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: PDGFRA

Gene summary for PDGFRA

Gene summary.

Gene information	Species	Human
	Gene symbol	PDGFRA
	Gene ID	5156
	Gene name	platelet derived growth factor receptor alpha
	Gene Alias	CD140A
	Cytomap	4q12
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P16234

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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
5156	PDGFRA	male-WTA	Human	Thyroid	PTC	2.99e-03	4.90e-02	0.1037
5156	PDGFRA	ATC12	Human	Thyroid	ATC	1.59e-67	1.44e+00	0.34
5156	PDGFRA	ATC13	Human	Thyroid	ATC	1.03e-63	1.45e+00	0.34
5156	PDGFRA	ATC3	Human	Thyroid	ATC	6.43e-04	3.19e-01	0.338
5156	PDGFRA	ATC4	Human	Thyroid	ATC	1.30e-83	1.61e+00	0.34
5156	PDGFRA	ATC5	Human	Thyroid	ATC	2.03e-80	1.53e+00	0.34

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:0006979113	Thyroid	PTC	response to oxidative stress	234/5968	446/18723	6.97e-20	9.77e-18	234
GO:0062197113	Thyroid	PTC	cellular response to chemical stress	180/5968	337/18723	1.36e-16	1.16e-14	180
GO:0032956113	Thyroid	PTC	regulation of actin cytoskeleton organization	182/5968	358/18723	4.64e-14	2.79e-12	182
GO:0032970113	Thyroid	PTC	regulation of actin filament-based process	197/5968	397/18723	8.91e-14	4.89e-12	197
GO:0034599113	Thyroid	PTC	cellular response to oxidative stress	151/5968	288/18723	2.82e-13	1.43e-11	151
GO:0000302113	Thyroid	PTC	response to reactive oxygen species	121/5968	222/18723	2.10e-12	9.26e-11	121
GO:0001701111	Thyroid	PTC	in utero embryonic development	175/5968	367/18723	1.40e-10	4.73e-09	175
GO:0042060112	Thyroid	PTC	wound healing	190/5968	422/18723	7.72e-09	1.92e-07	190
GO:0048732113	Thyroid	PTC	gland development	193/5968	436/18723	2.88e-08	6.42e-07	193
GO:0034614112	Thyroid	PTC	cellular response to reactive oxygen species	82/5968	155/18723	4.32e-08	9.27e-07	82
GO:004677716	Thyroid	PTC	protein autophosphorylation	110/5968	227/18723	1.25e-07	2.44e-06	110
GO:003153220	Thyroid	PTC	actin cytoskeleton reorganization	60/5968	107/18723	1.91e-07	3.51e-06	60
GO:0033674111	Thyroid	PTC	positive regulation of kinase activity	201/5968	467/18723	1.95e-07	3.54e-06	201
GO:000182215	Thyroid	PTC	kidney development	133/5968	293/18723	7.57e-07	1.18e-05	133
GO:000165517	Thyroid	PTC	urogenital system development	149/5968	338/18723	1.41e-06	2.01e-05	149
GO:007200114	Thyroid	PTC	renal system development	135/5968	302/18723	1.76e-06	2.43e-05	135
GO:000110119	Thyroid	PTC	response to acid chemical	69/5968	135/18723	2.55e-06	3.34e-05	69
GO:0048511111	Thyroid	PTC	rhythmic process	131/5968	298/18723	7.06e-06	8.33e-05	131
GO:00480089	Thyroid	PTC	platelet-derived growth factor receptor signaling pathway	34/5968	56/18723	8.20e-06	9.42e-05	34
GO:0031032110	Thyroid	PTC	actomyosin structure organization	91/5968	196/18723	1.35e-05	1.45e-04	91

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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
PDGFA	PDGFRA	PDGFA_PDGFRA	PDGF	Breast	ADJ
PDGFB	PDGFRA	PDGFB_PDGFRA	PDGF	Breast	ADJ
PDGFA	PDGFRA	PDGFA_PDGFRA	PDGF	Breast	DCIS
PDGFB	PDGFRA	PDGFB_PDGFRA	PDGF	Breast	DCIS
PDGFA	PDGFRA	PDGFA_PDGFRA	PDGF	Breast	Healthy
PDGFA	PDGFRA	PDGFA_PDGFRA	PDGF	Breast	IDC
PDGFC	PDGFRA	PDGFC_PDGFRA	PDGF	Breast	IDC
PDGFA	PDGFRA	PDGFA_PDGFRA	PDGF	Cervix	ADJ
PDGFA	PDGFRA	PDGFA_PDGFRA	PDGF	Cervix	CC
PDGFC	PDGFRA	PDGFC_PDGFRA	PDGF	Cervix	CC
PDGFA	PDGFRA	PDGFA_PDGFRA	PDGF	Cervix	Precancer
PDGFC	PDGFRA	PDGFC_PDGFRA	PDGF	Cervix	Precancer
PDGFB	PDGFRA	PDGFB_PDGFRA	PDGF	CRC	AD
PDGFC	PDGFRA	PDGFC_PDGFRA	PDGF	CRC	AD
PDGFC	PDGFRA	PDGFC_PDGFRA	PDGF	CRC	ADJ
PDGFA	PDGFRA	PDGFA_PDGFRA	PDGF	CRC	CRC
PDGFC	PDGFRA	PDGFC_PDGFRA	PDGF	CRC	CRC
PDGFA	PDGFRA	PDGFA_PDGFRA	PDGF	CRC	MSS
PDGFB	PDGFRA	PDGFB_PDGFRA	PDGF	CRC	MSS
PDGFA	PDGFRA	PDGFA_PDGFRA	PDGF	Endometrium	ADJ

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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

PDGFRA

SNV

Missense_Mutation

c.2942G>C

p.Arg981Pro

p.R981P

P16234

protein_coding

deleterious(0.03)

possibly_damaging(0.862)

TCGA-A2-A0T0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

PDGFRA

SNV

Missense_Mutation

c.2953N>A

p.Asp985Asn

p.D985N

P16234

protein_coding

tolerated(0.27)

benign(0.318)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PDGFRA

SNV

Missense_Mutation

c.1711N>A

p.Glu571Lys

p.E571K

P16234

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-AO-A12D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

PDGFRA

SNV

Missense_Mutation

rs763325080

c.2465N>A

p.Arg822His

p.R822H

P16234

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AR-A1AV-01

Breast

breast invasive carcinoma

Male

>=65

I/II

Chemotherapy

cytoxan

PDGFRA

SNV

Missense_Mutation

rs767697835

c.3223N>A

p.Asp1075Asn

p.D1075N

P16234

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.631)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PDGFRA

SNV

Missense_Mutation

c.1666G>A

p.Glu556Lys

p.E556K

P16234

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PDGFRA

insertion

Frame_Shift_Ins

novel

c.905_906insATCTCCATCTCTTAGAATCTTTCTCCACCATCTCTCCTTTCTAG

p.Met302IlefsTer51

p.M302Ifs*51

P16234

protein_coding

TCGA-A2-A0CX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

PDGFRA

insertion

Nonsense_Mutation

novel

c.2875_2876insCCATGTTCAGCTAATTTTTGTATTTTT

p.Lys959delinsThrMetPheSerTerPheLeuTyrPheTer

p.K959delinsTMFS*FLYF*

P16234

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

PDGFRA

insertion

Frame_Shift_Ins

novel

c.2035_2036insTG

p.Tyr679LeufsTer17

p.Y679Lfs*17

P16234

protein_coding

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

PDGFRA

insertion

Nonsense_Mutation

novel

c.2036_2037insGAACAGGAAGT

p.Tyr679Ter

p.Y679*

P16234

protein_coding

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

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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
5156	PDGFRA	TYROSINE KINASE, KINASE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUG RESISTANCE		IMATINIB	IMATINIB	15928335,15685537,22718859,16638875,15146165,12949711,26130666,25157968,24132921,14645423,16954519,18794084,22745105
5156	PDGFRA	TYROSINE KINASE, KINASE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUG RESISTANCE		DASATINIB	DASATINIB	15928335,15685537,22718859,16638875,15146165,12949711,26130666,25157968,14645423,16954519,18794084,22745105
5156	PDGFRA	TYROSINE KINASE, KINASE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUG RESISTANCE		VANDETANIB	VANDETANIB
5156	PDGFRA	TYROSINE KINASE, KINASE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUG RESISTANCE	inhibitor	363894199
5156	PDGFRA	TYROSINE KINASE, KINASE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUG RESISTANCE		CP-868596	CRENOLANIB
5156	PDGFRA	TYROSINE KINASE, KINASE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUG RESISTANCE	inhibitor	249565576	ENMD-2076
5156	PDGFRA	TYROSINE KINASE, KINASE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUG RESISTANCE		LINIFANIB	LINIFANIB
5156	PDGFRA	TYROSINE KINASE, KINASE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUG RESISTANCE	antibody	OLARATUMAB	OLARATUMAB
5156	PDGFRA	TYROSINE KINASE, KINASE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUG RESISTANCE	inhibitor	178102559	NINTEDANIB
5156	PDGFRA	TYROSINE KINASE, KINASE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUG RESISTANCE		CYC-116	CYC-116

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