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: IL4R

Gene summary for IL4R

Gene summary.

Gene information	Species	Human
	Gene symbol	IL4R
	Gene ID	3566
	Gene name	interleukin 4 receptor
	Gene Alias	CD124
	Cytomap	16p12.1
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P24394

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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
3566	IL4R	HTA11_2487_2000001011	Human	Colorectum	SER	6.94e-04	3.52e-01	-0.1808
3566	IL4R	HTA11_1938_2000001011	Human	Colorectum	AD	4.52e-04	3.69e-01	-0.0811
3566	IL4R	HTA11_347_2000001011	Human	Colorectum	AD	3.79e-06	4.35e-01	-0.1954
3566	IL4R	HTA11_411_2000001011	Human	Colorectum	SER	4.79e-02	8.04e-01	-0.2602
3566	IL4R	HTA11_696_2000001011	Human	Colorectum	AD	2.20e-16	7.02e-01	-0.1464
3566	IL4R	HTA11_866_2000001011	Human	Colorectum	AD	9.17e-14	5.35e-01	-0.1001
3566	IL4R	HTA11_1391_2000001011	Human	Colorectum	AD	5.40e-04	4.98e-01	-0.059
3566	IL4R	HTA11_546_2000001011	Human	Colorectum	AD	4.59e-02	5.66e-01	-0.0842
3566	IL4R	A015-C-203	Human	Colorectum	FAP	3.30e-08	-2.53e-02	-0.1294
3566	IL4R	A001-C-108	Human	Colorectum	FAP	1.10e-02	-5.08e-02	-0.0272
3566	IL4R	A002-C-205	Human	Colorectum	FAP	1.60e-06	-1.07e-01	-0.1236
3566	IL4R	A015-C-006	Human	Colorectum	FAP	1.19e-04	-1.90e-01	-0.0994
3566	IL4R	A002-C-114	Human	Colorectum	FAP	1.54e-04	-2.28e-02	-0.1561
3566	IL4R	A015-C-104	Human	Colorectum	FAP	3.58e-07	-4.01e-02	-0.1899
3566	IL4R	A002-C-016	Human	Colorectum	FAP	8.07e-03	-1.20e-01	0.0521
3566	IL4R	A015-C-002	Human	Colorectum	FAP	2.69e-02	-6.17e-02	-0.0763
3566	IL4R	A002-C-116	Human	Colorectum	FAP	4.05e-06	-8.45e-02	-0.0452
3566	IL4R	A014-C-008	Human	Colorectum	FAP	2.82e-02	-1.63e-02	-0.191
3566	IL4R	A018-E-020	Human	Colorectum	FAP	1.83e-05	-1.13e-01	-0.2034
3566	IL4R	F034	Human	Colorectum	FAP	2.98e-04	-1.46e-01	-0.0665

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:0051656	Colorectum	AD	establishment of organelle localization	131/3918	390/18723	3.00e-09	2.06e-07	131
GO:0045921	Colorectum	AD	positive regulation of exocytosis	33/3918	86/18723	1.58e-04	2.20e-03	33
GO:0045785	Colorectum	AD	positive regulation of cell adhesion	122/3918	437/18723	2.65e-04	3.28e-03	122
GO:0051047	Colorectum	AD	positive regulation of secretion	90/3918	310/18723	4.11e-04	4.66e-03	90
GO:1903532	Colorectum	AD	positive regulation of secretion by cell	82/3918	282/18723	6.85e-04	7.00e-03	82
GO:0006887	Colorectum	AD	exocytosis	96/3918	352/18723	2.48e-03	1.90e-02	96
GO:1903706	Colorectum	AD	regulation of hemopoiesis	99/3918	367/18723	3.08e-03	2.28e-02	99
GO:0017157	Colorectum	AD	regulation of exocytosis	59/3918	202/18723	3.20e-03	2.36e-02	59
GO:0120162	Colorectum	AD	positive regulation of cold-induced thermogenesis	32/3918	97/18723	3.74e-03	2.63e-02	32
GO:0106106	Colorectum	AD	cold-induced thermogenesis	43/3918	144/18723	7.05e-03	4.31e-02	43
GO:0120161	Colorectum	AD	regulation of cold-induced thermogenesis	43/3918	144/18723	7.05e-03	4.31e-02	43
GO:1990845	Colorectum	AD	adaptive thermogenesis	46/3918	157/18723	7.97e-03	4.73e-02	46
GO:00516561	Colorectum	SER	establishment of organelle localization	100/2897	390/18723	1.11e-07	6.79e-06	100
GO:00457851	Colorectum	SER	positive regulation of cell adhesion	93/2897	437/18723	6.78e-04	9.04e-03	93
GO:0007162	Colorectum	SER	negative regulation of cell adhesion	68/2897	303/18723	8.02e-04	1.01e-02	68
GO:00459211	Colorectum	SER	positive regulation of exocytosis	25/2897	86/18723	9.88e-04	1.17e-02	25
GO:00068871	Colorectum	SER	exocytosis	75/2897	352/18723	2.05e-03	2.03e-02	75
GO:00510471	Colorectum	SER	positive regulation of secretion	65/2897	310/18723	5.71e-03	4.19e-02	65
GO:0022408	Colorectum	SER	negative regulation of cell-cell adhesion	44/2897	196/18723	6.08e-03	4.42e-02	44
GO:00171571	Colorectum	SER	regulation of exocytosis	45/2897	202/18723	6.46e-03	4.63e-02	45

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04151	Colorectum	FAP	PI3K-Akt signaling pathway	75/1404	354/8465	1.23e-02	4.19e-02	2.55e-02	75
hsa041511	Colorectum	FAP	PI3K-Akt signaling pathway	75/1404	354/8465	1.23e-02	4.19e-02	2.55e-02	75
hsa046599	Esophagus	ESCC	Th17 cell differentiation	68/4205	108/8465	3.53e-03	9.30e-03	4.76e-03	68
hsa046585	Esophagus	ESCC	Th1 and Th2 cell differentiation	58/4205	92/8465	6.49e-03	1.60e-02	8.19e-03	58
hsa041517	Esophagus	ESCC	PI3K-Akt signaling pathway	197/4205	354/8465	1.24e-02	2.83e-02	1.45e-02	197
hsa0465914	Esophagus	ESCC	Th17 cell differentiation	68/4205	108/8465	3.53e-03	9.30e-03	4.76e-03	68
hsa0465812	Esophagus	ESCC	Th1 and Th2 cell differentiation	58/4205	92/8465	6.49e-03	1.60e-02	8.19e-03	58
hsa0415114	Esophagus	ESCC	PI3K-Akt signaling pathway	197/4205	354/8465	1.24e-02	2.83e-02	1.45e-02	197
hsa046598	Oral cavity	OSCC	Th17 cell differentiation	65/3704	108/8465	4.02e-04	1.25e-03	6.35e-04	65
hsa041516	Oral cavity	OSCC	PI3K-Akt signaling pathway	185/3704	354/8465	6.26e-04	1.86e-03	9.49e-04	185
hsa046584	Oral cavity	OSCC	Th1 and Th2 cell differentiation	53/3704	92/8465	5.00e-03	1.20e-02	6.13e-03	53
hsa0465913	Oral cavity	OSCC	Th17 cell differentiation	65/3704	108/8465	4.02e-04	1.25e-03	6.35e-04	65
hsa0415113	Oral cavity	OSCC	PI3K-Akt signaling pathway	185/3704	354/8465	6.26e-04	1.86e-03	9.49e-04	185
hsa0465811	Oral cavity	OSCC	Th1 and Th2 cell differentiation	53/3704	92/8465	5.00e-03	1.20e-02	6.13e-03	53
hsa0465923	Oral cavity	EOLP	Th17 cell differentiation	41/1218	108/8465	9.84e-10	3.18e-08	1.87e-08	41
hsa0465821	Oral cavity	EOLP	Th1 and Th2 cell differentiation	31/1218	92/8465	2.27e-06	1.79e-05	1.05e-05	31
hsa053214	Oral cavity	EOLP	Inflammatory bowel disease	20/1218	65/8465	5.49e-04	2.16e-03	1.28e-03	20
hsa0415123	Oral cavity	EOLP	PI3K-Akt signaling pathway	73/1218	354/8465	7.03e-04	2.69e-03	1.59e-03	73
hsa04630	Oral cavity	EOLP	JAK-STAT signaling pathway	35/1218	166/8465	1.15e-02	3.07e-02	1.81e-02	35
hsa0465933	Oral cavity	EOLP	Th17 cell differentiation	41/1218	108/8465	9.84e-10	3.18e-08	1.87e-08	41

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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

IL4R

SNV

Missense_Mutation

c.971C>A

p.Pro324His

p.P324H

P24394

protein_coding

tolerated(0.21)

benign(0.187)

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

IL4R

SNV

Missense_Mutation

novel

c.352A>C

p.Ser118Arg

p.S118R

P24394

protein_coding

deleterious(0.04)

probably_damaging(0.993)

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IL4R

SNV

Missense_Mutation

novel

c.353G>C

p.Ser118Thr

p.S118T

P24394

protein_coding

deleterious(0.04)

possibly_damaging(0.578)

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IL4R

SNV

Missense_Mutation

c.293N>T

p.Asn98Ile

p.N98I

P24394

protein_coding

tolerated(0.29)

benign(0.003)

TCGA-A8-A091-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

IL4R

SNV

Missense_Mutation

c.761N>A

p.Ser254Asn

p.S254N

P24394

protein_coding

deleterious(0.02)

possibly_damaging(0.462)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IL4R

SNV

Missense_Mutation

novel

c.2143N>C

p.Ala715Pro

p.A715P

P24394

protein_coding

deleterious(0.01)

probably_damaging(0.946)

TCGA-AO-A1KT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

fluorouracil

IL4R

SNV

Missense_Mutation

c.2462A>G

p.Tyr821Cys

p.Y821C

P24394

protein_coding

tolerated(0.37)

benign(0)

TCGA-AR-A24S-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

anastrozole

IL4R

SNV

Missense_Mutation

novel

c.1805N>C

p.Gly602Ala

p.G602A

P24394

protein_coding

tolerated(0.05)

benign(0.07)

TCGA-B6-A0I8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

IL4R

SNV

Missense_Mutation

c.731T>A

p.Ile244Asn

p.I244N

P24394

protein_coding

deleterious(0)

probably_damaging(0.95)

TCGA-B6-A0IJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

IL4R

SNV

Missense_Mutation

c.2260N>T

p.Pro754Ser

p.P754S

P24394

protein_coding

tolerated(0.32)

benign(0.211)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

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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
3566	IL4R	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE		Hepatitis vaccines		21111021
3566	IL4R	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE		PRX-321	PRX-321
3566	IL4R	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE		CHEMBL2108583	CINTREDEKIN BESUDOTOX
3566	IL4R	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE		AIR645
3566	IL4R	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE		SAR-156597	ROMILKIMAB
3566	IL4R	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE		Aerovant
3566	IL4R	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE		CINTREDEKIN BESUDOTOX
3566	IL4R	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE		AER001,AEROVANT
3566	IL4R	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE	antibody	223365910	DUPILUMAB
3566	IL4R	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE		pitrakinra	PITRAKINRA

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