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: ARNT

Gene summary for ARNT

Gene summary.

Gene information	Species	Human
	Gene symbol	ARNT
	Gene ID	405
	Gene name	aryl hydrocarbon receptor nuclear translocator
	Gene Alias	HIF-1-beta
	Cytomap	1q21.3
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	A8K6P0

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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
405	ARNT	LZE4T	Human	Esophagus	ESCC	2.83e-09	2.88e-01	0.0811
405	ARNT	LZE5T	Human	Esophagus	ESCC	8.14e-07	2.88e-01	0.0514
405	ARNT	LZE7T	Human	Esophagus	ESCC	4.11e-05	3.03e-01	0.0667
405	ARNT	LZE8T	Human	Esophagus	ESCC	2.93e-02	7.32e-02	0.067
405	ARNT	LZE20T	Human	Esophagus	ESCC	3.61e-03	1.49e-01	0.0662
405	ARNT	LZE22T	Human	Esophagus	ESCC	1.19e-05	3.41e-01	0.068
405	ARNT	LZE24T	Human	Esophagus	ESCC	8.17e-17	2.11e-01	0.0596
405	ARNT	P1T-E	Human	Esophagus	ESCC	1.51e-02	1.55e-01	0.0875
405	ARNT	P2T-E	Human	Esophagus	ESCC	3.24e-12	2.25e-01	0.1177
405	ARNT	P4T-E	Human	Esophagus	ESCC	4.41e-09	1.81e-01	0.1323
405	ARNT	P5T-E	Human	Esophagus	ESCC	1.50e-07	2.04e-01	0.1327
405	ARNT	P8T-E	Human	Esophagus	ESCC	1.56e-10	2.69e-01	0.0889
405	ARNT	P9T-E	Human	Esophagus	ESCC	1.49e-09	1.99e-01	0.1131
405	ARNT	P10T-E	Human	Esophagus	ESCC	1.82e-08	1.22e-01	0.116
405	ARNT	P11T-E	Human	Esophagus	ESCC	2.23e-07	3.67e-01	0.1426
405	ARNT	P12T-E	Human	Esophagus	ESCC	1.67e-06	2.01e-01	0.1122
405	ARNT	P15T-E	Human	Esophagus	ESCC	1.79e-22	4.33e-01	0.1149
405	ARNT	P16T-E	Human	Esophagus	ESCC	1.76e-14	1.83e-01	0.1153
405	ARNT	P17T-E	Human	Esophagus	ESCC	8.03e-05	2.96e-01	0.1278
405	ARNT	P19T-E	Human	Esophagus	ESCC	3.14e-05	3.57e-01	0.1662

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias

∗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:00485118	Cervix	CC	rhythmic process	65/2311	298/18723	2.79e-06	8.04e-05	65
GO:00076238	Cervix	CC	circadian rhythm	46/2311	210/18723	6.76e-05	9.60e-04	46
GO:0006091110	Esophagus	ESCC	generation of precursor metabolites and energy	331/8552	490/18723	3.86e-23	8.45e-21	331
GO:0009896111	Esophagus	ESCC	positive regulation of catabolic process	332/8552	492/18723	4.36e-23	9.22e-21	332
GO:0006979111	Esophagus	ESCC	response to oxidative stress	303/8552	446/18723	7.15e-22	1.30e-19	303
GO:0031331111	Esophagus	ESCC	positive regulation of cellular catabolic process	292/8552	427/18723	8.67e-22	1.53e-19	292
GO:1903320111	Esophagus	ESCC	regulation of protein modification by small protein conjugation or removal	181/8552	242/18723	1.80e-20	2.60e-18	181
GO:001820514	Esophagus	ESCC	peptidyl-lysine modification	259/8552	376/18723	3.90e-20	5.26e-18	259
GO:0062197111	Esophagus	ESCC	cellular response to chemical stress	234/8552	337/18723	5.37e-19	5.97e-17	234
GO:000170119	Esophagus	ESCC	in utero embryonic development	243/8552	367/18723	1.00e-15	6.86e-14	243
GO:0034599111	Esophagus	ESCC	cellular response to oxidative stress	197/8552	288/18723	3.76e-15	2.15e-13	197
GO:0046034111	Esophagus	ESCC	ATP metabolic process	189/8552	277/18723	1.99e-14	1.04e-12	189
GO:0070482111	Esophagus	ESCC	response to oxygen levels	218/8552	347/18723	6.91e-11	2.17e-09	218
GO:0043618111	Esophagus	ESCC	regulation of transcription from RNA polymerase II promoter in response to stress	42/8552	47/18723	3.91e-10	1.05e-08	42
GO:190332216	Esophagus	ESCC	positive regulation of protein modification by small protein conjugation or removal	99/8552	138/18723	4.39e-10	1.16e-08	99
GO:0043620111	Esophagus	ESCC	regulation of DNA-templated transcription in response to stress	46/8552	53/18723	5.17e-10	1.33e-08	46
GO:0036293111	Esophagus	ESCC	response to decreased oxygen levels	201/8552	322/18723	8.37e-10	2.04e-08	201
GO:0030522110	Esophagus	ESCC	intracellular receptor signaling pathway	170/8552	265/18723	8.58e-10	2.09e-08	170
GO:0030099111	Esophagus	ESCC	myeloid cell differentiation	232/8552	381/18723	1.22e-09	2.90e-08	232
GO:0001666111	Esophagus	ESCC	response to hypoxia	192/8552	307/18723	1.59e-09	3.69e-08	192

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05208211	Esophagus	ESCC	Chemical carcinogenesis - reactive oxygen species	168/4205	223/8465	1.83e-15	6.81e-14	3.49e-14	168
hsa0521118	Esophagus	ESCC	Renal cell carcinoma	51/4205	69/8465	3.29e-05	1.53e-04	7.83e-05	51
hsa0406629	Esophagus	ESCC	HIF-1 signaling pathway	75/4205	109/8465	3.66e-05	1.68e-04	8.60e-05	75
hsa05208310	Esophagus	ESCC	Chemical carcinogenesis - reactive oxygen species	168/4205	223/8465	1.83e-15	6.81e-14	3.49e-14	168
hsa0521119	Esophagus	ESCC	Renal cell carcinoma	51/4205	69/8465	3.29e-05	1.53e-04	7.83e-05	51
hsa04066113	Esophagus	ESCC	HIF-1 signaling pathway	75/4205	109/8465	3.66e-05	1.68e-04	8.60e-05	75

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
ARNT	GOB	Colorectum	CRC	SGSM3,TNFAIP8,ZG16, etc.	3.07e-02
ARNT	IMGOB	Colorectum	FAP	SGSM3,TNFAIP8,ZG16, etc.	2.13e-01
ARNT	PLA	Lung	AIS	IGHA1,SELENOM,AP000787.1, etc.	1.22e-01
ARNT	CD8TEREX	Lung	MIAC	FYCO1,DENND2C,C11orf80, etc.	3.70e-02
ARNT	COR	Oral cavity	LP	TBC1D12,APBB1,DGKD, etc.	2.28e-01
ARNT	GRA	Oral cavity	LP	TBC1D12,APBB1,DGKD, etc.	2.90e-01
ARNT	GRA	Oral cavity	OSCC	TBC1D12,APBB1,DGKD, etc.	1.35e-01
ARNT	MSC.PVA	Skin	ADJ	FEM1B,MT-ND6,AC092683.1, etc.	1.48e-02
ARNT	MSC.PVA	Skin	AK	FEM1B,MT-ND6,AC092683.1, etc.	1.11e-16
ARNT	ADIPO	Skin	SCCIS	FEM1B,MT-ND6,AC092683.1, etc.	0.00e+00

∗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

ARNT

SNV

Missense_Mutation

rs777162532

c.593N>C

p.Asn198Thr

p.N198T

P27540

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A2-A1G0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

ARNT

SNV

Missense_Mutation

c.2033N>T

p.Ser678Phe

p.S678F

P27540

protein_coding

tolerated_low_confidence(0.23)

benign(0.122)

TCGA-A8-A092-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

ARNT

SNV

Missense_Mutation

c.1106N>C

p.Ile369Thr

p.I369T

P27540

protein_coding

tolerated(0.9)

benign(0)

TCGA-A8-A092-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

ARNT

SNV

Missense_Mutation

c.2281N>C

p.Glu761Gln

p.E761Q

P27540

protein_coding

deleterious_low_confidence(0)

benign(0.26)

TCGA-AN-A0XW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

ARNT

SNV

Missense_Mutation

rs777162532

c.593N>C

p.Asn198Thr

p.N198T

P27540

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AO-A1KT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

fluorouracil

ARNT

SNV

Missense_Mutation

rs777162532

c.593N>C

p.Asn198Thr

p.N198T

P27540

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AQ-A1H3-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

ARNT

SNV

Missense_Mutation

rs777162532

c.593N>C

p.Asn198Thr

p.N198T

P27540

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-BH-A1EX-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ARNT

SNV

Missense_Mutation

rs777162532

c.593N>C

p.Asn198Thr

p.N198T

P27540

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-BH-A1F2-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

ARNT

SNV

Missense_Mutation

novel

c.1427N>A

p.Ser476Tyr

p.S476Y

P27540

protein_coding

deleterious(0)

possibly_damaging(0.73)

TCGA-C8-A8HP-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

ARNT

SNV

Missense_Mutation

c.1403N>A

p.Ser468Asn

p.S468N

P27540

protein_coding

tolerated(0.21)

benign(0)

TCGA-D8-A143-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

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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
405	ARNT	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR		HYDROCORTISONE	HYDROCORTISONE	10048155
405	ARNT	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR		TCDD		9787404,11026553,9579024,14687977
405	ARNT	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR		FUROSPONGOLIDE	FUROSPONGOLIDE	18989978
405	ARNT	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR		PROTEASOME INHIBITOR		10409767
405	ARNT	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR		EPICATECHIN GALLATE	EPICATECHIN GALLATE	15620252

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