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: CTNNA1

Gene summary for CTNNA1

Gene summary.

Gene information	Species	Human
	Gene symbol	CTNNA1
	Gene ID	1495
	Gene name	catenin alpha 1
	Gene Alias	CAP102
	Cytomap	5q31.2
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	G3XAM7

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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
1495	CTNNA1	CA_HPV_1	Human	Cervix	CC	2.31e-06	-1.91e-01	0.0264
1495	CTNNA1	N_HPV_1	Human	Cervix	N_HPV	3.96e-02	-2.28e-01	0.0079
1495	CTNNA1	CCI_1	Human	Cervix	CC	4.31e-02	5.98e-01	0.528
1495	CTNNA1	CCI_2	Human	Cervix	CC	1.42e-15	1.69e+00	0.5249
1495	CTNNA1	CCI_3	Human	Cervix	CC	3.91e-12	1.00e+00	0.516
1495	CTNNA1	H2	Human	Cervix	HSIL_HPV	4.43e-09	3.07e-01	0.0632
1495	CTNNA1	L1	Human	Cervix	CC	2.92e-02	-2.37e-01	0.0802
1495	CTNNA1	HTA11_3410_2000001011	Human	Colorectum	AD	1.06e-06	-4.30e-01	0.0155
1495	CTNNA1	HTA11_1938_2000001011	Human	Colorectum	AD	2.87e-06	5.50e-01	-0.0811
1495	CTNNA1	HTA11_78_2000001011	Human	Colorectum	AD	1.04e-04	5.15e-01	-0.1088
1495	CTNNA1	HTA11_347_2000001011	Human	Colorectum	AD	4.00e-17	7.10e-01	-0.1954
1495	CTNNA1	HTA11_411_2000001011	Human	Colorectum	SER	2.26e-09	1.19e+00	-0.2602
1495	CTNNA1	HTA11_2112_2000001011	Human	Colorectum	SER	1.41e-02	6.06e-01	-0.2196
1495	CTNNA1	HTA11_9341_2000001011	Human	Colorectum	SER	5.89e-03	-6.07e-01	-0.00410000000000005
1495	CTNNA1	HTA11_99999974143_84620	Human	Colorectum	MSS	2.08e-05	-3.68e-01	0.3005
1495	CTNNA1	F007	Human	Colorectum	FAP	4.74e-02	-1.53e-01	0.1176
1495	CTNNA1	A001-C-207	Human	Colorectum	FAP	2.40e-04	-2.87e-01	0.1278
1495	CTNNA1	A015-C-203	Human	Colorectum	FAP	2.72e-44	-6.33e-01	-0.1294
1495	CTNNA1	A015-C-204	Human	Colorectum	FAP	3.24e-10	-4.45e-01	-0.0228
1495	CTNNA1	A014-C-040	Human	Colorectum	FAP	2.44e-08	-6.45e-01	-0.1184

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:200123310	Cervix	CC	regulation of apoptotic signaling pathway	96/2311	356/18723	4.08e-14	3.05e-11	96
GO:000701510	Cervix	CC	actin filament organization	109/2311	442/18723	4.92e-13	2.45e-10	109
GO:00071639	Cervix	CC	establishment or maintenance of cell polarity	63/2311	218/18723	4.25e-11	8.76e-09	63
GO:00452169	Cervix	CC	cell-cell junction organization	53/2311	200/18723	3.83e-08	2.53e-06	53
GO:00345048	Cervix	CC	protein localization to nucleus	68/2311	290/18723	9.91e-08	5.25e-06	68
GO:00072295	Cervix	CC	integrin-mediated signaling pathway	34/2311	107/18723	1.01e-07	5.25e-06	34
GO:200123410	Cervix	CC	negative regulation of apoptotic signaling pathway	56/2311	224/18723	1.39e-07	6.70e-06	56
GO:20012357	Cervix	CC	positive regulation of apoptotic signaling pathway	37/2311	126/18723	2.70e-07	1.12e-05	37
GO:00075689	Cervix	CC	aging	75/2311	339/18723	2.75e-07	1.13e-05	75
GO:00343298	Cervix	CC	cell junction assembly	88/2311	420/18723	3.42e-07	1.38e-05	88
GO:00614588	Cervix	CC	reproductive system development	87/2311	427/18723	1.37e-06	4.55e-05	87
GO:00070439	Cervix	CC	cell-cell junction assembly	39/2311	146/18723	1.86e-06	5.94e-05	39
GO:00486088	Cervix	CC	reproductive structure development	86/2311	424/18723	1.90e-06	5.97e-05	86
GO:009719110	Cervix	CC	extrinsic apoptotic signaling pathway	52/2311	219/18723	2.06e-06	6.34e-05	52
GO:00432978	Cervix	CC	apical junction assembly	24/2311	78/18723	1.36e-05	2.73e-04	24
GO:00310996	Cervix	CC	regeneration	46/2311	198/18723	1.43e-05	2.84e-04	46
GO:00615647	Cervix	CC	axon development	89/2311	467/18723	1.71e-05	3.27e-04	89
GO:00512713	Cervix	CC	negative regulation of cellular component movement	73/2311	367/18723	2.22e-05	3.95e-04	73
GO:200123610	Cervix	CC	regulation of extrinsic apoptotic signaling pathway	37/2311	151/18723	2.80e-05	4.65e-04	37
GO:00400133	Cervix	CC	negative regulation of locomotion	76/2311	391/18723	3.47e-05	5.60e-04	76

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0452020	Cervix	CC	Adherens junction	33/1267	93/8465	6.99e-07	7.31e-06	4.32e-06	33
hsa0467020	Cervix	CC	Leukocyte transendothelial migration	36/1267	114/8465	5.22e-06	4.83e-05	2.86e-05	36
hsa043908	Cervix	CC	Hippo signaling pathway	40/1267	157/8465	3.64e-04	1.82e-03	1.07e-03	40
hsa0510020	Cervix	CC	Bacterial invasion of epithelial cells	23/1267	77/8465	6.25e-04	2.93e-03	1.73e-03	23
hsa0521310	Cervix	CC	Endometrial cancer	18/1267	58/8465	1.46e-03	6.30e-03	3.73e-03	18
hsa04520110	Cervix	CC	Adherens junction	33/1267	93/8465	6.99e-07	7.31e-06	4.32e-06	33
hsa04670110	Cervix	CC	Leukocyte transendothelial migration	36/1267	114/8465	5.22e-06	4.83e-05	2.86e-05	36
hsa0439013	Cervix	CC	Hippo signaling pathway	40/1267	157/8465	3.64e-04	1.82e-03	1.07e-03	40
hsa05100110	Cervix	CC	Bacterial invasion of epithelial cells	23/1267	77/8465	6.25e-04	2.93e-03	1.73e-03	23
hsa0521313	Cervix	CC	Endometrial cancer	18/1267	58/8465	1.46e-03	6.30e-03	3.73e-03	18
hsa0467025	Cervix	HSIL_HPV	Leukocyte transendothelial migration	16/459	114/8465	4.04e-04	3.49e-03	2.82e-03	16
hsa054127	Cervix	HSIL_HPV	Arrhythmogenic right ventricular cardiomyopathy	10/459	77/8465	8.34e-03	4.70e-02	3.80e-02	10
hsa0467035	Cervix	HSIL_HPV	Leukocyte transendothelial migration	16/459	114/8465	4.04e-04	3.49e-03	2.82e-03	16
hsa0541212	Cervix	HSIL_HPV	Arrhythmogenic right ventricular cardiomyopathy	10/459	77/8465	8.34e-03	4.70e-02	3.80e-02	10
hsa0510025	Cervix	N_HPV	Bacterial invasion of epithelial cells	10/349	77/8465	1.17e-03	7.93e-03	6.20e-03	10
hsa0467045	Cervix	N_HPV	Leukocyte transendothelial migration	12/349	114/8465	2.50e-03	1.45e-02	1.13e-02	12
hsa0510035	Cervix	N_HPV	Bacterial invasion of epithelial cells	10/349	77/8465	1.17e-03	7.93e-03	6.20e-03	10
hsa0467055	Cervix	N_HPV	Leukocyte transendothelial migration	12/349	114/8465	2.50e-03	1.45e-02	1.13e-02	12
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

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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

CTNNA1

SNV

Missense_Mutation

rs781520852

c.160N>T

p.Arg54Cys

p.R54C

P35221

protein_coding

tolerated(0.07)

possibly_damaging(0.873)

TCGA-AC-A3TM-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

CTNNA1

SNV

Missense_Mutation

c.1294G>C

p.Glu432Gln

p.E432Q

P35221

protein_coding

tolerated(0.07)

benign(0.405)

TCGA-AN-A0XW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

CTNNA1

SNV

Missense_Mutation

c.1673C>T

p.Ser558Leu

p.S558L

P35221

protein_coding

deleterious(0)

benign(0.295)

TCGA-BH-A18U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

CTNNA1

insertion

Nonsense_Mutation

novel

c.451_452insAACAAATAAAAGAATGAATGATCTCCATCT

p.Leu151delinsGlnGlnIleLysGluTerMetIleSerIlePhe

p.L151delinsQQIKE*MISIF

P35221

protein_coding

TCGA-A2-A0CP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

CTNNA1

SNV

Missense_Mutation

c.2350G>A

p.Ala784Thr

p.A784T

P35221

protein_coding

tolerated(0.41)

benign(0.131)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CTNNA1

SNV

Missense_Mutation

novel

c.2411G>A

p.Gly804Asp

p.G804D

P35221

protein_coding

deleterious(0.01)

possibly_damaging(0.756)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CTNNA1

SNV

Missense_Mutation

c.1939N>C

p.Asp647His

p.D647H

P35221

protein_coding

deleterious(0.01)

probably_damaging(0.95)

TCGA-EK-A2RA-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

CTNNA1

SNV

Missense_Mutation

novel

c.2163N>C

p.Met721Ile

p.M721I

P35221

protein_coding

deleterious(0.04)

possibly_damaging(0.516)

TCGA-HM-A4S6-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

CTNNA1

SNV

Missense_Mutation

novel

c.1027G>A

p.Ala343Thr

p.A343T

P35221

protein_coding

deleterious(0.02)

benign(0.12)

TCGA-5M-AAT6-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Unknown

CTNNA1

SNV

Missense_Mutation

c.2397N>T

p.Glu799Asp

p.E799D

P35221

protein_coding

tolerated(0.88)

benign(0.071)

TCGA-A6-6780-01

Colorectum

colon adenocarcinoma

Male

>=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

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