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: PFN1

Gene summary for PFN1

Gene summary.

Gene information	Species	Human
	Gene symbol	PFN1
	Gene ID	5216
	Gene name	profilin 1
	Gene Alias	ALS18
	Cytomap	17p13.2
	Gene Type	protein-coding
	GO ID	GO:0001667
	UniProtAcc	P07737

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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
5216	PFN1	GSM4909281	Human	Breast	IDC	1.34e-06	2.42e-01	0.21
5216	PFN1	GSM4909282	Human	Breast	IDC	2.68e-02	1.98e-01	-0.0288
5216	PFN1	GSM4909285	Human	Breast	IDC	1.13e-03	2.25e-01	0.21
5216	PFN1	GSM4909286	Human	Breast	IDC	4.52e-46	-6.45e-01	0.1081
5216	PFN1	GSM4909288	Human	Breast	IDC	1.43e-03	-4.62e-01	0.0988
5216	PFN1	GSM4909292	Human	Breast	IDC	1.10e-04	-8.23e-01	0.1236
5216	PFN1	GSM4909293	Human	Breast	IDC	4.09e-21	-3.77e-01	0.1581
5216	PFN1	GSM4909294	Human	Breast	IDC	3.40e-11	-5.08e-01	0.2022
5216	PFN1	GSM4909295	Human	Breast	IDC	1.03e-07	3.15e-01	0.0898
5216	PFN1	GSM4909296	Human	Breast	IDC	4.18e-05	2.11e-03	0.1524
5216	PFN1	GSM4909297	Human	Breast	IDC	1.37e-20	-2.39e-01	0.1517
5216	PFN1	GSM4909298	Human	Breast	IDC	1.09e-03	-1.17e-01	0.1551
5216	PFN1	GSM4909299	Human	Breast	IDC	2.69e-05	-1.93e-01	0.035
5216	PFN1	GSM4909301	Human	Breast	IDC	8.85e-38	4.08e-01	0.1577
5216	PFN1	GSM4909303	Human	Breast	IDC	2.04e-07	-5.90e-01	0.0438
5216	PFN1	GSM4909308	Human	Breast	IDC	2.83e-05	-1.08e-01	0.158
5216	PFN1	GSM4909311	Human	Breast	IDC	2.46e-49	-6.93e-01	0.1534
5216	PFN1	GSM4909312	Human	Breast	IDC	5.78e-04	-2.37e-01	0.1552
5216	PFN1	GSM4909317	Human	Breast	IDC	1.77e-19	-4.98e-01	0.1355
5216	PFN1	GSM4909319	Human	Breast	IDC	7.22e-65	-7.13e-01	0.1563

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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:001063112	Breast	IDC	epithelial cell migration	51/1434	357/18723	1.14e-05	3.08e-04	51
GO:009013212	Breast	IDC	epithelium migration	51/1434	360/18723	1.44e-05	3.70e-04	51
GO:009013012	Breast	IDC	tissue migration	51/1434	365/18723	2.11e-05	5.11e-04	51
GO:001063212	Breast	IDC	regulation of epithelial cell migration	43/1434	292/18723	2.61e-05	6.17e-04	43
GO:001063413	Breast	IDC	positive regulation of epithelial cell migration	30/1434	176/18723	2.76e-05	6.50e-04	30
GO:003227314	Breast	IDC	positive regulation of protein polymerization	25/1434	138/18723	4.46e-05	1.01e-03	25
GO:005149513	Breast	IDC	positive regulation of cytoskeleton organization	35/1434	226/18723	5.04e-05	1.09e-03	35
GO:003295614	Breast	IDC	regulation of actin cytoskeleton organization	48/1434	358/18723	1.03e-04	1.96e-03	48
GO:004346212	Breast	IDC	regulation of ATPase activity	12/1434	46/18723	1.31e-04	2.37e-03	12
GO:006056212	Breast	IDC	epithelial tube morphogenesis	44/1434	325/18723	1.58e-04	2.73e-03	44
GO:005149214	Breast	IDC	regulation of stress fiber assembly	18/1434	91/18723	1.60e-04	2.76e-03	18
GO:000701514	Breast	IDC	actin filament organization	55/1434	442/18723	2.45e-04	3.84e-03	55
GO:003003814	Breast	IDC	contractile actin filament bundle assembly	19/1434	106/18723	4.05e-04	5.60e-03	19
GO:004314914	Breast	IDC	stress fiber assembly	19/1434	106/18723	4.05e-04	5.60e-03	19
GO:011002014	Breast	IDC	regulation of actomyosin structure organization	18/1434	100/18723	5.40e-04	6.96e-03	18
GO:011005314	Breast	IDC	regulation of actin filament organization	37/1434	278/18723	7.01e-04	8.58e-03	37
GO:003223313	Breast	IDC	positive regulation of actin filament bundle assembly	13/1434	63/18723	8.33e-04	9.75e-03	13
GO:005101714	Breast	IDC	actin filament bundle assembly	24/1434	157/18723	8.73e-04	1.01e-02	24
GO:003514812	Breast	IDC	tube formation	23/1434	148/18723	8.79e-04	1.02e-02	23
GO:00322719	Breast	IDC	regulation of protein polymerization	32/1434	233/18723	9.19e-04	1.05e-02	32

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0501416	Breast	Precancer	Amyotrophic lateral sclerosis	98/684	364/8465	2.13e-28	8.41e-27	6.44e-27	98
hsa0513218	Breast	Precancer	Salmonella infection	49/684	249/8465	2.92e-09	6.15e-08	4.71e-08	49
hsa0513118	Breast	Precancer	Shigellosis	44/684	247/8465	3.91e-07	6.86e-06	5.26e-06	44
hsa0501417	Breast	Precancer	Amyotrophic lateral sclerosis	98/684	364/8465	2.13e-28	8.41e-27	6.44e-27	98
hsa0513219	Breast	Precancer	Salmonella infection	49/684	249/8465	2.92e-09	6.15e-08	4.71e-08	49
hsa0513119	Breast	Precancer	Shigellosis	44/684	247/8465	3.91e-07	6.86e-06	5.26e-06	44
hsa0501423	Breast	IDC	Amyotrophic lateral sclerosis	102/867	364/8465	1.29e-22	5.22e-21	3.91e-21	102
hsa0513224	Breast	IDC	Salmonella infection	55/867	249/8465	2.07e-08	4.49e-07	3.36e-07	55
hsa0513124	Breast	IDC	Shigellosis	47/867	247/8465	1.78e-05	2.00e-04	1.49e-04	47
hsa0481014	Breast	IDC	Regulation of actin cytoskeleton	36/867	229/8465	5.79e-03	3.13e-02	2.34e-02	36
hsa0501433	Breast	IDC	Amyotrophic lateral sclerosis	102/867	364/8465	1.29e-22	5.22e-21	3.91e-21	102
hsa0513234	Breast	IDC	Salmonella infection	55/867	249/8465	2.07e-08	4.49e-07	3.36e-07	55
hsa0513134	Breast	IDC	Shigellosis	47/867	247/8465	1.78e-05	2.00e-04	1.49e-04	47
hsa0481015	Breast	IDC	Regulation of actin cytoskeleton	36/867	229/8465	5.79e-03	3.13e-02	2.34e-02	36
hsa0501443	Breast	DCIS	Amyotrophic lateral sclerosis	101/846	364/8465	7.14e-23	2.88e-21	2.12e-21	101
hsa0513243	Breast	DCIS	Salmonella infection	55/846	249/8465	8.71e-09	1.87e-07	1.38e-07	55
hsa0513144	Breast	DCIS	Shigellosis	46/846	247/8465	2.06e-05	2.38e-04	1.75e-04	46
hsa0481023	Breast	DCIS	Regulation of actin cytoskeleton	35/846	229/8465	6.89e-03	3.37e-02	2.48e-02	35
hsa0501453	Breast	DCIS	Amyotrophic lateral sclerosis	101/846	364/8465	7.14e-23	2.88e-21	2.12e-21	101
hsa0513253	Breast	DCIS	Salmonella infection	55/846	249/8465	8.71e-09	1.87e-07	1.38e-07	55

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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

PFN1

SNV

Missense_Mutation

novel

c.25N>C

p.Asp9His

p.D9H

P07737

protein_coding

tolerated(0.08)

possibly_damaging(0.771)

TCGA-DG-A2KK-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

PFN1

SNV

Missense_Mutation

c.349N>C

p.Glu117Gln

p.E117Q

P07737

protein_coding

deleterious(0.01)

possibly_damaging(0.517)

TCGA-HM-A4S6-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

PFN1

SNV

Missense_Mutation

c.349G>A

p.Glu117Lys

p.E117K

P07737

protein_coding

tolerated(0.15)

benign(0.26)

TCGA-ZJ-AAXU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PFN1

SNV

Missense_Mutation

c.401A>T

p.His134Leu

p.H134L

P07737

protein_coding

tolerated(0.12)

benign(0.019)

TCGA-CK-4951-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

PFN1

SNV

Missense_Mutation

novel

c.197N>G

p.Leu66Arg

p.L66R

P07737

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PFN1

SNV

Missense_Mutation

novel

c.355N>A

p.Val119Ile

p.V119I

P07737

protein_coding

tolerated(0.13)

benign(0.001)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

PFN1

SNV

Missense_Mutation

novel

c.382N>G

p.Cys128Gly

p.C128G

P07737

protein_coding

deleterious(0)

benign(0.184)

TCGA-AX-A1CE-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

PFN1

SNV

Missense_Mutation

c.313N>G

p.Lys105Glu

p.K105E

P07737

protein_coding

deleterious(0.04)

benign(0.068)

TCGA-D1-A174-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PFN1

SNV

Missense_Mutation

novel

c.380N>G

p.Lys127Arg

p.K127R

P07737

protein_coding

deleterious(0.01)

benign(0.011)

TCGA-E6-A1LX-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PFN1

SNV

Missense_Mutation

novel

c.172N>C

p.Ser58Arg

p.S58R

P07737

protein_coding

tolerated(0.27)

benign(0.224)

TCGA-EY-A1GI-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

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