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: CTNNA2

Gene summary for CTNNA2

Gene summary.

Gene information	Species	Human
	Gene symbol	CTNNA2
	Gene ID	1496
	Gene name	catenin alpha 2
	Gene Alias	CAP-R
	Cytomap	2p12
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	P26232

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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
1496	CTNNA2	HTA11_3410_2000001011	Human	Colorectum	AD	7.77e-04	2.19e-01	0.0155
1496	CTNNA2	HTA11_2487_2000001011	Human	Colorectum	SER	2.98e-04	2.47e-01	-0.1808
1496	CTNNA2	HTA11_2951_2000001011	Human	Colorectum	AD	1.53e-09	8.38e-01	0.0216
1496	CTNNA2	HTA11_1938_2000001011	Human	Colorectum	AD	1.02e-10	4.99e-01	-0.0811
1496	CTNNA2	HTA11_347_2000001011	Human	Colorectum	AD	7.45e-04	2.16e-01	-0.1954
1496	CTNNA2	HTA11_411_2000001011	Human	Colorectum	SER	3.02e-04	4.69e-01	-0.2602
1496	CTNNA2	HTA11_3361_2000001011	Human	Colorectum	AD	2.61e-07	4.38e-01	-0.1207
1496	CTNNA2	HTA11_696_2000001011	Human	Colorectum	AD	9.52e-26	5.38e-01	-0.1464
1496	CTNNA2	HTA11_866_2000001011	Human	Colorectum	AD	5.11e-07	2.72e-01	-0.1001
1496	CTNNA2	HTA11_1391_2000001011	Human	Colorectum	AD	6.71e-13	8.44e-01	-0.059
1496	CTNNA2	HTA11_2992_2000001011	Human	Colorectum	SER	2.77e-05	5.09e-01	-0.1706
1496	CTNNA2	HTA11_5212_2000001011	Human	Colorectum	AD	9.71e-04	4.23e-01	-0.2061
1496	CTNNA2	HTA11_5216_2000001011	Human	Colorectum	SER	8.30e-11	6.37e-01	-0.1462
1496	CTNNA2	HTA11_10711_2000001011	Human	Colorectum	AD	2.98e-30	2.67e+00	0.0338
1496	CTNNA2	HTA11_7696_3000711011	Human	Colorectum	AD	2.13e-29	1.18e+00	0.0674
1496	CTNNA2	HTA11_99999973899_84307	Human	Colorectum	MSS	5.72e-04	5.59e-01	0.2585
1496	CTNNA2	HTA11_99999974143_84620	Human	Colorectum	MSS	3.64e-05	2.56e-01	0.3005
1496	CTNNA2	A015-C-203	Human	Colorectum	FAP	1.39e-14	7.63e-01	-0.1294
1496	CTNNA2	A002-C-201	Human	Colorectum	FAP	7.49e-06	5.41e-01	0.0324
1496	CTNNA2	A001-C-119	Human	Colorectum	FAP	3.06e-02	4.63e-01	-0.1557

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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:00308331	Colorectum	SER	regulation of actin filament polymerization	64/2897	172/18723	2.42e-12	5.70e-10	64
GO:00329701	Colorectum	SER	regulation of actin filament-based process	115/2897	397/18723	4.16e-12	8.80e-10	115
GO:00322711	Colorectum	SER	regulation of protein polymerization	78/2897	233/18723	5.71e-12	1.17e-09	78
GO:00512581	Colorectum	SER	protein polymerization	91/2897	297/18723	2.72e-11	5.06e-09	91
GO:00432541	Colorectum	SER	regulation of protein-containing complex assembly	119/2897	428/18723	3.34e-11	5.86e-09	119
GO:00329561	Colorectum	SER	regulation of actin cytoskeleton organization	104/2897	358/18723	3.68e-11	6.11e-09	104
GO:00308381	Colorectum	SER	positive regulation of actin filament polymerization	41/2897	99/18723	4.78e-10	5.68e-08	41
GO:19029051	Colorectum	SER	positive regulation of supramolecular fiber organization	68/2897	209/18723	5.17e-10	5.98e-08	68
GO:00322731	Colorectum	SER	positive regulation of protein polymerization	51/2897	138/18723	5.26e-10	5.98e-08	51
GO:00514951	Colorectum	SER	positive regulation of cytoskeleton organization	71/2897	226/18723	1.22e-09	1.27e-07	71
GO:00313341	Colorectum	SER	positive regulation of protein-containing complex assembly	73/2897	237/18723	1.89e-09	1.84e-07	73
GO:00106391	Colorectum	SER	negative regulation of organelle organization	90/2897	348/18723	3.14e-07	1.69e-05	90
GO:19029041	Colorectum	SER	negative regulation of supramolecular fiber organization	50/2897	167/18723	1.63e-06	7.23e-05	50
GO:00450101	Colorectum	SER	actin nucleation	22/2897	52/18723	3.25e-06	1.28e-04	22
GO:00514941	Colorectum	SER	negative regulation of cytoskeleton organization	48/2897	163/18723	4.34e-06	1.63e-04	48
GO:00343141	Colorectum	SER	Arp2/3 complex-mediated actin nucleation	17/2897	39/18723	2.64e-05	7.21e-04	17
GO:00511251	Colorectum	SER	regulation of actin nucleation	13/2897	30/18723	2.52e-04	4.23e-03	13
GO:00163581	Colorectum	SER	dendrite development	58/2897	243/18723	3.82e-04	5.81e-03	58
GO:00109751	Colorectum	SER	regulation of neuron projection development	92/2897	445/18723	1.85e-03	1.89e-02	92
GO:0048813	Colorectum	SER	dendrite morphogenesis	36/2897	146/18723	2.51e-03	2.33e-02	36

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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
hsa045204	Colorectum	MSS	Adherens junction	42/1875	93/8465	6.18e-07	9.01e-06	5.52e-06	42
hsa051004	Colorectum	MSS	Bacterial invasion of epithelial cells	36/1875	77/8465	1.41e-06	1.82e-05	1.11e-05	36
hsa052134	Colorectum	MSS	Endometrial cancer	27/1875	58/8465	3.18e-05	3.23e-04	1.98e-04	27
hsa04390	Colorectum	MSS	Hippo signaling pathway	48/1875	157/8465	8.32e-03	3.10e-02	1.90e-02	48

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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

CTNNA2

SNV

Missense_Mutation

rs778479901

c.1756G>A

p.Ala586Thr

p.A586T

P26232

protein_coding

tolerated(0.53)

benign(0.079)

TCGA-A2-A0YM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CTNNA2

SNV

Missense_Mutation

c.902N>T

p.Pro301Leu

p.P301L

P26232

protein_coding

deleterious(0)

probably_damaging(0.956)

TCGA-A8-A07P-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

5-fluorouracil

CTNNA2

SNV

Missense_Mutation

c.1498G>C

p.Val500Leu

p.V500L

P26232

protein_coding

tolerated(0.14)

benign(0.275)

TCGA-AO-A1KR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

CTNNA2

SNV

Missense_Mutation

c.2261N>T

p.Arg754Leu

p.R754L

P26232

protein_coding

deleterious(0)

possibly_damaging(0.787)

TCGA-AR-A1AJ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CTNNA2

SNV

Missense_Mutation

rs529691509

c.2792N>A

p.Arg931Gln

p.R931Q

P26232

protein_coding

deleterious(0.04)

probably_damaging(0.957)

TCGA-AR-A5QN-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

taxotere

CTNNA2

SNV

Missense_Mutation

c.441G>A

p.Met147Ile

p.M147I

P26232

protein_coding

tolerated(0.31)

benign(0.003)

TCGA-B6-A408-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

CTNNA2

SNV

Missense_Mutation

c.1081N>T

p.Pro361Ser

p.P361S

P26232

protein_coding

tolerated(0.74)

benign(0.045)

TCGA-BH-A0BP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CTNNA2

SNV

Missense_Mutation

c.1451N>C

p.Val484Ala

p.V484A

P26232

protein_coding

tolerated(0.77)

benign(0.017)

TCGA-D8-A1JK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CTNNA2

SNV

Missense_Mutation

c.578N>T

p.Arg193Ile

p.R193I

P26232

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-E2-A10C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

CTNNA2

SNV

Missense_Mutation

rs529691509

c.2792G>A

p.Arg931Gln

p.R931Q

P26232

protein_coding

deleterious(0.04)

probably_damaging(0.957)

TCGA-E9-A1R0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

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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
1496	CTNNA2	NA		Tumor necrosis factor alpha (TNF-alpha) inhibitors		27670765

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