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: PHACTR4

Gene summary for PHACTR4

Gene summary.

Gene information	Species	Human
	Gene symbol	PHACTR4
	Gene ID	65979
	Gene name	phosphatase and actin regulator 4
	Gene Alias	PPP1R124
	Cytomap	1p35.3
	Gene Type	protein-coding
	GO ID	GO:0001654
	UniProtAcc	Q8IZ21

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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
65979	PHACTR4	CA_HPV_1	Human	Cervix	CC	1.69e-02	-1.65e-01	0.0264
65979	PHACTR4	CCI_1	Human	Cervix	CC	2.54e-02	9.89e-01	0.528
65979	PHACTR4	CCI_2	Human	Cervix	CC	1.79e-02	5.78e-01	0.5249
65979	PHACTR4	CCI_3	Human	Cervix	CC	5.56e-03	5.11e-01	0.516
65979	PHACTR4	HTA11_3410_2000001011	Human	Colorectum	AD	1.28e-03	-1.99e-01	0.0155
65979	PHACTR4	HTA11_347_2000001011	Human	Colorectum	AD	1.05e-19	8.06e-01	-0.1954
65979	PHACTR4	HTA11_696_2000001011	Human	Colorectum	AD	8.46e-05	4.95e-01	-0.1464
65979	PHACTR4	HTA11_866_2000001011	Human	Colorectum	AD	3.49e-02	3.70e-01	-0.1001
65979	PHACTR4	HTA11_1391_2000001011	Human	Colorectum	AD	1.50e-04	5.16e-01	-0.059
65979	PHACTR4	F007	Human	Colorectum	FAP	3.08e-05	-4.41e-01	0.1176
65979	PHACTR4	A002-C-010	Human	Colorectum	FAP	2.65e-02	-1.55e-01	0.242
65979	PHACTR4	A001-C-207	Human	Colorectum	FAP	1.79e-06	-3.69e-01	0.1278
65979	PHACTR4	A015-C-203	Human	Colorectum	FAP	1.35e-32	-3.91e-01	-0.1294
65979	PHACTR4	A015-C-204	Human	Colorectum	FAP	2.86e-07	-2.95e-01	-0.0228
65979	PHACTR4	A014-C-040	Human	Colorectum	FAP	2.54e-04	-2.79e-01	-0.1184
65979	PHACTR4	A002-C-201	Human	Colorectum	FAP	1.56e-13	-2.87e-01	0.0324
65979	PHACTR4	A002-C-203	Human	Colorectum	FAP	4.03e-06	-1.94e-01	0.2786
65979	PHACTR4	A001-C-119	Human	Colorectum	FAP	4.56e-08	-2.13e-01	-0.1557
65979	PHACTR4	A001-C-108	Human	Colorectum	FAP	2.37e-19	-3.79e-01	-0.0272
65979	PHACTR4	A002-C-205	Human	Colorectum	FAP	2.47e-28	-3.72e-01	-0.1236

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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
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:00016679	Cervix	CC	ameboidal-type cell migration	110/2311	475/18723	2.66e-11	6.36e-09	110
GO:00072656	Cervix	CC	Ras protein signal transduction	79/2311	337/18723	9.49e-09	7.77e-07	79
GO:00072295	Cervix	CC	integrin-mediated signaling pathway	34/2311	107/18723	1.01e-07	5.25e-06	34
GO:00020111	Cervix	CC	morphogenesis of an epithelial sheet	21/2311	57/18723	1.91e-06	5.97e-05	21
GO:00072666	Cervix	CC	Rho protein signal transduction	35/2311	137/18723	1.77e-05	3.33e-04	35
GO:00488634	Cervix	CC	stem cell differentiation	46/2311	206/18723	4.11e-05	6.36e-04	46
GO:00351487	Cervix	CC	tube formation	31/2311	148/18723	2.07e-03	1.51e-02	31
GO:00018417	Cervix	CC	neural tube formation	23/2311	102/18723	2.80e-03	1.87e-02	23
GO:00605626	Cervix	CC	epithelial tube morphogenesis	57/2311	325/18723	3.79e-03	2.41e-02	57
GO:00140206	Cervix	CC	primary neural tube formation	21/2311	94/18723	4.68e-03	2.82e-02	21
GO:00219156	Cervix	CC	neural tube development	30/2311	152/18723	6.00e-03	3.43e-02	30
GO:0150063	Cervix	CC	visual system development	63/2311	375/18723	6.58e-03	3.65e-02	63
GO:0001654	Cervix	CC	eye development	62/2311	371/18723	7.83e-03	4.13e-02	62
GO:00487624	Cervix	CC	mesenchymal cell differentiation	42/2311	236/18723	9.12e-03	4.60e-02	42
GO:0048880	Cervix	CC	sensory system development	63/2311	381/18723	9.29e-03	4.66e-02	63
GO:00018435	Cervix	CC	neural tube closure	19/2311	88/18723	1.01e-02	4.91e-02	19
GO:0007265	Colorectum	AD	Ras protein signal transduction	104/3918	337/18723	1.01e-05	2.35e-04	104
GO:0001667	Colorectum	AD	ameboidal-type cell migration	137/3918	475/18723	2.17e-05	4.33e-04	137
GO:0060562	Colorectum	AD	epithelial tube morphogenesis	93/3918	325/18723	5.65e-04	6.00e-03	93
GO:0014020	Colorectum	AD	primary neural tube formation	33/3918	94/18723	1.02e-03	9.50e-03	33

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

PHACTR4

SNV

Missense_Mutation

novel

c.1060N>C

p.Ser354Pro

p.S354P

Q8IZ21

protein_coding

tolerated(0.16)

probably_damaging(0.997)

TCGA-A2-A04T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

PHACTR4

SNV

Missense_Mutation

rs543331485

c.1459N>A

p.Asp487Asn

p.D487N

Q8IZ21

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-A8-A08J-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

PHACTR4

SNV

Missense_Mutation

c.1182T>G

p.Ile394Met

p.I394M

Q8IZ21

protein_coding

tolerated_low_confidence(0.11)

benign(0.277)

TCGA-AN-A04D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PHACTR4

SNV

Missense_Mutation

c.2132N>A

p.Arg711His

p.R711H

Q8IZ21

protein_coding

deleterious(0)

possibly_damaging(0.489)

TCGA-C8-A12V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PHACTR4

SNV

Missense_Mutation

c.994G>A

p.Glu332Lys

p.E332K

Q8IZ21

protein_coding

tolerated(0.08)

benign(0.007)

TCGA-E2-A10C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

PHACTR4

SNV

Missense_Mutation

rs756268561

c.1358C>T

p.Ser453Leu

p.S453L

Q8IZ21

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PHACTR4

SNV

Missense_Mutation

novel

c.2131C>T

p.Arg711Cys

p.R711C

Q8IZ21

protein_coding

deleterious(0)

possibly_damaging(0.655)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PHACTR4

SNV

Missense_Mutation

novel

c.1423C>T

p.Leu475Phe

p.L475F

Q8IZ21

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-C5-A902-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PHACTR4

SNV

Missense_Mutation

novel

c.565C>T

p.His189Tyr

p.H189Y

Q8IZ21

protein_coding

tolerated(0.37)

benign(0.003)

TCGA-DS-A1OA-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

carboplatin

PHACTR4

SNV

Missense_Mutation

novel

c.2015N>C

p.Lys672Thr

p.K672T

Q8IZ21

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AA-3984-01

Colorectum

colon adenocarcinoma

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

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