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: AR

Gene summary for AR

Gene summary.

Gene information	Species	Human
	Gene symbol	AR
	Gene ID	367
	Gene name	androgen receptor
	Gene Alias	AIS
	Cytomap	Xq12
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P10275

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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
367	AR	GSM4909282	Human	Breast	IDC	8.07e-06	-1.87e-01	-0.0288
367	AR	GSM4909285	Human	Breast	IDC	8.07e-06	-1.82e-01	0.21
367	AR	GSM4909286	Human	Breast	IDC	1.72e-05	-1.87e-01	0.1081
367	AR	GSM4909287	Human	Breast	IDC	2.91e-04	-1.82e-01	0.2057
367	AR	GSM4909290	Human	Breast	IDC	3.95e-05	3.05e-01	0.2096
367	AR	GSM4909291	Human	Breast	IDC	8.28e-03	-1.87e-01	0.1753
367	AR	GSM4909293	Human	Breast	IDC	2.02e-73	1.07e+00	0.1581
367	AR	GSM4909298	Human	Breast	IDC	4.69e-05	1.52e-01	0.1551
367	AR	GSM4909301	Human	Breast	IDC	2.32e-27	7.04e-01	0.1577
367	AR	GSM4909303	Human	Breast	IDC	1.07e-07	5.92e-01	0.0438
367	AR	GSM4909306	Human	Breast	IDC	1.70e-27	6.27e-01	0.1564
367	AR	GSM4909307	Human	Breast	IDC	5.11e-04	2.83e-01	0.1569
367	AR	GSM4909308	Human	Breast	IDC	3.47e-09	3.55e-01	0.158
367	AR	GSM4909309	Human	Breast	IDC	1.10e-02	-1.66e-01	0.0483
367	AR	GSM4909311	Human	Breast	IDC	9.12e-06	-8.10e-02	0.1534
367	AR	GSM4909313	Human	Breast	IDC	2.86e-05	3.06e-01	0.0391
367	AR	GSM4909319	Human	Breast	IDC	5.65e-03	-1.17e-01	0.1563
367	AR	M5	Human	Breast	IDC	2.93e-07	7.39e-01	0.1598
367	AR	P1	Human	Breast	IDC	2.51e-02	9.14e-02	0.1527
367	AR	NAFLD1	Human	Liver	NAFLD	8.87e-12	1.11e+00	-0.04

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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
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease
Prostate		BPH: Benign Prostatic Hyperplasia

∗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:00460349	Breast	Precancer	ATP metabolic process	82/1080	277/18723	1.94e-36	5.19e-33	82
GO:00061199	Breast	Precancer	oxidative phosphorylation	53/1080	141/18723	1.15e-29	2.04e-26	53
GO:00090608	Breast	Precancer	aerobic respiration	58/1080	189/18723	5.69e-27	7.62e-24	58
GO:00060918	Breast	Precancer	generation of precursor metabolites and energy	94/1080	490/18723	1.54e-25	1.64e-22	94
GO:00453338	Breast	Precancer	cellular respiration	59/1080	230/18723	5.97e-23	5.32e-20	59
GO:00159808	Breast	Precancer	energy derivation by oxidation of organic compounds	70/1080	318/18723	8.33e-23	6.37e-20	70
GO:00196468	Breast	Precancer	aerobic electron transport chain	34/1080	87/18723	3.95e-20	2.64e-17	34
GO:00427738	Breast	Precancer	ATP synthesis coupled electron transport	35/1080	95/18723	1.08e-19	5.76e-17	35
GO:00427758	Breast	Precancer	mitochondrial ATP synthesis coupled electron transport	35/1080	95/18723	1.08e-19	5.76e-17	35
GO:00971939	Breast	Precancer	intrinsic apoptotic signaling pathway	59/1080	288/18723	8.07e-18	3.60e-15	59
GO:20012339	Breast	Precancer	regulation of apoptotic signaling pathway	65/1080	356/18723	7.70e-17	3.17e-14	65
GO:00229048	Breast	Precancer	respiratory electron transport chain	35/1080	114/18723	8.51e-17	3.26e-14	35
GO:20012429	Breast	Precancer	regulation of intrinsic apoptotic signaling pathway	41/1080	164/18723	6.48e-16	2.31e-13	41
GO:00229008	Breast	Precancer	electron transport chain	42/1080	175/18723	1.37e-15	4.59e-13	42
GO:19026008	Breast	Precancer	proton transmembrane transport	39/1080	157/18723	4.18e-15	1.18e-12	39
GO:00069799	Breast	Precancer	response to oxidative stress	70/1080	446/18723	1.59e-14	4.26e-12	70
GO:00525479	Breast	Precancer	regulation of peptidase activity	71/1080	461/18723	2.72e-14	6.94e-12	71
GO:00525489	Breast	Precancer	regulation of endopeptidase activity	67/1080	432/18723	1.06e-13	2.36e-11	67
GO:00067547	Breast	Precancer	ATP biosynthetic process	21/1080	57/18723	2.31e-12	4.26e-10	21
GO:20001169	Breast	Precancer	regulation of cysteine-type endopeptidase activity	43/1080	235/18723	1.30e-11	1.83e-09	43

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa052159	Prostate	BPH	Prostate cancer	48/1718	97/8465	1.08e-10	1.87e-09	1.16e-09	48
hsa0521514	Prostate	BPH	Prostate cancer	48/1718	97/8465	1.08e-10	1.87e-09	1.16e-09	48

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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
GZMA	PARD3	GZMA_PARD3	PARs	Breast	ADJ
C3	C3AR1	C3_C3AR1	COMPLEMENT	Breast	DCIS
C3	C3AR1	C3_C3AR1	COMPLEMENT	Breast	Healthy
C3	C3AR1	C3_C3AR1	COMPLEMENT	Breast	IDC
C3	C3AR1	C3_C3AR1	COMPLEMENT	Cervix	ADJ
PRSS3	PARD3	PRSS3_PARD3	PARs	Cervix	CC
CTSG	PARD3	CTSG_PARD3	PARs	Cervix	CC
GZMA	PARD3	GZMA_PARD3	PARs	Cervix	CC
C3	C3AR1	C3_C3AR1	COMPLEMENT	Cervix	CC
C5	C5AR1	HC_C5AR1	COMPLEMENT	Cervix	CC
EDA	EDAR	EDA_EDAR	EDA	Cervix	CC
C3	C3AR1	C3_C3AR1	COMPLEMENT	Cervix	Precancer
PRSS3	PARD3	PRSS3_PARD3	PARs	CRC	AD
CTSG	PARD3	CTSG_PARD3	PARs	CRC	AD
GZMA	PARD3	GZMA_PARD3	PARs	CRC	AD
PRSS3	PARD3	PRSS3_PARD3	PARs	CRC	ADJ
CTSG	PARD3	CTSG_PARD3	PARs	CRC	ADJ
GZMA	PARD3	GZMA_PARD3	PARs	CRC	ADJ
PRSS3	PARD3	PRSS3_PARD3	PARs	CRC	CRC
PRSS3	PARD3	PRSS3_PARD3	PARs	CRC	Healthy

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
AR	STM	Breast	Healthy	XBP1,PIKFYVE,IL6ST, etc.	1.41e-01
AR	MLUM	Breast	Healthy	XBP1,PIKFYVE,IL6ST, etc.	3.44e-01
AR	CAF	Breast	Precancer	CDH1,TMTC2,MLPH, etc.	2.25e-01
AR	INCAF	Breast	Precancer	CDH1,TMTC2,MLPH, etc.	1.84e-01
AR	KER	Cervix	CC	MT-ND3,MT-ND1,SPARCL1, etc.	2.21e-02
AR	CT	Colorectum	ADJ	AR(+)	1.57e-01
AR	CLUB	Lung	AAH	PIGR,LCN2,KLK11, etc.	3.09e-01
AR	CLUB	Lung	ADJ	PIGR,LCN2,KLK11, etc.	4.33e-01
AR	CLUB	Lung	AIS	PIGR,LCN2,KLK11, etc.	1.07e-01
AR	CLUB	Lung	IAC	PIGR,LCN2,KLK11, etc.	2.95e-01

∗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

SNV

Missense_Mutation

c.2595N>A

p.Asp865Glu

p.D865E

P10275

protein_coding

deleterious(0)

probably_damaging(0.923)

TCGA-A1-A0SO-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

SNV

Missense_Mutation

c.1912N>A

p.Leu638Met

p.L638M

P10275

protein_coding

tolerated(0.07)

benign(0.316)

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

SNV

Missense_Mutation

novel

c.1082N>A

p.Ser361Asn

p.S361N

P10275

protein_coding

tolerated_low_confidence(0.27)

benign(0.015)

TCGA-AC-A8OP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SNV

Missense_Mutation

c.1681N>A

p.Leu561Met

p.L561M

P10275

protein_coding

deleterious(0.03)

probably_damaging(0.999)

TCGA-BH-A18L-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

SNV

Missense_Mutation

c.1703C>T

p.Ser568Phe

p.S568F

P10275

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-E9-A1R4-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

5-fluorouracil

SNV

Missense_Mutation

novel

c.2642N>A

p.Leu881Gln

p.L881Q

P10275

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-OL-A66K-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SNV

Missense_Mutation

novel

c.585N>T

p.Gln195His

p.Q195H

P10275

protein_coding

tolerated_low_confidence(0.13)

benign(0.005)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SNV

Missense_Mutation

novel

c.2718N>T

p.Lys906Asn

p.K906N

P10275

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SNV

Missense_Mutation

novel

c.967N>A

p.Glu323Lys

p.E323K

P10275

protein_coding

tolerated_low_confidence(0.11)

benign(0.265)

TCGA-C5-A1MN-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

SNV

Missense_Mutation

c.2462G>T

p.Gly821Val

p.G821V

P10275

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

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
367	AR	DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, DRUG RESISTANCE		FLUOCINOLONE ACETONIDE	FLUOCINOLONE ACETONIDE
367	AR	DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, DRUG RESISTANCE		4-CHLOROMERCURIBENZOIC ACID	4-CHLOROMERCURIBENZOIC ACID
367	AR	DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, DRUG RESISTANCE	agonist	CHEMBL2107067	TESTOSTERONE UNDECANOATE
367	AR	DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, DRUG RESISTANCE		DIDECYLDIMETHYLAMMONIUM CHLORIDE	DIDECYLDIMETHYLAMMONIUM CHLORIDE
367	AR	DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, DRUG RESISTANCE		QUININE SULFATE	QUININE SULFATE
367	AR	DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, DRUG RESISTANCE		NILUTAMIDE	NILUTAMIDE
367	AR	DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, DRUG RESISTANCE		RALOXIFENE HYDROCHLORIDE	RALOXIFENE HYDROCHLORIDE
367	AR	DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, DRUG RESISTANCE		ARN-509	APALUTAMIDE
367	AR	DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, DRUG RESISTANCE		CRUFOMATE	CRUFOMATE
367	AR	DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR, CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR, DRUG RESISTANCE		2-AMINOFLURENE	CHEMBL84472