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: AP1AR

Gene summary for AP1AR

Gene summary.

Gene information	Species	Human
	Gene symbol	AP1AR
	Gene ID	55435
	Gene name	adaptor related protein complex 1 associated regulatory protein
	Gene Alias	2C18
	Cytomap	4q25
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	A0A024RDI1

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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
55435	AP1AR	NAFLD1	Human	Liver	NAFLD	4.09e-05	3.59e-01	-0.04
55435	AP1AR	HCC1_Meng	Human	Liver	HCC	5.23e-33	1.08e-02	0.0246
55435	AP1AR	HCC2_Meng	Human	Liver	HCC	4.75e-23	9.23e-02	0.0107
55435	AP1AR	HCC2	Human	Liver	HCC	7.84e-20	4.49e+00	0.5341
55435	AP1AR	S015	Human	Liver	HCC	1.47e-03	2.49e-01	0.2375
55435	AP1AR	S027	Human	Liver	HCC	2.59e-04	4.76e-01	0.2446
55435	AP1AR	S028	Human	Liver	HCC	4.78e-17	6.30e-01	0.2503
55435	AP1AR	S029	Human	Liver	HCC	1.18e-08	4.35e-01	0.2581

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease

∗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:00481936	Liver	NAFLD	Golgi vesicle transport	66/1882	296/18723	3.66e-10	9.30e-08	66
GO:00068925	Liver	NAFLD	post-Golgi vesicle-mediated transport	31/1882	104/18723	1.70e-08	2.03e-06	31
GO:00226047	Liver	NAFLD	regulation of cell morphogenesis	62/1882	309/18723	8.35e-08	7.09e-06	62
GO:00108107	Liver	NAFLD	regulation of cell-substrate adhesion	47/1882	221/18723	5.30e-07	3.16e-05	47
GO:00070157	Liver	NAFLD	actin filament organization	78/1882	442/18723	5.44e-07	3.21e-05	78
GO:00315896	Liver	NAFLD	cell-substrate adhesion	65/1882	363/18723	2.84e-06	1.18e-04	65
GO:19029037	Liver	NAFLD	regulation of supramolecular fiber organization	66/1882	383/18723	8.97e-06	2.96e-04	66
GO:00107697	Liver	NAFLD	regulation of cell morphogenesis involved in differentiation	24/1882	96/18723	1.98e-05	5.62e-04	24
GO:19000247	Liver	NAFLD	regulation of substrate adhesion-dependent cell spreading	17/1882	57/18723	2.81e-05	7.46e-04	17
GO:00329707	Liver	NAFLD	regulation of actin filament-based process	66/1882	397/18723	2.92e-05	7.72e-04	66
GO:19029057	Liver	NAFLD	positive regulation of supramolecular fiber organization	40/1882	209/18723	4.88e-05	1.15e-03	40
GO:00329567	Liver	NAFLD	regulation of actin cytoskeleton organization	60/1882	358/18723	5.20e-05	1.20e-03	60
GO:00344467	Liver	NAFLD	substrate adhesion-dependent cell spreading	25/1882	108/18723	5.41e-05	1.23e-03	25
GO:00164825	Liver	NAFLD	cytosolic transport	34/1882	168/18723	5.52e-05	1.25e-03	34
GO:01100537	Liver	NAFLD	regulation of actin filament organization	49/1882	278/18723	6.88e-05	1.46e-03	49
GO:00432547	Liver	NAFLD	regulation of protein-containing complex assembly	66/1882	428/18723	2.83e-04	4.53e-03	66
GO:00512587	Liver	NAFLD	protein polymerization	49/1882	297/18723	3.54e-04	5.36e-03	49
GO:00431124	Liver	NAFLD	receptor metabolic process	31/1882	166/18723	5.10e-04	7.15e-03	31
GO:00343153	Liver	NAFLD	regulation of Arp2/3 complex-mediated actin nucleation	8/1882	21/18723	6.29e-04	8.21e-03	8
GO:00322717	Liver	NAFLD	regulation of protein polymerization	38/1882	233/18723	1.90e-03	1.93e-02	38

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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

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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

AP1AR

SNV

Missense_Mutation

rs746515200

c.905N>A

p.Arg302Gln

p.R302Q

Q63HQ0

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.99)

TCGA-D8-A1JG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

AP1AR

SNV

Missense_Mutation

rs562537794

c.340C>T

p.Arg114Cys

p.R114C

Q63HQ0

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-Q1-A5R2-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

AP1AR

SNV

Missense_Mutation

rs367798505

c.802N>A

p.Glu268Lys

p.E268K

Q63HQ0

protein_coding

deleterious(0.03)

benign(0.311)

TCGA-AA-3977-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

AP1AR

SNV

Missense_Mutation

rs754855886

c.463G>A

p.Glu155Lys

p.E155K

Q63HQ0

protein_coding

deleterious(0.02)

benign(0.311)

TCGA-AG-3878-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

AP1AR

SNV

Missense_Mutation

novel

c.728N>C

p.Lys243Thr

p.K243T

Q63HQ0

protein_coding

deleterious(0.03)

possibly_damaging(0.447)

TCGA-AJ-A3EK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

AP1AR

SNV

Missense_Mutation

rs746515200

c.905G>A

p.Arg302Gln

p.R302Q

Q63HQ0

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.99)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

AP1AR

SNV

Missense_Mutation

rs746050291

c.506N>A

p.Arg169Gln

p.R169Q

Q63HQ0

protein_coding

tolerated(0.11)

benign(0.127)

TCGA-AP-A056-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

AP1AR

SNV

Missense_Mutation

novel

c.488N>T

p.Ser163Leu

p.S163L

Q63HQ0

protein_coding

tolerated(0.19)

benign(0.001)

TCGA-AX-A1CE-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

AP1AR

SNV

Missense_Mutation

c.673N>T

p.Arg225Cys

p.R225C

Q63HQ0

protein_coding

deleterious(0)

benign(0.015)

TCGA-B5-A0JY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

AP1AR

SNV

Missense_Mutation

novel

c.514N>G

p.Arg172Gly

p.R172G

Q63HQ0

protein_coding

tolerated(0.11)

probably_damaging(0.99)

TCGA-DI-A1BU-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

paclitaxel

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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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