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: CRABP2

Gene summary for CRABP2

Gene summary.

Gene information	Species	Human
	Gene symbol	CRABP2
	Gene ID	1382
	Gene name	cellular retinoic acid binding protein 2
	Gene Alias	CRABP-II
	Cytomap	1q23.1
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	P29373

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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
1382	CRABP2	GSM4909281	Human	Breast	IDC	2.46e-02	-3.33e-01	0.21
1382	CRABP2	GSM4909282	Human	Breast	IDC	4.59e-31	6.86e-01	-0.0288
1382	CRABP2	GSM4909285	Human	Breast	IDC	3.22e-53	8.42e-01	0.21
1382	CRABP2	GSM4909287	Human	Breast	IDC	7.06e-10	-5.19e-01	0.2057
1382	CRABP2	GSM4909288	Human	Breast	IDC	5.71e-08	-7.66e-01	0.0988
1382	CRABP2	GSM4909289	Human	Breast	IDC	5.60e-13	8.41e-01	0.1064
1382	CRABP2	GSM4909290	Human	Breast	IDC	2.00e-20	-7.49e-01	0.2096
1382	CRABP2	GSM4909293	Human	Breast	IDC	7.13e-05	1.68e-01	0.1581
1382	CRABP2	GSM4909294	Human	Breast	IDC	3.66e-03	-3.54e-01	0.2022
1382	CRABP2	GSM4909297	Human	Breast	IDC	1.97e-15	3.10e-01	0.1517
1382	CRABP2	GSM4909298	Human	Breast	IDC	8.69e-07	3.09e-01	0.1551
1382	CRABP2	GSM4909304	Human	Breast	IDC	1.58e-37	-8.29e-01	0.1636
1382	CRABP2	GSM4909305	Human	Breast	IDC	2.12e-02	3.22e-01	0.0436
1382	CRABP2	GSM4909306	Human	Breast	IDC	1.95e-39	7.26e-01	0.1564
1382	CRABP2	GSM4909307	Human	Breast	IDC	4.43e-46	8.19e-01	0.1569
1382	CRABP2	GSM4909308	Human	Breast	IDC	1.50e-51	8.52e-01	0.158
1382	CRABP2	GSM4909311	Human	Breast	IDC	1.19e-19	2.20e-02	0.1534
1382	CRABP2	GSM4909315	Human	Breast	IDC	4.93e-09	-5.47e-01	0.21
1382	CRABP2	GSM4909319	Human	Breast	IDC	5.79e-41	3.14e-01	0.1563
1382	CRABP2	GSM4909320	Human	Breast	IDC	4.99e-13	5.80e-01	0.1575

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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
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
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:0035113	Endometrium	AEH	embryonic appendage morphogenesis	23/2100	116/18723	4.58e-03	2.95e-02	23
GO:00085447	Endometrium	AEH	epidermis development	52/2100	324/18723	5.00e-03	3.14e-02	52
GO:0035115	Endometrium	AEH	embryonic forelimb morphogenesis	9/2100	31/18723	5.59e-03	3.44e-02	9
GO:00507725	Endometrium	AEH	positive regulation of axonogenesis	17/2100	79/18723	5.93e-03	3.59e-02	17
GO:0035136	Endometrium	AEH	forelimb morphogenesis	10/2100	38/18723	7.62e-03	4.31e-02	10
GO:00507677	Endometrium	AEH	regulation of neurogenesis	56/2100	364/18723	8.87e-03	4.82e-02	56
GO:006156412	Endometrium	EEC	axon development	93/2168	467/18723	9.60e-08	4.69e-06	93
GO:001604915	Endometrium	EEC	cell growth	95/2168	482/18723	1.16e-07	5.54e-06	95
GO:003253516	Endometrium	EEC	regulation of cellular component size	79/2168	383/18723	1.98e-07	8.93e-06	79
GO:006056013	Endometrium	EEC	developmental growth involved in morphogenesis	54/2168	234/18723	4.60e-07	1.78e-05	54
GO:000740912	Endometrium	EEC	axonogenesis	82/2168	418/18723	1.03e-06	3.49e-05	82
GO:000155814	Endometrium	EEC	regulation of cell growth	77/2168	414/18723	1.64e-05	3.16e-04	77
GO:004858813	Endometrium	EEC	developmental cell growth	49/2168	234/18723	2.59e-05	4.56e-04	49
GO:001097513	Endometrium	EEC	regulation of neuron projection development	79/2168	445/18723	6.80e-05	1.01e-03	79
GO:000836111	Endometrium	EEC	regulation of cell size	39/2168	181/18723	8.72e-05	1.24e-03	39
GO:001072012	Endometrium	EEC	positive regulation of cell development	56/2168	298/18723	1.68e-04	2.10e-03	56
GO:004863812	Endometrium	EEC	regulation of developmental growth	58/2168	330/18723	7.65e-04	7.16e-03	58
GO:003134613	Endometrium	EEC	positive regulation of cell projection organization	61/2168	353/18723	8.82e-04	8.03e-03	61
GO:003510711	Endometrium	EEC	appendage morphogenesis	29/2168	138/18723	1.01e-03	8.89e-03	29
GO:003510811	Endometrium	EEC	limb morphogenesis	29/2168	138/18723	1.01e-03	8.89e-03	29

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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

CRABP2

SNV

Missense_Mutation

novel

c.379G>A

p.Asp127Asn

p.D127N

P29373

protein_coding

tolerated(0.07)

probably_damaging(0.924)

TCGA-C5-A8ZZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unspecific

Cisplatin

CRABP2

SNV

Missense_Mutation

rs757917252

c.412G>C

p.Glu138Gln

p.E138Q

P29373

protein_coding

tolerated(0.09)

benign(0.042)

TCGA-DY-A1DC-01

Colorectum

rectum adenocarcinoma

Female

>=65

I/II

Chemotherapy

capecitabine

CRABP2

SNV

Missense_Mutation

novel

c.124N>A

p.Val42Met

p.V42M

P29373

protein_coding

deleterious(0.03)

probably_damaging(0.981)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

CRABP2

SNV

Missense_Mutation

c.98N>A

p.Ala33Asp

p.A33D

P29373

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

CRABP2

SNV

Missense_Mutation

rs548565052

c.179G>A

p.Arg60His

p.R60H

P29373

protein_coding

deleterious(0)

possibly_damaging(0.857)

TCGA-AP-A0LP-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Hormone Therapy

megace

CRABP2

SNV

Missense_Mutation

c.51N>T

p.Glu17Asp

p.E17D

P29373

protein_coding

tolerated(0.35)

benign(0.003)

TCGA-AX-A0J0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CRABP2

SNV

Missense_Mutation

novel

c.317C>T

p.Pro106Leu

p.P106L

P29373

protein_coding

tolerated(0.07)

probably_damaging(1)

TCGA-B5-A1MX-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Hormone Therapy

megace

CRABP2

SNV

Missense_Mutation

rs548565052

c.179G>A

p.Arg60His

p.R60H

P29373

protein_coding

deleterious(0)

possibly_damaging(0.857)

TCGA-D1-A163-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

taxol

CRABP2

SNV

Missense_Mutation

novel

c.13N>C

p.Ser5Pro

p.S5P

P29373

protein_coding

deleterious(0.01)

possibly_damaging(0.81)

TCGA-D1-A2G0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CRABP2

SNV

Missense_Mutation

novel

c.92A>T

p.Lys31Met

p.K31M

P29373

protein_coding

deleterious(0.04)

possibly_damaging(0.449)

TCGA-CC-A5UD-01

Liver

liver hepatocellular carcinoma

Male

<65

III/IV

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
1382	CRABP2	NA		RETINOID		12153175
1382	CRABP2	NA		BESTATIN METHYL ESTER	BESTATIN METHYL ESTER	21515062

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