	77/8465	4.86e-03	4.63e-02	3.88e-02	15

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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

CTNNA3

SNV

Missense_Mutation

c.1388N>G

p.Ala463Gly

p.A463G

Q9UI47

protein_coding

deleterious(0.02)

probably_damaging(0.982)

TCGA-A2-A04Q-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

CTNNA3

SNV

Missense_Mutation

rs369033938

c.1628N>A

p.Arg543Gln

p.R543Q

Q9UI47

protein_coding

deleterious(0.02)

probably_damaging(0.981)

TCGA-A8-A09Q-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

CTNNA3

SNV

Missense_Mutation

rs373081692

c.2501N>A

p.Arg834Gln

p.R834Q

Q9UI47

protein_coding

deleterious(0.01)

benign(0.24)

TCGA-A8-A0A9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

CTNNA3

SNV

Missense_Mutation

c.650N>A

p.Leu217His

p.L217H

Q9UI47

protein_coding

deleterious(0)

possibly_damaging(0.608)

TCGA-AR-A251-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

CTNNA3

SNV

Missense_Mutation

rs375721994

c.1006N>T

p.Arg336Cys

p.R336C

Q9UI47

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-C8-A1HI-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

CTNNA3

SNV

Missense_Mutation

c.1956N>C

p.Gln652His

p.Q652H

Q9UI47

protein_coding

tolerated(0.16)

probably_damaging(0.986)

TCGA-E2-A1IN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

CTNNA3

SNV

Missense_Mutation

novel

c.2136G>T

p.Met712Ile

p.M712I

Q9UI47

protein_coding

deleterious(0)

probably_damaging(0.954)

TCGA-LQ-A4E4-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

CTNNA3

insertion

Nonsense_Mutation

novel

c.1777_1778insCATTTGTGTAAGTTATAACCAAATACA

p.Leu593delinsSerPheValTerValIleThrLysTyrIle

p.L593delinsSFV*VITKYI

Q9UI47

protein_coding

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CTNNA3

deletion

Frame_Shift_Del

novel

c.1110_1111delNN

p.Asp372ProfsTer29

p.D372Pfs*29

Q9UI47

protein_coding

TCGA-OL-A66P-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

CTNNA3

SNV

Missense_Mutation

novel

c.1810A>G

p.Asn604Asp

p.N604D

Q9UI47

protein_coding

tolerated(0.14)

benign(0)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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
29119	CTNNA3	NA		antidepressants

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