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: PFN2

Gene summary for PFN2

Gene summary.

Gene information	Species	Human
	Gene symbol	PFN2
	Gene ID	5217
	Gene name	profilin 2
	Gene Alias	D3S1319E
	Cytomap	3q25.1
	Gene Type	protein-coding
	GO ID	GO:0001667
	UniProtAcc	P35080

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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
5217	PFN2	GSM4909281	Human	Breast	IDC	9.42e-56	9.63e-01	0.21
5217	PFN2	GSM4909282	Human	Breast	IDC	2.15e-13	4.39e-01	-0.0288
5217	PFN2	GSM4909285	Human	Breast	IDC	1.32e-05	2.38e-01	0.21
5217	PFN2	GSM4909286	Human	Breast	IDC	1.79e-06	1.83e-01	0.1081
5217	PFN2	GSM4909287	Human	Breast	IDC	3.29e-08	4.05e-01	0.2057
5217	PFN2	GSM4909289	Human	Breast	IDC	4.59e-04	5.16e-01	0.1064
5217	PFN2	GSM4909291	Human	Breast	IDC	1.44e-06	-2.72e-01	0.1753
5217	PFN2	GSM4909295	Human	Breast	IDC	2.50e-03	3.71e-01	0.0898
5217	PFN2	GSM4909296	Human	Breast	IDC	2.86e-06	-2.55e-01	0.1524
5217	PFN2	GSM4909304	Human	Breast	IDC	1.06e-02	2.08e-01	0.1636
5217	PFN2	GSM4909305	Human	Breast	IDC	3.57e-03	2.97e-01	0.0436
5217	PFN2	GSM4909308	Human	Breast	IDC	2.64e-04	-2.42e-01	0.158
5217	PFN2	GSM4909311	Human	Breast	IDC	1.74e-06	-1.94e-01	0.1534
5217	PFN2	GSM4909312	Human	Breast	IDC	3.21e-03	-1.34e-01	0.1552
5217	PFN2	GSM4909316	Human	Breast	IDC	2.39e-03	2.75e-01	0.21
5217	PFN2	GSM4909319	Human	Breast	IDC	3.58e-13	-1.70e-01	0.1563
5217	PFN2	GSM4909321	Human	Breast	IDC	2.08e-07	1.78e-01	0.1559
5217	PFN2	M2	Human	Breast	IDC	7.10e-12	7.63e-01	0.21
5217	PFN2	NCCBC14	Human	Breast	DCIS	2.64e-02	3.05e-02	0.2021
5217	PFN2	NCCBC5	Human	Breast	DCIS	1.04e-05	-2.18e-01	0.2046

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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
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
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
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

∗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:003164714	Breast	IDC	regulation of protein stability	50/1434	298/18723	1.14e-07	6.57e-06	50
GO:005082114	Breast	IDC	protein stabilization	35/1434	191/18723	1.12e-06	5.04e-05	35
GO:190290514	Breast	IDC	positive regulation of supramolecular fiber organization	37/1434	209/18723	1.33e-06	5.75e-05	37
GO:004325414	Breast	IDC	regulation of protein-containing complex assembly	61/1434	428/18723	1.77e-06	7.31e-05	61
GO:003133414	Breast	IDC	positive regulation of protein-containing complex assembly	40/1434	237/18723	1.77e-06	7.31e-05	40
GO:003297014	Breast	IDC	regulation of actin filament-based process	56/1434	397/18723	6.37e-06	1.99e-04	56
GO:000166714	Breast	IDC	ameboidal-type cell migration	64/1434	475/18723	6.65e-06	2.05e-04	64
GO:190290314	Breast	IDC	regulation of supramolecular fiber organization	54/1434	383/18723	9.40e-06	2.66e-04	54
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: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:005149214	Breast	IDC	regulation of stress fiber assembly	18/1434	91/18723	1.60e-04	2.76e-03	18
GO:00512712	Breast	IDC	negative regulation of cellular component movement	48/1434	367/18723	1.88e-04	3.12e-03	48
GO:000701514	Breast	IDC	actin filament organization	55/1434	442/18723	2.45e-04	3.84e-03	55
GO:20001462	Breast	IDC	negative regulation of cell motility	46/1434	359/18723	4.01e-04	5.60e-03	46

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
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
hsa0513154	Breast	DCIS	Shigellosis	46/846	247/8465	2.06e-05	2.38e-04	1.75e-04	46
hsa0481033	Breast	DCIS	Regulation of actin cytoskeleton	35/846	229/8465	6.89e-03	3.37e-02	2.48e-02	35
hsa05014	Colorectum	AD	Amyotrophic lateral sclerosis	164/2092	364/8465	4.28e-18	1.27e-16	8.09e-17	164
hsa05131	Colorectum	AD	Shigellosis	109/2092	247/8465	1.09e-11	2.44e-10	1.55e-10	109
hsa05132	Colorectum	AD	Salmonella infection	102/2092	249/8465	7.65e-09	1.28e-07	8.17e-08	102
hsa04015	Colorectum	AD	Rap1 signaling pathway	71/2092	210/8465	1.72e-03	9.68e-03	6.18e-03	71

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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

PFN2

SNV

Missense_Mutation

c.394G>C

p.Ala132Pro

p.A132P

P35080

protein_coding

deleterious(0.02)

probably_damaging(0.93)

TCGA-AN-A0XU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PFN2

SNV

Missense_Mutation

novel

c.393G>T

p.Met131Ile

p.M131I

P35080

protein_coding

deleterious(0.04)

benign(0.05)

TCGA-AN-A0XU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PFN2

insertion

Nonsense_Mutation

novel

c.228_229insCAGCTTTATTAAACTTAAAAGTCTCTTAAACTG

p.Asp76_Ser77insGlnLeuTyrTerThrTerLysSerLeuLysLeu

p.D76_S77insQLY*T*KSLKL

P35080

protein_coding

TCGA-A2-A0T2-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

xeloda

PFN2

SNV

Missense_Mutation

c.202G>A

p.Ala68Thr

p.A68T

P35080

protein_coding

deleterious(0.03)

benign(0.056)

TCGA-AA-3712-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Unknown

PFN2

SNV

Missense_Mutation

c.203N>T

p.Ala68Val

p.A68V

P35080

protein_coding

deleterious(0)

benign(0.056)

TCGA-CM-5861-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

PFN2

SNV

Missense_Mutation

novel

c.197N>G

p.Leu66Arg

p.L66R

P35080

protein_coding

deleterious(0)

probably_damaging(0.953)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

PFN2

SNV

Missense_Mutation

c.394N>A

p.Ala132Thr

p.A132T

P35080

protein_coding

tolerated(0.1)

benign(0.185)

TCGA-AJ-A3BH-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

I/II

Unknown

PFN2

SNV

Missense_Mutation

novel

c.151A>T

p.Ile51Phe

p.I51F

P35080

protein_coding

deleterious(0)

possibly_damaging(0.544)

TCGA-EC-A24G-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

PFN2

SNV

Missense_Mutation

novel

c.196N>G

p.Leu66Val

p.L66V

P35080

protein_coding

tolerated(0.19)

benign(0.097)

TCGA-P3-A5Q5-01

Oral cavity

head & neck squamous cell carcinoma

Male

<65

I/II

Unknown

PFN2

SNV

Missense_Mutation

rs763130284

c.367N>A

p.Gly123Arg

p.G123R

P35080

protein_coding

tolerated(0.53)

benign(0.005)

TCGA-EJ-7782-01

Prostate

prostate adenocarcinoma

Male

>=65

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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